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June 15, 2012
SUPPLEMENT TO
www.revoptom.com
Joseph W. Sowka, O.D., F.A.A.O., Dipl.
001_ro0612_hndbk.indd 1
Andrew S. Gurwood, O.D., F.A.A.O., Dipl.
Alan G. Kabat, O.D., F.A.A.O.
6/1/12 2:54 PM
TABLE OF CONTENTS
Eyelids & Adnexa
Conjunctiva & Sclera
Cornea
EYELIDS & ADNEXA
Uvea & Glaucoma
Vitreous & Retina
Neuro-Ophthalmic Disease
UVEA & GLAUCOMA
Basal Cell Carcinoma .......................................... 4
Acute Angle Closure Glaucoma ........................... 31
Chalazion .......................................................... 5
Pars Planitis ....................................................... 34
Dermatochalasis and Blepharochalasis ................... 7
Steroid-Induced Glaucoma .................................. 36
Hordeolum .......................................................... 9
Hyphema .......................................................... 38
Phthiriasis Palpebrarum....................................... 11
Diurnal Control of Intraocular Pressure .................. 41
CONJUNCTIVA & SCLERA
VITREOUS & RETINA
Episcleritis ......................................................... 13
Diabetic Retinopathy .......................................... 42
Scleritis ............................................................. 14
Central Serous Chorioretinopathy ........................ 44
Superior Limbic Keratoconjunctivitis...................... 16
Retinal Detachment............................................. 47
Toxic Conjunctivitis............................................. 18
Retinal Pigment Epithelial (RPE) Detachment .......... 51
Vernal Keratoconjunctivitis .................................. 21
Retinitis Pigmentosa ............................................ 53
CORNEA
NEURO-OPHTHALMIC DISEASE
Contact Lens-Associated Acute Red Eye
Arteritic Anterior Ischemic Optic Neuropathy
(CLAARE) .......................................................... 23
(AAION) ........................................................... 57
Disciform Keratitis ............................................. 24
Non-Arteritic Anterior Ischemic Optic
Fungal Keratitis .................................................. 26
Neuropathy (NAAION) ...................................... 59
Lattice Corneal Dystrophy ................................... 28
Benign Episodic Pupillary Mydriasis ..................... 62
The ABCs of Corneal Surgery .............................. 30
Duane’s Retraction Syndrome .............................. 63
Horner’s Syndrome ............................................ 65
A Peer-Reviewed Supplement
The articles in this supplement were subjected to Review of Optometry ’s peer-review process. The magazine
employs a double-blind review system for clinical manuscripts. Two clinical experts review each manuscript
before publication. This supplement was edited by the Review of Optometry staff.
©2012. Reproducing editorial content and photographs requires permission from Review of Optometry®.
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JUNE 15, 2012
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FROM THE AUTHORS
To our Colleagues:
Optometry has evolved from what was once a purely visual correction and refractive drugless profession to an
integrated member of the health care team. Therapeutic management of ocular disease has been a part of optometry for many years, but this has not always been so. It was the forward thinking of one of our mentors, Dr. Lou
Catania that pioneered optometry into the therapeutic arena. As students of his, we have endeavored through the
publication of The Handbook of Ocular Disease Management to continue and advance Dr. Catania’s work by providing a concise, peer-reviewed, evidence-based compendium designed to give fellow colleagues a quick reference
when practicing therapeutic optometry. We can all thank Dr. Catania for our ability to treat patients therapeutically.
There always exists the need for optometrists to remain current and enhance their knowledge and education.
Optometrists must commit to lifelong learning. Reading high-quality, peer-reviewed publications is necessary.
Attending continuing education conferences that are free of commercial bias allows optometrists to keep current
and interact, both socially and professionally, with colleagues. We have always felt that the best way to begin this
commitment to lifelong learning is through the completion of an accredited residency. Residency training not only
provides increased clinical experience, it opens doors and initiates the lifelong learning process. To all optometry
students (and practitioners) reading this manuscript, we strongly encourage you to pursue residency training.
We hope that you enjoy the fourteenth edition of The Handbook of Ocular Disease Management.
Joe, Andy and Al
Joseph W. Sowka, O.D., F.A.A.O., Dipl., is a professor of optometry at Nova
Southeastern University College of Optometry, where he teaches glaucoma and
retinal disease. Dr. Sowka is the director of the Glaucoma Service and chief of the
Advanced Care Service. He is a diplomate of the Disease Section of the American
Academy of Optometry (Glaucoma Subsection) and a founding member of the
Optometric Glaucoma Society and the Optometric Retina Society. He can be reached
at (954) 262-1472 or at [email protected]
Andrew S. Gurwood, O.D., F.A.A.O., Dipl., is a member of the attending staff of Albert
Einstein Medical Center’s Department of Ophthalmology. Involved in direct patient
care, he also precepts students and medical residents teaching clinical practice, clinical
medicine and its relationship to the eye and ocular urgencies and emergencies. He is a
diplomate of the American Academy of Optometry’s Primary Care Section, a founding
member of the Optometric Retina Society, a member of the Optometric Glaucoma
Society and the Dry Eye Society. Dr. Gurwood serves on the American Academy of
Optometry’s Program Committee and is the Chairperson of the American Academy of
Optometry’s Disease Section Written Examination for Retinal Disease Diplomate. He
can be reached at (215) 276-6134 or at [email protected]
Alan G. Kabat, O.D., F.A.A.O., is an associate professor at Nova Southeastern
University College of Optometry, where he teaches several courses in ocular disease
management and clinical procedures. He also serves as an attending physician in the
Primary Care Service of The Eye Care Institute. A recognized expert in the area of
ocular surface disease, Dr. Kabat is a founding member of both the Optometric Dry
Eye Society and the Ocular Surface Society of Optometry. He can be reached at
(954) 262-1440 or at [email protected]
]
The authors have
no direct financial
interest in any
product mentioned.
This publication addresses the management of various conditions with support from the best available peer-reviewed literature. This is
done to provide the most up-to-date management of patients with various conditions and to indicate when patient referral is appropriate. In many cases, the management may necessitate treatment from a specialist or sub-specialist. This manuscript does not recommend
that any doctor practice beyond the scope of licensure or level of personal comfort. It is up to the reader to understand the scope of state
licensure and practice only within those guidelines.
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EYELIDS AND ADNEXA
BASAL CELL CARCINOMA
Signs and Symptoms
Basal cell carcinoma (BCC) is the
most common cutaneous neoplasm
in humans. It is also the most frequently seen periocular malignancy in
clinical practice.1-4 BCC is typically
found on the body in regions that
are directly exposed to sunlight; thus,
these lesions are often observed about
the head and neck, especially in the
vicinity of the eyelid and nose.5 This
tumor often presents as a cosmetic
concern for patients (particularly
those with a previous history of skin
cancer); however, it may occasionally
be discovered upon routine biomicroscopic evaluation. There is usually no
associated pain or discomfort in the
early stages. BCC is typically encountered in older, fair-skinned individuals, many of whom offer a history of
prolonged or excessive exposure to
sunlight.3 The lower lid margin and
medial canthus appear to be the most
frequently involved sites.4 Men also
appear to be affected more commonly
than women.5
Clinically, BCCs may be classified
into at least four groups: (1) localized (nodular, ulcerative); (2) diffuse
(morpheaform, sclerosing); (3) superficial multifocal; and (4) fibroepithelioma of Pinkus.5,6 Of these, the
nodular and ulcerative varieties are
most prevalent and recognized as the
“classic” presentations.1-6 The nodular
form appears as a small, translucent, raised area with poorly defined
edges, which is firm to the touch.
Over time, nodular lesions may
develop telangiectatic vessels along
the surface, and the inner portion
may atrophy. This creates a “pearly,”
indurated (firm) outer margin with
an excavated center, giving rise to the
classic ulcerative presentation.
The sclerosing or morpheaform
variety accounts for only about
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Basal cell carcinoma. Note the characteristic
“pearly” appearance and raised, rolled borders.
6% of all BCCs, and presents as a
firm, pale, waxy yellow plaque with
indistinct borders.5,7 The superficial multifocal form of BCC is
also uncommon; it appears as wellcircumscribed, red scaly patches
with pearly borders, interspersed
between areas of normal skin.5
Fibroepithelioma of Pinkus presents
as a sessile (broad-based), flesh-colored mass, whose histologic appearance closely resembles BCC. These
lesions are almost exclusively found
in the lumbosacral area.5,8
Pathophysiology
The etiology and pathogenesis of
BCC is not entirely known, but current research supports the likelihood
of a genetic mutation that is triggered
by certain environmental factors.9 The
most significant of these risk factors
appears to be exposure to ultraviolet radiation, followed by increasing
age.7,9 In addition, Caucasians (particularly those with Celtic ancestry,
e.g. Irish, Scottish and Welsh) have
a significantly greater incidence of
developing BCC than other races.9
Those individuals at greatest risk are
labeled as skin type 1 (“always burns,
never tans”).9 A positive family history
of BCC, immunosuppressive therapy,
exposure to certain toxins (e.g. arsenic
and coal tar derivatives) and irradiation are additional risk factors.1,5,7,9
In the vast majority of cases, the
progression of BCC is exceedingly
slow; lesions often develop over the
course of years, rather than weeks
or months. Metastasis is also very
infrequent, with a rate documented
between 0.0028% and 0.55%.9 The
larger lesions have a greater propensity for metastasis.1 Despite favorable
statistics, clinicians must realize that
all BCCs possess the propensity to
invade deeper structures and ultimately metastasize if they do not
receive definitive treatment in a
timely manner.9
Management
A wide range of surgical and
non-surgical treatment options are
available for BCC. Generally, surgical resection is regarded as the
treatment of choice for periocular
malignancies.10 To diminish the
likelihood of recurrence, control of
the surgical margins is crucial. There
are two techniques used for microscopic margin control: traditional
frozen-section controlled excision
and Mohs micrographic surgery.10-15
Both of these techniques are associated with a low reported recurrence
rate.10-15 Frozen-section controlled
excision has historically employed
3mm to 4mm margins, although
newer surgical procedures may be
able to accomplish similar outcomes
with only 1mm to 2mm margins.10-11
Mohs micrographic surgery involves
serial removal of the affected tissue
with progressive, real-time histologic
evaluation of the margins; it is considered the surgical treatment of first
choice for primary facial BCCs.12,13
Opponents of the Mohs technique
for periocular BCC cite the fact that
it is costly and time-consuming, and
can result in irregular margins that
complicate reconstruction.10
Non-surgical therapies may be
utilized in several instances: (1) as
adjunctive therapy to surgery; (2) in
those instances where the lesions are
JUNE 15, 2012
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Clinical Pearls
• BCC constitutes approximately
75% to 80% of non-melanoma skin
cancers. If an eye care practitioner diagnoses any periocular malignancy during
his or her career, the odds are favorable
that it will be BCC.5
• As important as therapeutic
intervention is for confirmed BCC,
preventive measures are even more
crucial for at-risk individuals. At-risk
patients (fair-skinned, older age,
history of skin cancer in family)
should be advised to avoid excessive sun exposure and employ topical
sunscreen while wearing appropriate
clothing whenever spending time in
high UV conditions.
• Both duration and intensity of
UV light exposure seem to be important in the development of BCC.
Hence, the effect is not necessarily cumulative; an individual with a
few instances of excessive UV light
exposure may be of equal or greater
risk than someone with a lifetime of
modest UV light exposure.
• BCC is rarely life threatening
because of its non-metastatic, slow-
growing nature. However, the tumor
does possess the capacity, over time,
to cause significant local destruction,
and should always be treated appropriately and aggressively.
• Early biopsy is the key to diagnosis in any malignancy. Suspicious
lid lesions that demonstrate irregular
growth, changes in color or appearance, or discharge of a purulent or
bloody nature that do not heal should
be biopsied to rule out cancerous
etiologies. Confirmed malignancies
should be referred promptly for treatment to an oculoplastic specialist or,
when possible, an ocular oncologist.
• The ABCDEs apply:
Asymmetry of the lesion, Borders
which are irregular, Coloration that
is abnormally dark or speckled,
Diameters of 6mm or more (greater
than the diameter of a pencil eraser)
and Elevation with any changes over
time of any of the aforementioned
should be treated with suspicion.
1. Crowson AN. Basal cell carcinoma: biology,
morphology and clinical implications. Mod Pathol.
2006;19; Suppl 2:S127-47.
2. Prabhakaran VC, Gupta A, Huilgol SC, Selva
D. Basal cell carcinoma of the eyelids. Compr
Ophthalmol Update. 2007;8(1):1-14.
3. Cook BE Jr, Bartley GB. Treatment options and
future prospects for the management of eyelid malignancies: an evidence-based update. Ophthalmology.
2001;108(11):2088-98.
4. Soysal HG, Soysal E, Markoç F, Ardiç F. Basal
cell carcinoma of the eyelids and periorbital region in
a Turkish population. Ophthal Plast Reconstr Surg.
2008;24(3):201-6.
5. Nakayama M, Tabuchi K, Nakamura Y, Hara A.
Basal cell carcinoma of the head and neck. J Skin
Cancer. 2011;2011:496910. Epub 2010 Dec 15.
6. Riedel KG, Beyer-Machule CK. Basal cell carcinoma. In: Albert DM, Jakobiec FA, eds. Principles and
Practice of Ophthalmology, 2nd edition. Philadelphia:
WB Saunders, 2000. 3361-5.
7. Scrivener Y, Grosshans E, Cribier B. Variations
of basal cell carcinomas according to gender,
age, location and histopathological subtype. Br J
Dermatol. 2002;147(1):41-7.
8. Strauss RM, Edwards S, Stables GI. Pigmented
fibroepithelioma of Pinkus. Br J Dermatol. 2004;
150(6):1208-9.
9. Wong CSM, Strange RC, Lear JT. Basal cell carcinoma. BMJ. 2003;327(7418):794-8.
10. Levin F, Khalil M, McCormick SA, et al. Excision
of periocular basal cell carcinoma with stereoscopic
microdissection of surgical margins for frozen-section
control: report of 200 cases. Arch Ophthalmol.
EYELIDS AND ADNEXA
extensive, and surgery is not appropriate; (3) when patients are too
physically compromised to withstand
surgery; or (4) when patients simply
refuse surgery. Options may include
laser cautery, external beam irradiation, cryotherapy with liquid nitrogen, photodynamic therapy with
δ-aminolevulinic acid, topical
Efudex (5% fluorouracil, Valeant
Pharmaceuticals) and topical
Aldara (5% imiquimod, Graceway
Pharmaceuticals).10,14 Recent studies have shown imiquimod to be
an attractive alternative for small,
nodular periocular BCC; this agent
appears to offer a cure rate similar
to surgical excision while preserving
cosmesis and avoiding the emotional
trauma associated with surgery.16,17
2009;127(8):1011-5.
11. Hsuan JD, Harrad RA, Potts MJ, Collins C. Small
margin excision of periocular basal cell carcinoma: 5
year results. Br J Ophthalmol. 2004;88(3):358-60.
12. Smeets NW, Krekels GA, Ostertag JU, et al.
Surgical excision vs Mohs micrographic surgery for
basal-cell carcinoma of the face: Randomised controlled trial. Lancet. 2004;364(9447):1766-72.
13. Smeets NW, Kuijpers DI, Nelemans P, et al.
Mohs’ micrographic surgery for treatment of basal
cell carcinoma of the face – results of a retrospective study and review of the literature. Br J Dermatol.
2004;151(1):141-7.
14. Wong VA, Marshall JA, Whitehead KJ, et al.
Management of periocular basal cell carcinoma with
modified en face frozen section controlled excision.
Ophthal Plast Reconstr Surg. 2002;18(6):430-5.
15. Conway RM, Themel S, Holbach LM. Surgery
for primary basal cell carcinoma including the eyelid
margins with intraoperative frozen section control:
comparative interventional study with a minimum
clinical follow up of 5 years. Br J Ophthalmol.
2004;88(2):236-8.
16. Carneiro RC, de Macedo EM, Matayoshi S.
Imiquimod 5% cream for the treatment of periocular
Basal cell carcinoma. Ophthal Plast Reconstr Surg.
2010;26(2):100-2.
17. Garcia-Martin E, Idoipe M, Gil LM, et al. Efficacy
and tolerability of imiquimod 5% cream to treat periocular basal cell carcinomas. J Ocul Pharmacol Ther.
2010;26(4):373-9.
CHALAZION
Signs and Symptoms
Chalazia typically present as one
or more focal, firm, painless nodules in the upper or lower eyelid.1-7
While many patients seek care
because of the cosmetic concern,
some cases with larger lesions may
produce mechanical ptosis resulting
in some degree of obstructed vision.
Still, in some instances, patients
may be unaware of their presence.
The lesions do not cause discomfort,
though a history of painful lid infection such as a hordeolum or preseptal cellulitis prior to its discovery, is
possible.1 Enlargement of the lesion
over time is possible. Often, there is
a history of concurrent blepharitis,
usually in the form of meibomian
gland obstruction/dysfunction.1-7
In some patients, chalazia may be
recurrent and indicative of chronic
blepharitis, lid hygiene issues, acne
rosacea or, in rare cases, meibomian
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Chalazion—external view (left) and everted (right).
gland or sebaceous cell carcinoma.5
Men appear to be affected somewhat
more often than women.8
Pathophysiology
Chalazia are the most common
inflammatory lesions of the eyelid.1,4-6 Chalazia are non-infectious
and sterile, representing a lipogranulomatous inflammation of the
sebaceous meibomian gland(s).4
The typical etiology is obstruction
of meibomian ducts with resultant
retention of glandular secretions.4
This frequently occurs in cases of
chronic posterior blepharitis.2,7,8
Occasionally, chalazia form from
the collection of inflammatory cells
following eyelid infection such as
a hordeolum or preseptal cellulitis;
this is referred to as a secondary
chalazion.2
Histological evaluation of the
chalazion reveals an inert collection
of corticosteroid-sensitive histiocytes, multinucleated giant cells,
plasma cells, polymorphonuclear
leukocytes and eosinophils.7,8 The
nodule is encapsulated by connective
tissue, often interdigitating with the
tarsal plate.
Management
In cases not exhibiting concurrent
infection, the use of oral antibiotics is unnecessary. While chalazia
do respond to anti-inflammatory
therapy, the anatomically deep
nature of this condition renders a
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topical medication strategy virtually ineffective. Nevertheless, warm
compresses (to clear the meibomian
ducts of stagnant oils), accompanied
by gentle digital massage (to rupture and express the nodule), can be
attempted on a t.i.d to q.i.d. basis
for lesions discovered early in their
process (less than three weeks old).912 Unfortunately, this therapy tends
to be ineffective, with less than 25%
of lesions resolving spontaneously or
with hot compresses.9-12
Chalazia that do not respond to
conservative therapy can be treated
with excision or intralesional corticosteroid injection.10,13-17 Studies document a success rate of approximately
80% to 90% using intralesional
injection.10,13-17 Using a standard 1cc
tuberculin syringe and 30-gauge needle, 0.1ml to 0.3ml of triamcinolone
acetonide 10mg/ml (Kenalog-10,
Bristol Myers Squibb) or 40mg/
ml (Kenalog-40) is injected directly
into the lesion. The approach should
preferably be from the palpebral side,
because eyelid skin depigmentation
may occur when the injection occurs
on the dermal side.17 This side effect
is more common in dark-skinned
individuals.17 The use of a chalazion
clamp and topical anesthesia may be
helpful, but is not absolutely necessary.15 One recent report documented
adequate anesthesia with topical
lidocaine gel only. The end result of
the study produced equivocal success
compared to procedures with stan-
dard injectable anesthesia.6 Patients
usually demonstrate marked improvement within one week of initial treatment, though repeat injections may
be necessary for larger chalazia.12-17
Should intralesional steroid injections
prove ineffective or if the patient
cannot tolerate the procedure, surgical curettage under local anesthesia is
indicated.
Finally, recurrent multiple giant
chalazia have been recognized as an
ophthalmic feature of Job’s syndrome
(hyperimmunoglobulin E with connective tissue, skeletal and immunologic abnormalities).18,19 In addition
to meibomian gland/sebaceous cell
carcinoma, this unusual syndrome
should be suspected in cases where
recurrent giant chalazia are documented, regardless of the patient’s
age.18 Measurement of serum IgE
and eosinophils is essential to establish a proper diagnosis.18
Clinical Pearls
• While vision problems are
uncommon with chalazia, large
lesions may cause a mechanical ptosis
and resultant obscuration of the vertical visual field. For this reason, it
is important to treat chalazia aggressively in young children. Obscuration
of the visual field in the young has
been documented to produce a
deprivational amblyopia. Also, the
induced chronic external pressure
produced by larger lesions has the
capability of inducing alterations in
corneal curvature; several cases of
chalazion-induced astigmatism have
been documented.20,21
• Patients with chalazia should be
cautioned against vigorous massage of
the involved area. While gentle massage is beneficial, vigorous massage
may cause further extravasation of the
granulomatous inflammation into the
surrounding tissue and exacerbation
or complication of the condition.
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1. Aurora AL, Blodi FC. Lesions of the eyelids: A
clinicopathological study. Surv Ophthalmol. 1970;
15(2):94-104.
2. Lindsley K, Nichols JJ, Dickersin K. Interventions
for acute internal hordeolum. Cochrane Database
Syst Rev. 2010;(9):CD007742.
3. Aglianó M, Lorenzoni P, Volpi N, et al. Lymphatic
vessels in human eyelids: an immunohistological
study in dermatochalasis and chalazion. Lymphology.
2008;41(1):29-39.
4. Dhaliwal U, Bhatia A. A rationale for therapeutic
decision-making in chalazia. Orbit. 2005;24(4):22730.
5. Scat Y, Liotet S, Carre F. Epidemiological study
of benign tumors and inflammatory pseudotumors
of the eye and its adnexa. J Fr Ophthalmol. 1996;
19(8-9):514-9.
6. Ozdal PC, Codere F, Callejo S, et al. Accuracy
of the clinical diagnosis of chalazion. Eye. 2004;
18(2):135-8.
7. Lederman C, Miller M. Hordeola and chalazia.
Pediatr Rev. 1999;20(8):283-4.
8. Gupta N, Dhawan A, Beri S, D’souza P. Clinical
spectrum of pediatric blepharokeratoconjunctivitis. J
AAPOS. 2010;14(6):527-9.
9. Cottrell DG, Bosanquet RC, Fawcett IM.
Chalazions: the frequency of spontaneous resolution.
Br Med J (Clin Res Ed). 1983; 287(6405):1595.
10. Goawalla A, Lee VA. Prospective randomized
treatment study comparing three treatment options
for chalazia: triamcinolone acetonide injections, incision and curettage and treatment with hot compresses. Clin Experiment Ophthalmol. 2007;35(8):706-12.
EYELIDS AND ADNEXA
• Many practitioners consider
intralesional steroid injection to be
contraindicated in dark-skinned individuals because of the risk of local
skin depigmentation. These blemishes can persist for months or may be
permanent. While injecting through
the palpebral conjunctiva diminishes
the risk, the side effect remains a
possibility.
• Recurrent chalazia, especially
those that recur in the same location
within the same lid after surgical
excision or lesions associated with
madarosis, warrant excisional biopsy.5 The greatest concern in these
cases is sebaceous gland carcinoma.5
This is an extremely aggressive form
of eyelid malignancy, which carries a high mortality rate and great
propensity toward metastasis. The
majority of misdiagnosed recurrent
chalazia represent sebaceous gland
carcinomas; however, other significant lesions include BCC and pyogenic granuloma.6,7
Dermatochalasis.
11. Garrett GW, Gillespie ME, Mannix BC.
Adrenocorticosteroid injection vs. conservative
therapy in the treatment of chalazia. Ann Ophthalmol.
1988;20(5):196-8.
12. Honda M, Honda K. Spontaneous resolution of
chalazion after 3 to 5 years. Eye Contact Lens. 2010
Jul;36(4):230-2.
13. Mohan K, Dhir SP, Munjal VP, Jain IS. The use
of intralesional steroids in the treatment of chalazion.
Ann Ophthalmol. 1986;18(4):158-60.
14. Ho SY, Lai JS. Subcutaneous steroid injection
as treatment for chalazion: prospective case series.
Hong Kong Med J. 2002;8(1):18-20.
15. Ben Simon GJ, Huang L, Nakra T, et al.
Intralesional triamcinolone acetonide injection for
primary and recurrent chalazia: is it really effective?
Ophthalmology 2005; 2(5):913-7.
16. Osayande OO, Mahmoud AO, Bolaji BO.
Comparison of topical lidocaine [2% gel] and injectable lidocaine [2% solution] for incision and curettage
of chalazion in Ilorin, Nigeria. Niger Postgrad Med J.
2010;17(4):270-6.
17. Ben Simon GJ, Rosen N, Rosner M, et al.
intralesional triamcinolone acetonide injection versus incision and curettage for primary chalazia: a
prospective, randomized study. Am J Ophthalmol.
2011;151(4):714-718.
18. Patteri P, Serru A, Chessa ML, et al. Recurrent
giant chalazia in hyperimmunoglobulin E (Job’s) syndrome. Int Ophthalmol. 2009;29(5):415-7.
19. Incecik F, Hergüner MO, Altunba ak S, Yilmaz M.
Pseudotumor cerebri in a child with hyperimmunoglobulin E syndrome. Turk J Pediatr. 2010;52(5):546-7.
20. Nisted M, Hofstetter HW. Effect of chalazion
on astigmatism. Am J Optom Physiol Opt. 1974;
51(8):579-82.
21. Cosar CB, Rapuano CJ, Cohen EJ, Laibson
PR. Chalazion as a cause of decreased vision after
LASIK. Cornea. 2001;20(8):890-2.
DERMATOCHALASIS &
BLEPHAROCHALASIS
Signs and Symptoms
Dermatochalasis describes a common, physiologic condition seen
clinically as sagging of the upper eyelids, and to some degree, the lower
lids. It is typically bilateral and most
often seen in patients ages 50 years
or older. The condition is progressive
and may be noted to a lesser degree
in younger individuals. Inspection of
the patient’s lids reveals redundant,
lax skin with poor adhesion to the
underlying muscle and connective tissue. An excess flap or fold of skin in
the upper lid is characteristic, and the
normal upper lid crease may be lost.
When the skin fold drapes over the
eyelashes, the term “hooding” is used.
Dermatochalasis typically results in a
ptosis, though patients may employ
the frontalis muscle to pull the lids
open; this action eliminates the ptosis but results in furrowing of the
forehead, as well as potential fatigue
and headaches in the frontal region.1
Additional clinical signs may include
upper eyelid entropion, lower eyelid
ectropion, blepharitis or dermatitis.1
Most commonly, dermatochalasis
presents as a simple cosmetic concern. Patients complain of “droopy
eyelids” that make them appear
older. However, some patients report
true functional difficulties, the most
common being obstruction of the
superior and/or peripheral aspect of
the visual field.1-3 Less commonly,
patients may complain of ocular irritation secondary to misdirected lashes
or chronic blepharitis.
Dermatochalasis is sometimes confused with blepharochalasis. Though
similar in nomenclature, these two
disorders are quite different in presentation and etiology. Blepharochalasis
is a rare condition that is characterized
by recurrent bouts of painless eyelid
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Blepharochalasis.
edema, each instance of which may
persist for several days.4 It typically
affects only the upper eyelids, and
may be unilateral or bilateral.5,6 Most
commonly, the onset occurs during
puberty, with the majority of patients
being adolescents and young adults.4,5
Inspection can reveal a variety of findings, depending upon the stage of the
disease. Most sources recognize three
stages of blepharochalasis.7 Stage 1,
the edema stage, presents with the
aforementioned transient, painless lid
swelling, often accompanied by mild
redness. In Stage 2, the atonic-ptosis
stage, the skin assumes a reddishbrown coloration, becoming telangiectatic and loose to the point of overhanging the lashes. Stage 3, termed
ptosis adipose, involves dehiscence of
the orbital septum with herniation of
orbital fat into the eyelid. Additional
complications of blepharochalasis may
include conjunctival hyperemia and
chemosis, entropion and ectropion.
Pathophysiology
The pathophysiology of dermatochalasis has not been well described.
Much of the process appears to
involve the normal involutional
changes of aging, including the
effects of gravity, loss of elastic tissue and degeneration of connective
tissue, which results in laxity, redundancy, and thinning of the epidermal
skin.8,9 Both mechanical (the repeated action of facial expression) and
photochemical (i.e. chronic exposure
to UV radiation) etiologies have been
8A REVI EW OF OPTOM E TRY
001_ro0612_hndbk.indd 8
proposed as causative factors.1,4,9 Less
commonly, systemic disorders—such
as Ehlers-Danlos syndrome, cutis
laxa, thyroid eye disease, renal failure
and amyloidosis—may hasten the
development of dermatochalasis.1,4
Some patients may additionally
have a genetic predisposition toward
developing dermatochalasis at a
younger age.10 One report suggested
that dermatochalasis may begin with
subclinical inflammation, accelerating
the elastolysis process and leading to
secondary lymphostasis (obstruction
and retention of lymphatic fluid).4
Blepharochalasis stems from
recurrent episodes of eyelid edema;
it is believed that the chronic exacerbating and remitting edema of
this condition results in a stretching
and subsequent atrophy of the eyelid tissue.4-6,11 Proposed etiologies
include both localized angioedema
and inflammatory mechanisms,
based upon histological studies and
biomarkers that have been identified
in patients with the disorder.4,12,13
Ultimately, damage to the levator
aponeurosis may ensue, resulting in
ptosis. Blepharochalasis is considered idiopathic in most instances,
though cases have been published
suggesting a systemic association
with conditions such as kidney
agenesis, vertebral abnormalities and
congenital heart defect.14
Management
Patients with asymptomatic dermatochalasis require little treatment.
Automated perimetry may be beneficial to document any significant
compromise to the visual field; any
such field defect may be an indication
for surgical intervention.2,3 Patients
should also be evaluated for blepharitis, trichiasis, ectropion, entropion or
dry eye and treated accordingly with
palliative and/or therapeutic agents,
epilation or surgical corrective procedures. If examination reveals any
other indications of underlying systemic disorders (e.g. thyroid or renal
disease), then appropriate laboratory
testing should be performed. Those
individuals with symptomatic dermatochalasis should be referred for
oculoplastic consultation.
Blepharoplasty is considered the
procedure of choice for dermatochalasis. Typically, this involves the
removal of a crescent-shaped wedge
of skin (and occasionally some of
the underlying muscle) from the
upper eyelid, with suturing of the
viable ends along the lid crease.15
The technique may be performed in
numerous ways incorporating a variety of instrumentation, from “cold
steel” (i.e. stainless steel scalpel) to
electrocautery to CO2 laser.16 More
extensive or severe cases may warrant
additional surgical measures, including browpexy (brow-lift surgery) and/
or lower eyelid blepharoplasty with
transconjunctival fat resection.1,17
Many clinicians consider the primary treatment of blepharochalasis
to be surgical. Medical therapy during the acute stages of the disease
remains controversial. The use of
systemic corticosteroids has been suggested, and while some have found
success with this treatment, others
have reported cases recalcitrant to
corticosteroid therapy.18-20 More
recently, reports of success using oral
diuretics and tetracycline derivatives
have been published.19-21 Because
the specific etiology of this disorder
JUNE 15, 2012
6/1/12 3:12 PM
Clinical Pearls
• Realize that dermatochalasis is
a normal, physiologic condition that
affects virtually all patients over the
age of 50 years, to varying degrees.
It is commonly asymptomatic and
requires little intervention. In contradistinction, blepharochalasis is an
atypical, pathologic syndrome that
can result in significant visual impairment of young, active adults.
• A common feature to both dermatochalasis and blepharochalasis is
the herniation of orbital fat through
the septum orbitale in the upper or
lower eyelids. This phenomenon is
referred to as steatoblepharon. Like
dermatochalasis, steatoblepharon is
common with age, and may be quite
pronounced in some individuals. It is
most often noted in the medial upper
eyelid. Treatment of this condition
involves transconjunctival blepharoplasty with resection of the excess
fatty tissue.
• Dermatochalasis should not be
confused with floppy eyelid syndrome, a condition in which the lids
become flaccid due to a loss of tarsal
elastin. Floppy eyelid syndrome
is most commonly seen in obese,
middle-aged men with respiratory
problems such as obstructive sleep
apnea. The poor lid-globe apposition in floppy eyelid syndrome often
results in symptomatic papillary conjunctivitis.
1. DeAngelis DD, Carter SR, Seiff SR.
Dermatochalasis. Int Ophthalmol Clin. 2002
Spring;42(2):89-101.
2. Fay A, Lee LC, Pasquale LR. Dermatochalasis
causing apparent bitemporal hemianopsia. Ophthal
Plast Reconstr Surg. 2003;19(2):151-3.
3. Ozdamar Y, Acaroglu G, Ustun H, et al. Visual-field
loss caused by excessive dermatochalasis due to
solar elastosis. Clin Exp Dermatol. 2009;34(7):e23940.
4. Koursh DM, Modjtahedi SP, Selva D, Leibovitch
I. The blepharochalasis syndrome. Surv Ophthalmol.
2009;54(2):235-44.
5. Huemer GM, Schoeller T, Wechselberger G,
et al. Unilateral blepharochalasis. Br J Plast Surg.
2003;56(3):293-5.
6. Dózsa A, Károlyi ZS, Degrell P. Bilateral
blepharochalasis. J Eur Acad Dermatol Venereol.
2005;19(6):725-8.
7. Brar BK, Puri N. Blepharochalasis—a rare entity.
Dermatol Online J. 2008 Jan 15;14(1):8.
8. Emesz M, Wohlfart C, Schaeppi H, et al.
Elastolysis of the eyelids. A rare cause of ptosis.
[Article in German] Ophthalmologe. 2004;101(5):50913.
9. Khavkin J, Ellis DA. Aging skin: histology, physiology, and pathology. Facial Plast Surg Clin North Am.
2011;19(2):229-34.
10. Kaneoya K, Momota Y, Hatamochi A, et al.
Elastin gene expression in blepharochalasis. J
Dermatol. 2005;32(1):26-9.
11. Jordan DR. Blepharochalasis syndrome: a
proposed pathophysiologic mechanism. Can J
Ophthalmol. 1992;27(1):10-5.
12. Grassegger A, Romani N, Fritsch P, et al.
Immunoglobulin A (IgA) deposits in lesional skin
of a patient with blepharochalasis. Br J Dermatol.
1996;135(5):791-5.
13. Jordan DR. Blepharochalasis syndrome: a
proposed pathophysiologic mechanism. Can J
Ophthalmol. 1992;27(1):10-5.
14. Ghose S, Kalra BR, Dayal Y. Blepharochalasis
with multiple system involvement. Br J Ophthalmol.
1984;68(8):529-32.
15. Har-Shai Y, Hirshowitz B. Extended upper
blepharoplasty for lateral hooding of the upper eyelid
using a scalpel-shaped excision: a 13-year experience. Plast Reconstr Surg. 2004;113(3):1028-35;
discussion 1036.
16. Biesman BS. Blepharoplasty: laser or cold steel?
Skin Therapy Lett. 2003 Nov-Dec;8(7):5-7.
17. Olver JM. Periocular dermatochalasis. Available
at: www.clinicalondon.co.uk/periocular-dermatochalasis. (accessed Dec 16, 2011).
18. Collin JR. Blepharochalasis. A review of 30 cases.
Ophthal Plast Reconstr Surg. 1991;7(3):153-7.
19. Lazaridou MN, Sandinha T, Kemp EG. Oral acetazolamide: A treatment option for blepharochalasis?
Clin Ophthalmol. 2007;1(3):331-3.
20. Drummond SR, Kemp EG. Successful medical
treatment of blepharochalasis: a case series. Orbit.
2009;28(5):313-6.
21. Karaconji T, Skippen B, Di Girolamo N, et al.
Doxycycline for treatment of blepharochalasis via
inhibition of matrix metalloproteinases. Ophthal Plast
Reconstr Surg. 2011 Sep 21. [Epub ahead of print].
HORDEOLUM
Signs and Symptoms
The prominent symptom of
patients presenting with hordeolum
EYELIDS AND ADNEXA
is still unclear, it is difficult to delineate a foolproof medical regimen for
all cases. The only certainty is that,
ultimately, surgery is necessary to
address the cosmesis of patients with
blepharochalasis. Blepharoplasty with
or without ptosis repair remains the
surgical technique of choice.4
Hordeola (upper lid) are typically acute and
painful.
is an acutely painful, focally swollen
eyelid exhibiting edema and erythema
directly adjacent to or surrounding
the affected eyelid margin gland or
cilia.1-8 Visual acuity is typically unaffected by the local infection so long
as the swelling of the region does
not obstruct the visual field, induce
distortion effects by compressing
the cornea or indirectly incite keratopathy.1-7 Associated inflammation
of the conjunctiva is possible, as is
mucopurulent discharge that may
ooze from the infected gland or from
the base of the affected cilia.2,3 The
affected area of the eyelid will exhibit
pain upon palpation and may hurt
upon blinking (often the first sign
the entity is evolving). Since the
condition results from infection of
the glands of the eyelid margin that
produce the oil element of the tears,
it can occur where the gland opens
(external) or within its inner workings (internal hordeolum). There will
be an associated lump within the eyelid in cases that are internal. There
may be an erythematous volcanic or
pimple-like lesion at the affected site
of the lid margin in external cases.1-7
Chronic eyelid disease and various
forms of blepharitis are frequently
present.1-10 While there has been no
reason to assign a sexual or racial predilection for patients with hordeola,
one recent study involving more than
5000 subjects found a prevalence for
blepharokeratoconjunctivitis in boys
over girls.2 Hordeola are among the
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most commonly acquired lid lesions
in children.6
Pathophysiology
The sebaceous glands of the eyelids (the meibomian glands, glands
of Moll and glands of Zeiss) are the
sites of origin for hordeola.1-10 There
are 20 to 30 glands in the upper lid
and 10 to 20 in the lower lid, that
are all embedded in the tarsal plate.
The glands of Zeiss are associated
with the eyelash follicles. All of these
glands produce the superficial lipid
layer of tears.6,10
Traditionally, a hordeolum represents bacterial infection of these
glands of the eyelid with subsequent abscess formation.1-10 If the
superficial glands of Zeiss or Moll
are involved, then the hordeolum
is considered to be external and
appears focal in nature.1-10 This will
be associated with a tender, inflamed
swelling at the lid margin, often
pointing anteriorly through the skin.
If the deeper meibomian glands are
involved or the infection becomes
prosperous inside the workings of the
gland preceding its opening, the hordeolum is considered to be internal.
Internal hordeola create more diffuse swelling of the tarsus and have a
greater propensity for creating cellulitis.1-10 In either case, the lesion may
enlarge and discharge either through
the conjunctiva or through the skin.110 Multiple recurrent hordeola associated with selective IgM deficiency
has been reported.7 Abnormal triglyceride fatty acid composition has
been discovered in association with
chronic blepharitis.9
The most commonly encountered organisms producing hordeola are Staphylococcus aureus and
Staphylococcus epidermis.2-6 Acute and
chronic inflammation associated with
hordeola may result in a hard retention known as a chalazion, especially
10A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 10
if it is untreated or improperly treated.
Spread of infection to neighboring
glands or other lid tissue anterior to
the tarsal plate may lead to the formation of preseptal cellulitis.1-6,10 While
uncommon, hordeola can produce
ocular surface disruptions as a thickened lid rubs against the cornea and
conjunctiva during blinking.8
Necrotizing fasciitis is a rare soft
tissue infection with the ability
to rapidly spread. It is characterized by widespread necrosis of the
superficial fascia.12 While it usually occurs about the limbs and the
abdomen, one case of periocular
necrotizing fasciitis originating from
a hordeolum has been reported in a
patient who was immunocompromised.11 The infection occurs secondary to Group A beta-hemolytic
Streptococcus and Staphylococcus
aureus.11 The eyelid has an excellent
blood supply, making it an ideal
place for supporting this type of
growth.11
Management
Hordeola are generally self limiting and will resolve within five to
seven days with spontaneous drainage of the abscess.1-11 Traditionally,
the hallmark treatment for hordeola
is the use of topical antibiotic solutions and/or ointments coupled
with warm/hot compresses.1-11
Unfortunately, unless the lesion is
superficial, this treatment yields
poor results, as topical antibiotics
may not generate sufficient intratissue concentrations to be therapeutic.3 Topical antibiotics (solution or
ointment) are prudent when there is
significant concomitant blepharitis
or acne rosacea.1-11 The advantage
of ointments is that they provide
increased contact time with the
infection. The disadvantage of ointments is cosmesis (appearing greasy)
with the potential to blur vision.
Oral antibiotic therapy is necessary
when hordeola do not resolve with a
conservative topical approach.10,12 If
the hordeolum is external and there
is a pimple formed, the lesion can be
perforated and drained (anesthetic is
usually unnecessary) or nearby lashes
can be epilated to enhance drainage. Digital expression of purulent
material in the office will expedite
healing, but is not absolutely necessary. Oral antibiotic therapy includes
cephalexin 500mg p.o. b.i.d., dicloxacillin 250mg p.o. q6h; erythromycin
or tetracycline 250mg p.o. q.i.d.; or
amoxicillin 500mg p.o. t.i.d. for 10
days. Warm/hot compresses, applied
directly to the lesion, should be
maintained to enhance pointing and
drainage. Reassessment can generally
be scheduled weekly until resolution.
Early recognition of failed therapy
should prompt reevaluation of both the
diagnosis and the etiology.10-12 Surgical
debridement and intensive intravenous
antibiotic treatment are necessary for
any non-resolving cellulitic expansion
or any tissue destructive (necrotizing
fasciitis) complications.11
Clinical Pearls
• The most common misdiagnosis
of a hordeolum is a chalazion. The
distinguishing factor is pain on palpation. If the lesion is not painful
upon palpation, then it is most likely
a chalazion.
• Topical treatment of infectious
lid conditions offer a conservative
approach. Results will be variable as
this mode presents some therapeutic
obstacles.
• Occult HIV disease should be
entertained in a young person with
an atypical hordeolum as Kaposi’s
sarcoma can mimic this condition.13
• Recurrent lesions or lesions
associated with madarosis should
undergo biopsy to rule out sebaceous
cell carcinoma.14-16
JUNE 15, 2012
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PHTHIRIASIS PALPEBRARUM
Signs and Symptoms
Adult patients that manifest this
particular form of blepharoconjunctivitis typically are sexually active.1
There is often concurrent genital
involvement.2 The patient will frequently report eyelid irritation and
itching; pruritic lid margins will be
grossly apparent. Biomicroscopically,
there will be visible organisms and
egg sacs (nits), which may be rup-
EYELIDS AND ADNEXA
1. Panicharoen C, Hirunwiwatkul P. Current pattern treatment of hordeolum by ophthalmologists in
Thailand. J Med Assoc Thai. 2011;94(6):721-4.
2. Gupta N, Dhawan A, Beri S, D’souza P. Clinical
spectrum of pediatric blepharokeratoconjunctivitis. J
AAPOS. 2010;14(6):527-9.
3. Lindsley K, Nichols JJ, Dickersin K. Interventions
for acute internal hordeolum. Cochrane Database
Syst Rev. 2010 8(9):CD007742.
4. Ramesh S, Ramakrishnan R, Bharathi MJ, et al.
Prevalence of bacterial pathogens causing ocular
infections in South India. Indian J Pathol Microbiol.
2010;53(2):281-6.
5. Bamford JT, Gessert CE, Renier CM, et al.
Childhood stye and adult rosacea. J Am Acad
Dermatol. 2006;55(6):951-5.
6. Lederman C, Miller M. Hordeola and chalazia.
Pediatr Rev. 1999;20(8):283-4.
7. Kiratli HK, Akar Y. Multiple recurrent hordeola
associated with selective IgM deficiency. J AAPOS.
2001;5(1):60-1.
8. Shine WE, McCulley JP. Meibomian gland triglyceride fatty acid differences in chronic blepharitis
patients. Cornea. 1996;15(4):340-6.
9. Maldonado MJ, Juberias JR, Moreno-Montanes
J. Extensive corneal epithelial defect associated with internal hordeolum after uneventful laser
in situ keratomileusis. J Cataract Refract Surg.
2002;28(9):1700-2.
10. Neff AG, Carter CD. Benign eyelid lesions.
In: Yanoff M, Duker JS. Ophtalmology 2nd ed.
Philadelphia, PA: Mosby;2004: 698-710.
11. Lim VS, Amrith S. Necrotising fasciitis of the eyelid with toxic shock due to Pseudomonas aeruginosa.
Singapore Med J. 2010;51(3):e51-3.
12. Miller J. Acinetobacter as a causative agent in
preseptal cellulitis. Optometry. 2005;76(3):176-80.
13. Brun SC, Jakobiec FA. Kaposi’s sarcoma of the
ocular adnexa. Int Ophthalmol Clin. 1997;37(4):25-38.
14. Iglesias I, Troyano J, Díaz-Valle D, et al.
Sebaceous carcinoma. Study of two cases. Arch Soc
Esp Oftalmol. 2008;83(7):445-8.
15. Keskinaslan I, Pedroli GL, Piffaretti JM,
et al. Eyelid sebaceous gland carcinoma in a
young Caucasian man. Klin Monbl Augenheilkd.
2008;225(5):422-3.
16. Kodama T, Tane N, Ohira A, et al. Sclerosing
sweat duct carcinoma of the eyelid. Jpn J
Ophthalmol. 2004;48(1):7-11.
Phthiriasis organism.
Phthiriasis infestation of the eyelids.
tured or intact, within the scalp,
hair, eyebrows, eyelashes or beard;
visible blue skin lesions (louse
bites); reddish brown deposits (louse
feces); secondary blepharitis with
preauricular adenopathy; follicular
conjunctivitis; and, in severe cases,
marginal keratitis.3-6 Superinfection
of bites may lead to preauricular
gland swelling.
grasp (eyelashes, beard, chest, axillary region, pubic region).5,7 Both
organisms suck the blood of the
host, and Pediculus humanus may
serve as a vector of diseases, such as
typhus and trench fever.
Pediculus and Phthirus interbreed freely. Both types of lice lay
eggs on the hair shafts. These eggs
remain firmly adherent, resisting both mechanical and chemical removal.5,9 Pediculus possesses
good mobility and can pass from
person to person by either close
contact with an infested individual
or by contact with contaminated
bedding. Conversely, Phthirus are
slow-moving organisms that cannot
typically pass unless cilia are brought
into close proximity with infested
cilia, though contaminated bedding
is a possible source.10,11 Both species
are associated with crowding or poor
personal hygiene.
Pathophysiology
Pediculosis refers to eyelid infestation by Pediculus humanus corporis
(body louse) or capitis (head louse).
These organisms rarely will infect
the eyelids, though. Phthiriasis
palpebrarum refers to eyelid infestation by Phthirus pubis (pubic louse,
sometimes referred to as crab louse).
Eyelid infestation is almost always
by Phthirus pubis. However, this
organism will occasionally infect the
scalp.7 It appears that outbreaks of
Pediculus capitis are more frequent
in the warmer months, whereas
Phthirus pubis are more dominant in
the cooler months.8
Pediculus is an organism 2mm to
4mm long that typically infests the
hair of the patient. Infestation of the
cilia is rare and only occurs in the
worst cases. Phthirus is 2mm long
with a broad-shaped, crab-like body.
Its thick, clawed legs make it less
mobile than the Pediculus species
and lend it to infesting areas where
the adjacent hairs are within its
Management
Management begins with forceps
removal of all visible organisms
and nits.2,3,5,6,9,12 The removed
organisms and nits should be killed
by placing them onto an alcohol
wipe (or dipped in alcohol). They
can then be discarded. Adjunctive
topical therapy may be employed to
ensure eradication following physical
removal. If physical removal is not
possible or practical, topical therapy
will suffice. The lice and nits can
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be smothered with petroleum jelly
or other bland ophthalmic antibiotic ointments t.i.d. for one to two
weeks. Even pilocarpine gel has
been used successfully. The organisms breathe through their body
walls, thus ointments are effective
as a tool to smother them. Other
topical therapies that act to interfere with their respiratory systems
include 1% yellow mercuric oxide,
20% fluorescein (as used in angiography), 2.5% permethrin cream
or 3% ammoniated mercuric oxide
b.i.d. for one to two weeks.4,6,13,14
Alternate treatments include cholinesterase inhibitors such as physostigmine.6,15-17 Typically, the nits will
survive a single application of these
agents as the egg is totally encased
by a proteinaceous sheath, and must
hatch before becoming susceptible
to topical therapy.18 For this reason,
therapy is always recommended for
one to three weeks.
Oral Stromectol (ivermectin,
Merck & Co., Inc.), an agent for
the treatment of scabies infection as
well as onchocerciasis, has had some
anecdotal success in the management of phthiriasis palpebrarum.19
When phthiriasis palpebrarum is
diagnosed, genital involvement must
be suspected. Infested patients should
be instructed to obtain and use a
pediculocidal medicated shampoo.
These include, but are not limited
to, lindane 1%; permethrin 1% (marketed as Nix cream rinse by Warner
Lambert; Elimite cream by Allergan;
or Acticin cream by Mylan Bertek);
A-200 Pyrinate (pyrethrins, piperonyl butoxide and kerosene, Hogil
Pharmaceutical Corp.); and Kwell
(lindane, Reed and Carnrick), or RID
(pyrethins/piperonyl butoxide, Bayer
Healthcare LLC), which are safe,
effective, non-prescription pediculicides. However, due to toxicity, these
agents cannot be used on the eyelids.
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001_ro0612_hndbk.indd 12
Patients must be instructed to thoroughly wash all clothing and linens
that may have been exposed. Clothing,
linen and personal items must all be
disinfected with heat of 50° C (125° F)
for 30 minutes or more.
Medical testing for other sexually
transmitted diseases, including HIV
infection, should be recommended.1
When the issue is discovered in children, contraction within the school
network and abuse must be considered.10 Such infestations should be
reported to the child’s pediatrician.
Clinical Pearls
• Follow-up is required through
seven to 10 days, as nits hatch within that period.
• Educate patients about how
the organisms are transmitted, and
advise that they should refrain from
all close and personal/sexual contact
with others until the disease is 100%
resolved. Finally, counsel patients to
educate exposed partners to report
for examination and evaluation.
• Mechanical removal at the biomicroscope with a jeweler’s forceps
is time consuming, but it is the
preferred method of treatment. This
can be a detailed, painstaking process. In that the egg sacs are termed
“nits,” the lay public has historically
referred to this overall infestation as
“nits.” This is where the terms, “nitpicker” and “nitpicking” come from.
• Live organisms will cling tightly
to the eyelashes and many lashes
will be removed during this process.
Educate the patient to expect some
discomfort associated with inadvertent lash removal.
• Smearing the lids and lashes
with an ophthalmic ointment may
make removal easier as the organisms
cannot grasp as firmly to the greasy
lashes. However, this may make visualizing and grasping the organisms
with forceps more difficult.
• There is virtually no chance of the
doctor or other office staff members
contracting the infestation through the
examination or removal process.
1. Beltrami C, Manfredi R, D’Antuono A, et al.
Sexually-transmitted infections in adolescents
and young adults in a large city of Northern Italy:
a nine-year prospective survey. New Microbiol.
2003;26(3):233-41.
2. Lopex Garcia JS, Garcia Lozano I, Martinez
Garchitorena J. Phthiriasis palpebrarum: diagnosis and treatment. Arch Soc Esp Oftalmol.
2003;78(7):365-74.
3. Ikeda N, Nomoto H, Hayasaka S, et al. Phthirus
pubis infestation of the eyelashes and scalp hairs in
a girl. Pediatr Dermatol. 2003;20(4):356-7.
4. Morsy TA, El-Ghazali SM. A four years old girl
with phthiriasis pubis infestation. J Egypt Soc
Parasitol. 1999;29(3):893-6.
5. Lin YC, Kao SC, Kau HC, et al. Phthiriasis
palpebrarum: an unusual blepharoconjunctivitis.
Zhonghua Yi Xue Za Zhi (Taipei). 2002;65(10):498500.
6. Couch JM, Green WR, Hirst LW, et al.
Diagnosing and treating Phthirus pubis palpebrarum. Surv Ophthalmol. 1982;26(4):219-25.
7. Hernandez Contreras N, Isla Garcia M, Vega
Correa E. Hair infestation by Phthirus pubis
(Anoplura: Pediculidae). Rev Cubana Med Trop.
2001;53(1):63-5.
8. Mimouni D, Ankol OE, Gdalevich M, et al.
Seasonality trends of Pediculosis capitis and
Phthirus pubis in a young adult population: followup of 20 years. J Eur Acad Dermatol Venereol.
2002;16(3):257-9.
9. Schenone H. Eyelid infestation by Phthirus pubis
in a boy. Bol Chil Parasitol. 2000;55(1-2):25-6.
10. Charfi F, Ben Zina Z, Maazoun M, et al.
Phthiriasis pubis palpebrarum in children. Diagnosis
and treatment. J Fr Ophtalmol. 2005;28(7):765-8.
11. Niazi MK, Arain MA. Phthiriasis palpebrarum. J
Coll Physicians Surg Pak. 2009;19(9):589-90.
12. Yoon KC, Park HY, Seo MS, et al. Mechanical
treatment of phthiriasis palpebrarum. Korean J
Ophthalmol. 2003;17(1):71-3.
13. Ashkenazi I, Desatnik HR, Abraham FA. Yellow
mercuric oxide: a treatment of choice for phthiriasis
palpebrarum. Br J Ophthalmol. 1991;75(6):356-8.
14. Mathew M, D’Souza P, Mehta DK. A new treatment of pthiriasis palpebrarum. Ann Ophthalmol.
1982;14(5):439-41.
15. Kumar N, Dong B, Jenkins C. Pubic lice effectively treated with Pilogel. Eye. 2003;17(4):538-9.
16. Pinckney J 2nd, Cole P, Vadapalli SP, Rosen
T. Phthiriasis palpebrarum: a common culprit
with uncommon presentation. Dermatol Online J.
2008;14(4):7.
17. Turgut B, Kurt J, Catak O, Demir T. Phthriasis
palpebrarum mimicking lid eczema and blepharitis.
J Ophthalmol. 2009;2009:803951. Epub 2009 Nov
30.
18. Burkhart CN, Gunning W, Burkhart CG.
Scanning electron microscopic examination of the
egg of the pubic louse (Anoplura: Pthirus pubis). Int
J Dermatol. 2000;39(3):201-2.
19. Burkhart CN, Burkhart CG. Oral ivermectin
therapy for phthiriasis palpebrum. Arch Ophthalmol.
2000;118(1):134-5.
JUNE 15, 2012
6/1/12 3:12 PM
CONJUNCTIVA & SCLERA
Signs and Symptoms
Episcleritis is an inflammatory condition of the external eye involving the
conjunctiva and its underlying connective tissue.1-11 The signature presentation demonstrates a sectorial injection
involving both the episcleral tissues and
overlying conjunctiva, usually concentrated in either the nasal or temporal
quadrant without discharge.1-10 It is
hard to document epidemiologic data as
the inflammation is primarily a response
to either a noxious/toxic exposure (solid,
liquid, gas) or secondary to an underlying systemic disease.1-7 Idiopathic cases
have been documented and seem to
account for 33% of occurrences.12,13
Acute onset is typical, with patients
often reporting that they “woke up with
a red eye.”7 Superior injection has the
potential to go unnoticed and may be
completely masked by the upper eye lid
in primary gaze. Most cases of episcleritis are unilateral; however, it may occur
bilaterally in cases of exposure or cases
precipitated by underlying systemic
disease.7 Occasionally, a translucent
white nodule is seen within the inflamed
area (nodular episcleritis).7,11 Nodular
episcleritis represents focal concentration
of the inflammatory response.7,11 The
nodule is often linked to underlying tissues and can be distinguished from cysts
and phlyctenular lesions by its characteristic lack of mobility with the conjunctiva.7,11 Patients may complain of mild
pain or tenderness to the affected region,
pain upon manipulation or a stabbing
sensation upon moving the eyes (particularly saccadic movement). Visual acuity is unaffected.1-12 The cornea is also
unaffected, although long-standing or
recurrent episcleritis may lead to dellen
formation.8 While it is rare that episcleritis provokes anterior iritis/uveitis, like
all ocular inflammatory reactions, it is
possible anterior chamber cells may be
seen in more pronounced cases.1-12
Diagnostically, most cases of episcleritis will blanch with the application of
topical 2.5% phenylephrine.11 In contrast, more significant ocular inflammations such as scleritis and uveitis will not
result in blanching. Gently manipulating
the inflamed region with a cotton-tipped
applicator may also help distinguish the
level of inflammation.
Pathophysiology
Episcleritis represents an inflammation of the episclera, the highly
vascularized ocular tunic that encircles
the globe between the overlying conjunctiva and the underlying sclera.1,7-12
The inflammatory response in these
cases remains localized to the superficial episcleral vascular network with
the histopathology showing nongranulomatous inflammation and vascular
dilatation with perivascular infiltration.14 The disorder may be idiopathic
or in association with some underlying systemic disease.1-12,15,16 Among
those conditions linked to chronic or
recurrent episcleritis are: rheumatoid
arthritis, polyarteritis nodosa, systemic
lupus erythematosus, inflammatory
bowel disease, sarcoidosis, Wegener’s
granulomatosis, tuberculosis, Lyme
disease, gout, herpes zoster and syphilis.4,6,7,10,11,15,16 The nodular form comprises the minority of cases.14
Management
Most cases of episcleritis are selflimiting, resolving spontaneously within
two to three weeks even in the absence
of treatment.7,11,12 Patients who are
symptomatic or who do not like their
Nodular episcleritis.
cosmetic appearance may benefit from a
regimen of cold compresses, lubricants,
topical nonsteroidal anti-inflammatory
preparations and topical corticosteroids.1-12 Since the inflammation produced in episcleritis is relatively superficial, virtually all topical steroids are
acceptable, including fluorometholone,
rimexolone, loteprednol, prednisolone
and difluprednate. Dosing on both the
topical NSAID and topical steroid typically range from b.i.d. to q4h.1,7,11,12
Cycloplegia is rarely necessary.
Recalcitrant or severe cases associated
with systemic disease may require oral
nonsteroidal anti-inflammatory drugs.
Viable options for these rare instances
include ibuprofen (600mg to 800mg
b.i.d. to q.i.d.), naproxen sodium
(250mg to 500mg t.i.d.), or indomethacin (25mg to 75mg b.i.d.).1,7,11,12
The follow up on these cases should
be weekly. Patients placed on steroids of
any kind are at risk for steroid-induced
elevation of IOP.17 Difluprednate also
possesses a similar risk profile for this
event.18 However, the addition of topical
aqueous suppressants along with some
modulation of the topical steroidal
agent almost always mitigates the pressure spike. Because of the association
with systemic disorders, patients with
extremely severe presentations or recurrences should be referred for a medical
evaluation.4,6,7,10,11,15,16
Clinical Pearls
• Episcleritis is a condition similar to
subconjunctival hemorrhage: it typically
looks worse than it is and, in most cases,
it is self-limiting.
• Care must be taken to distinguish
episcleritis from the more severe scleritis, which has more serious implications for visual compromise and ocular
sequelae. Scleritis is typically more
painful, more commonly encountered
bilaterally and much more likely to
demonstrate an attendant uveitis. Unlike
episcleritis, 2.5% phenylephrine will not
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 13
CONJUNCTIVA & SCLERA
EPISCLERITIS
13A
6/1/12 3:12 PM
induce blanching of the vascular injection in cases of true scleritis.
• Not every case of sectorial injection is episcleritis. Trichiasis may
mechanically induce a “pseudo-episcleritis.” Signs and symptoms should
be considered before prescribing any
medications.
1. Kirkwood BJ, Kirkwood RA. Episcleritis and scleritis.
Insight. 2010;35(4):5-8.
2. Akpek EK, Uy HS, Christen W, Gurdal C, et al.
Severity of episcleritis and systemic disease association. Ophthalmology. 1999;106(4):729-31.
3. Rajoo SG, Gandhewar J. Recurrent episcleritis
in relation to menstruation: a case report. Cornea.
2011;30(9):1035-6.
4. Chatziralli IP, Kanonidou E, Chatzirallis A, et al.
Episcleritis related to drug-induced lupus erythematosus following infliximab therapy: a case report. Case
Report Med. 2011;2011:696285.
5. Sohn EH, Wang R, Read R, et al. Long-term,
multicenter evaluation of subconjunctival injection of
triamcinolone for non-necrotizing, noninfectious anterior
scleritis. Ophthalmology. 2011;118(10):1932-7.
6. Yoo JH, Chodosh J, Dana R. Relapsing polychondritis: systemic and ocular manifestations, differential diagnosis, management, and prognosis. Semin Ophthalmol.
2011;26(4-5):261-9.
7. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis
and scleritis: Clinical features and treatment results. Am
J Ophthalmol.2000;130(4):469-76.
8. Casser L, Lingel NJ. Diseases of the cornea.
In: Bartlett JD, Jaanus SD, eds. Clinical Ocular
Pharmacology, 3rd ed. Boston: ButterworthHeinemann;1995:679-745.
9. Sainz de la Maza M, Jabbur NS, Foster CS.
Severity of scleritis and episcleritis. Ophthalmology
1994;101(2):389-96.
10. Pavesio CE, Meier FM. Systemic disorders
associated with episcleritis and scleritis. Curr Opin
Ophthalmol. 2001;12(6):471-8.
11. Goldstein DA, Tessler HH. Episcleritis, scleritis
and other scleral disorders. In: Yanoff M, Duker JS.
Ophtalmology. 2nd ed. Philadelphia: Mosby;2004:
511-9.
12. Williams CP, Browning AC, Sleep TJ, et al. A randomised, double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis. Eye (Lond).
2005;19(7):739-42.
13. Watson PG, Hayreh SS. Scleritis and episcleritis. Br
J Ophthalmol.1976;60(3):163-91.
14. Kalantan H, Al-Shawan S, Al-Katan H, et al.
Nodular episcleritis in a young patient. Saudi J
Ophthalmol. 2006;20(3):191-193.
15. Sadiq SA, Jennings CR, Jones NS, Downes RN.
Wegener’s granulomatosis: The ocular manifestations
revisited. Orbit. 2000;19(4):253-261.
16. Tarabishy AB, Schulte M, Papaliodis GN, Hoffman
GS. Wegener’s granulomatosis: clinical manifestations,
differential diagnosis, and management of ocular and
systemic disease. Surv Ophthalmol. 2010;55(5):429-44.
17. Razeghinejad MR, Katz LJ. Steroid-induced iatrogenic glaucoma. Ophthalmic Res. 2011;47(2):66-80.
18. Meehan K, Vollmer L, Sowka J. Intraocular pressure
elevation from topical difluprednate use. Optometry.
2010;81(12):658-62.
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001_ro0612_hndbk.indd 14
SCLERITIS
Signs and Symptoms
Scleritis represents an inflammation of the sclera of the eye.1-11 As the
sclera holds a proximity to the choroid
and its abundant innervation, scleritis
almost always produces symptoms.1-10
Patients characteristically report a
severe, boring ocular pain that may
radiate to involve the adjacent head and
facial regions. Photophobia and lacrimation are common. Decreased vision
is possible depending upon the involvement of the cornea, the amount of
inflammation and the quadrants of the
eye that are involved.6-9 While the disease may be local and idiopathic, many
instances of scleritis evolve secondary
to advancing systemic disease (typically
an immune-mediated inflammatory
disease such as arthritis or Wegener’s
granulomatosis), the side effects of
medicine or as a complication of ocular
surgery.6-8,12-17 This makes the epidemiology difficult to calculate.6-8,12-17 In
one recent study, a slight preponderance was found for women over men.16
Examination typically reveals significant dilation of the scleral vessels, as
well as the overlying vasculature of the
episclera and bulbar conjunctiva.4-6,17
The affected eye may assume a deep
red, almost purple hue (violaceous).4-6
The presentation may be sectorial or
diffuse.4,5 The condition is bilateral
in more than 50% of cases, although
it is often asymmetric.6 A concurrent
anterior chamber reaction is noted in
upwards of 40% of patients with scleritis.10,11 Corneal involvement is also
possible, and may present as an infiltrative stromal keratitis, non-inflammatory
corneal thinning or peripheral ulcerative
keratitis.3,10,18 Glaucoma in the form of
an angle closure secondary to choroidal
effusion and expansion is possible.19
Severe cases may present with overlying interpalpebral inflammatory nodules,
which develop in the limbal region.4-6,10
In necrotizing scleritis, the sclera may
become transparent due to chronic
inflammation, revealing the underlying
dark blue hue of the choroid.4-6,20 The
most destructive form of necrotizing
scleritis is scleromalacia perforans.5,6,21 It
presents insidiously without substantial
pain or visible inflammatory signs.5,6,21
Uveal herniation through the thinned or
perforated scleral wall is a classic manifestation that may result in the catastrophic outcome of enucleation.5,6,21,22
Finally, scleritis may also affect more
posterior structures of the eye, including the choroid and retina.1,4-6,16,19,23-25
When posterior involvement occurs
along with anterior scleritis the diagnosis is straightforward. However, a purely posterior scleritis is uncommon and
may be quite variable.5,9,16 Posterior
scleritis presents with pain and loss of
vision.5,9,16,23-25 It less commonly presents with diplopia and/or proptosis.23,24
Dilated fundus examination may reveal
a focal choroidal mass or effusion, choroidal folds, optic disc edema, retinal
folds, cystoid macular edema or exudative macular detachment.23-25 Ocular
ultrasonography (B-scan) demonstrates
increased thickness of the ocular coats
and/or fluid in the episcleral space posteriorly and may be essential to make
the diagnosis.23
Pathophysiology
Scleritis represents a primary inflammation of the sclera.1-17 Although the
pathogenesis is not entirely understood,
research points to a deposition of
immune complexes within the sclera,
leading to a vasculitis with associated inflammatory cell infiltration and
edema.26 Pathogenic mechanisms point
to enzymatic degradation of collagen
fibrils by resident cells and infiltrating
leukocytes.17 Several forms of inflammation have been distinguished histologically. Interestingly, although the disease
typically presents with engorgement of
scleral vessels, vasculitis is not universally
JUNE 15, 2012
6/1/12 3:12 PM
Management
Topical therapy for scleritis is
designed to ameliorate the symptoms
associated with the anterior segment
inflammation.1,4-7,17,19 The primary
focus should be the identification and
treatment of the underlying cause.1,2,46,14,15,17,29,31-34 Topical medications are
not sufficient to appropriately manage
these conditions. Cycloplegia (scopolamine 0.25%, homatropine 5%, atropine
1%, q.d to t.i.d.) and topical steroid
therapy (prednisolone acetate 1% q2h to
q.i.d., difluprednate q4h to q.i.d.) should
be combined with appropriate medications to address the severity of the
condition as well as the underlying cause
(i.e., infectious, autoimmune). Systemic
anti-inflammatory agents are also req
uired.1,2,4-6,14,15,17,29,31-34 With respect
to resolving the ocular inflammation,
oral non-steroidal anti-inflammatory
drugs (NSAIDs) are generally used as
first-line treatment for mild to moderate, non-necrotizing, anterior scleritis.
Recommended regimens may include
ibuprofen (600mg to 800mg q.i.d.),
naproxen sodium (250mg to 500mg
t.i.d.) or indomethacin (25mg to 75mg
q.d. to t.i.d.).1,2,4-6,14,15,17 If the inflammation is more severe or necrotizing,
or if NSAIDs alone fail to suppress the
inflammation, systemic corticosteroids
are indicated.1,2,4-6,14,15,17 Oral prednisone 60mg to 80mg p.o. q.d. should
be given for two to three days and then
slowly tapered to 10mg to 20mg daily.
A small maintenance dose may be
required to control the condition.4-6,17
Systemic immunosuppressive agents
such as cyclophosphamide, cyclosporine
or methotrexate are necessary in the
most severe cases.4-6,35,36 Rituximab is
a monoclonal antibody that has been
used in the treatment of lymphoma,
leukemias, transplant rejection and some
autoimmune disorders.37,38 Rituximab
has been documented as an alternative treatment in severe scleritis that is
refractive to conventional therapy.37,38
Given the potential for adverse reactions
as well as interactions that may provoke
or worsen other systemic conditions, all
of these oral or intravenous medicines
should be initiated and monitored by
the patient’s internist or rheumatologist.
Scleritis management may range from
several weeks to more than a year.
Scleromalacia perforans tends to be
poorly responsive to all forms of therapy.
Globe perforation can result.5,6,21,22 The
vast majority of these patients suffer
from severe autoimmune disease and the
five-year survival rate for these individuals is poor.5,6,10,21
Clinical Pearls
• Since the onset of scleritis is often
slow and insidious, patients in the early
stages may be only mildly symptomatic
and the condition initially misdiagnosed.
• The differential diagnosis between
episcleritis and scleritis may be difficult.
Unlike episcleritis, scleritis does not
show significant blanching with topical
phenylephrine, nor can the vessels be
manipulated with a cotton-tipped applicator. Some sources suggest that viewing
the eye under regular sunlight helps to
reveal its true violaceous color, aiding in
the diagnosis.
• Unlike episcleritis, scleritis presents a significant risk of vision loss due
to “collateral damage.” The choroid,
cornea, retina and even optic nerve are
subject to damaging inflammation.
Additionally, scleral thinning poses the
risk of globe rupture.
• In all cases of scleritis, one should
assume the etiology to be underlying
systemic disease until proven otherwise.
Patients should be referred for a comprehensive medical evaluation, including
serology and radiology. Specific tests
may include: complete blood count
(CBC) with differential and platelets,
antinuclear antibody (ANA), human
leukocyte antigen (HLA) testing,
rheumatoid factor (RF), angiotensinconverting enzyme (ACE), rapid plasma
reagin (RPR), Lyme titer, chest X-ray,
and sacroiliac joint films. A rheumatologist is likely the best referral source.
• Patients placed on steroids of any
kind (topical, oral or inhaled) are at risk
for steroid-induced elevation of IOP.
Difluprednate also possesses a similar
risk profile for this event.39 However,
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 15
CONJUNCTIVA & SCLERA
present at the microscopic level.17 One
recent report described a T-helper cell
population known as Th-17, and implicated its association with the inflammatory process and scleritis formation.1
Once the inflammatory cascade
begins, destruction of the scleral collagen
matrix can ensue if prompt intervention
is not initiated.27,28 Chronic inflammation of the sclera may instigate capillary
closure and subsequent necrosis of focal
or diffuse areas of tissue.11 Capillary closure may be observed under a slit lamp
as unusual white patches of tissue. Severe
anterior chamber inflammation may lead
to subsequent cataract formation, trabecular meshwork outflow stasis, synechial
angle closure and secondary glaucoma.11
Scleritis can be associated with both
infectious and non-infectious vectors.
Infectious scleritis can be very difficult to diagnose as it may mimic an
immune-mediated disease.12 Although
uncommon, infectious scleritis can occur
following subconjunctival corticosteroid
injections.12
While the etiology remains idiopathic for many cases of scleritis, more
than half are associated with systemic
disease.4,6-8,10,12,17,29 Posterior and
necrotizing forms of scleritis have an
even higher incidence of underlying disease.29,30 More than 50 distinct disease
entities have been associated with scleritis in the literature. The most common
related disorders are rheumatoid arthritis, polyarteritis nodosa, systemic lupus
erythematosus, inflammatory bowel
disease, sarcoidosis, Wegener’s granulomatosis, tuberculosis, herpes zoster and
syphilis.1,2,4-6,14,15,17,29,31-34
15A
6/4/12 2:30 PM
Scleritis in a patient with rheumatoid arthritis.
the addition of topical aqueous suppressants along with some modulation of
the topical steroidal agent almost always
mitigates the pressure spike.
1. Rachitskaya A, Mandelcorn ED, Albini TA. An update
on the cause and treatment of scleritis. Curr Opin
Ophthalmol. 2010;21(6):463-7.
2. Moreland LW, Curtis JR. Systemic nonarticular manifestations of rheumatoid arthritis: focus on inflammatory
mechanisms. Semin Arthritis Rheum. 2009;39(2):132-43.
3. Galor A, Thorne JE. Scleritis and peripheral ulcerative
keratitis. Rheum Dis Clin North Am. 2007;33(4):835-54.
4. Kirkwood BJ, Kirkwood RA. Episcleritis and scleritis.
Insight. 2010;35(4):5-8.
5. Goldstein DA, Tessler HH. Episcleritis, scleritis and other
scleral disorders. In: Yanoff M, Duker JS. Ophtalmology
2nd ed. Philadelphia: Mosby;2004:511-9.
6. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis
and scleritis: Clinical features and treatment results. Am J
Ophthalmol. 2000;130(4):469-76.
7. McMullen M, Kovarik G, Hodge WG. Use of topical steroid therapy in the management of nonnecrotizing anterior
scleritis. Can J Ophthalmol. 1999;34(4):217-21.
8. Tuft SJ, Watson PG. Progression of scleral disease.
Ophthalmology. 1991;98(4):467-71.
9. Saikia P, Nashed A, Helbig H, Hillenkamp J. Bilateral
posterior scleritis: an idiopathic painless presentation. Ocul
Immunol Inflamm. 2010;18(6):452-3.
10. Castells DD. Anterior scleritis: Three case reports and
a review of the literature. Optometry. 2004;75(7):430-44.
11. Sainz de la Maza M, Foster CS, Jabbur NS. Scleritisassociated uveitis. Ophthalmology. 1997;104(1):58-63.
12. Gharaee H, Khalife M, Poor SS, Abrishami M.
Infectious scleritis after subtenon triamcinolone acetonide
injection. Ocul Immunol Inflamm. 2011;19(4):284-5.
13. Ahn SJ, Oh JY, Kim MK, et al. Clinical features,
predisposing factors, and treatment outcomes of scleritis in the Korean population. Korean J Ophthalmol.
2010;24(6):331-5.
14. Mehta M, Dacey M, Stephen Foster C. Recurrent conjunctivitis and scleritis secondary to coexistent conjunctival
pemiphigus vulgaris and cryptic herpes simplex infection:
a case report. Ocul Immunol Inflamm. 2010;18(6):454-6.
15. Zlatanović G, Veselinović D, Cekić S, et al. Ocular
manifestation of rheumatoid arthritis-different forms and
frequency. Bosn J Basic Med Sci. 2010;10(4):323-7.
16. Keino H, Watanabe T, Taki W, et al. Clinical features
and visual outcomes of Japanese patients with scleritis. Br
J Ophthalmol. 2010;94(11):1459-63.
17. Smith JR, Mackensen F, Rosenbaum JT. Therapy
insight: scleritis and its relationship to systemic autoimmune disease. Nat Clin Pract Rheumatol. 2007;3(4):219-
16A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 16
26.
18. Sainz de la Maza M, Foster CS, Jabbur NS, Baltatzis
S. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. Arch Ophthalmol.
2002;120(1):15-9.
19. Ikeda N, Ikeda T, Nomura C, Mimura O. Ciliochoroidal
effusion syndrome associated with posterior scleritis. Jpn
J Ophthalmol. 2007;51(1):49-52.
20. Moreno Honrado M, del Campo Z, Buil JA. A case of
necrotizing scleritis resulting from Pseudomonas aeruginosa. Cornea. 2009;28(9):1065-6.
21. Wu CC, Yu HC, Yen JH, et al. Rare extra-articular
manifestation of rheumatoid arthritis: scleromalacia perforans. Kaohsiung J Med Sci. 2005;21(5):233-5.
22. Herrera-Esparza R, Avalos-Díaz E. Infliximab treatment in a case of rheumatoid scleromalacia perforans.
Reumatismo. 2009;61(3):212-5.
23. McCluskey PJ, Watson PG, Lightman S, et al,
Posterior scleritis. Clinical features, systemic associations,
and outcome in a large series of patients. Ophthalmology.
1999;106(12):2380-6.
24. Krist D, Wenkel H. Posterior scleritis associated with Borrelia burgdorferi (Lyme disease) infection.
Ophthalmology. 2002;109(1):143-5.
25. Erdol H, Kola M, Turk A. Optical coherence tomography findings in a child with posterior scleritis.Eur J
Ophthalmol. 2008;18(6):1007-10.
26. Fong LP, Sainz de la Maza M, Rice BA, et al.
Immunopathology of scleritis. Ophthalmology. 1991;
98(4):472-9
27. Di Girolamo N, Lloyd A, McCluskey P, et al. Increased
expression of matrix metalloproteinases in vivo in scleritis
tissue and in vitro in cultured human scleral fibroblasts. Am
J Pathol. 1997;150(2):653-66.
28. Young RD, Watson PG. Microscopical studies of
necrotizing scleritis. II. Collagen degradation in the scleral
stroma. Br J Ophthalmol. 1984;68(11):781-9.
29. Pavesio CE, Meier FM. Systemic disorders associated
with episcleritis and scleritis. Curr Opin Ophthalmol. 2001;
12(6):471-8.
30. Riono WP, Hidayat AA, Rao NA. Scleritis: a
clinicopathologic study of 55 cases. Ophthalmology.
1999;106(7):1328-33.
31. Velasco e Cruz AA, Chahud F, Feldman R, Akaishi
PM. Posterior scleral tuberculoma: case report. Arq Bras
Oftalmol. 2011;74(1):53-4.
32. Babu K, Kini R, Mehta R. Scleral nodule and bilateral
disc edema as a presenting manifestation of systemic sarcoidosis. Ocul Immunol Inflamm. 2010;18(3):158-61.
33. Puech C, Gennai S, Pavese P, et al. Ocular manifestations of syphilis: recent cases over a 2.5-year period.
Graefes Arch Clin Exp Ophthalmol. 2010;248(11):1623-9.
34. Bhat PV, Jakobiec FA, Kurbanyan K, et al. Chronic
herpes simplex scleritis: characterization of 9 cases of
an underrecognized clinical entity.Am J Ophthalmol.
2009;148(5):779-789.
35. Kaplan-Messas A, Barkana Y, Avni I, Neumann R.
Methotrexate as a first-line corticosteroid-sparing therapy
in a cohort of uveitis and scleritis. Ocul Immunol Inflamm.
2003;11(2):131-9.
36. Hillenkamp J, Kersten A, Althaus C, Sundmacher
R. Cyclosporin A therapy in severe anterior scleritis. 5
severe courses without verification of associated systemic
disease treated with cyclosporin A. Ophthalmologe. 2000;
97(12):863-9.
37. Iaccheri B, Androudi S, Bocci EB, et al. Rituximab
treatment for persistent scleritis associated with rheumatoid arthritis. Ocul Immunol Inflamm. 2010;18(3):223-5.
38. Chauhan S, Kamal A, Thompson RN, et al. Rituximab
for treatment of scleritis associated with rheumatoid arthri-
tis. Br J Ophthalmol. 2009;93(7):984-5.
39. Meehan K, Vollmer L, Sowka J. Intraocular pressure
elevation from topical difluprednate use. Optometry.
2010;81(12):658-62.
SUPERIOR LIMBIC
KERATOCONJUNCTIVITIS
Signs and Symptoms
Superior limbic keratoconjunctivitis
(SLK) was first described as a unique
clinical disorder by Dr. Frederick
Theodore in 1963.1 Individuals presenting with this condition typically
report symptoms of ocular discomfort, including burning, foreign-body
sensation or non-descript pain.1,2
Additionally, complaints of photophobia and excessive tearing may be
described. Visual acuity is usually not
affected. SLK predominantly affects
women between the ages of 30 and 55
years.3
Gross clinical signs often include
mild lid swelling and pseudoptosis as
well as blepharospasm. Inspection of the
ocular surface in SLK reveals a sectoral
redundancy of the superior bulbar conjunctiva, with corresponding injection
and inflammation. The limbal margin
of the cornea may be inflamed as well.
Eversion of the upper lid reveals a uniform papillary hypertrophy along the
tarsus, which may be mild to marked.
Vital dye staining is characteristic in
SLK, with patients displaying punctate
epithelial disruption of the affected
region; this is evident with both sodium
fluorescein dye as well as rose bengal
or lissamine green solutions.2 Filament
accumulation in the tear film is also
common, being encountered in about
half of all patients with SLK. The
condition is typically bilateral but often
asymmetric. In most instances, the diagnosis of SLK is made solely based upon
the characteristic presentation. Recently,
laser scanning confocal microscopy has
been applied to the study of SLK in an
effort to more thoroughly clarify the
JUNE 15, 2012
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CONJUNCTIVA & SCLERA
pathophysiological mechanisms; the
correlation of in vivo confocal microscopy with more conventional testing
methods is quite high.4 Such testing
may be beneficial in cases that are not
clinically evident, have atypical histories
or fail to respond to aggressive therapy.5
Pathophysiology
The precise etiology and pathogenesis of SLK remains controversial.4-6
The most widely accepted theory today
holds that SLK results from conjunctival redundancy and soft-tissue microtrauma.7,8 Mechanical irritation occurs in
the superior limbal region as loose conjunctival tissue rubs against the limbus
during the blinking process. Research
has shown that this repeated trauma
causes damage, injury and inflammation, as represented by increased levels of
expressed matrix metalloproteinases.9 In
biopsy specimens of the superior tarsal
conjunctiva, patients with SLK display
infiltration of polymorphonuclear leukocytes, lymphocytes and plasma cells.3 In
years past, additional laboratory confirmation has been obtained from scrapings
of the affected superior bulbar conjunctivae, demonstrating the presence of keratinized, acanthotic epithelial cells.6
Several anatomical factors seem to
predominate in SLK, particularly tight
lids and prominent globes.1,2 These findings are consistent with the aforementioned mechanical theory of pathogenesis. Another theory implicates local tear
deficiency to the superior keratoconjunctiva. Researchers have proposed that this
deficiency results in significantly reduced
levels of vital tear-based nutrients to
the affected region as well as increased
mechanical friction from the superior
lid.8 An autoimmune etiology has been
considered, based upon the pattern of
the disorder (i.e., exacerbations and
remissions) the female predominance
of the disorder, and an association with
thyroid disease and other autoimmune
diseases. In fact, SLK is considered to be
Superior limbic keratoconjunctivitis.
a strong prognostic indicator for thyroid
eye disease.10
Management
A great many treatment modalities
have been employed in the management
of SLK, though few have been found
to be truly and consistently effective.
Therapy using a wide variety of topical
pharmaceutical agents has been attempted. Antibiotics and corticosteroids have
been found to be essentially ineffective in
this condition. Other preparations have
demonstrated limited success; among
these are vitamin A eyedrops, topical
mast cell stabilizers (e.g., 4% cromolyn
sodium, 0.1% lodoxamide tromethamine, and 0.025% ketotifen fumarate),
autologous serum, n-acetylcysteine, and
0.5% cyclosporine A eyedrops.3,8,11-16
Bandage contact lenses have been used
both with and without drug therapy,
in an effort to alleviate the mechanical irritation of SLK.17,18 Occlusion
of the superior puncta/canaliculi may
also be beneficial in this condition.2,19
Additionally, injectable agents such as
botulinum toxin A (to induce temporary ptosis) and triamcinolone (injected
supratarsally to diminish lid inflammation and lid-globe contact) have been
used with some success.18,20
More invasive therapies seek to
eradicate the dysfunctional conjunctiva
and replace it with new, healthy tissue. Silver nitrate solution (0.5% to
1.0%) applied topically to the superior
bulbar and tarsal conjunctivae was at
one time the preferred therapy for this
condition, and is still used to some
degree today.21 Silver nitrate serves
as a chemical form of cauterization;
unfortunately, there is a significant
chance of iatrogenic burns with this
technique, and even when applied correctly recurrences have been known to
occur.21,22 Chemocautery can also be
achieved by freezing the tissue with
liquid nitrogen (i.e., cryotherapy).23
Surgical options for SLK include thermal cauterization, conjunctival recession and resection.24,25
Clinical Pearls
• SLK of Theodore must be differentiated from contact lens-induced
SLK (CL-SLK), a condition that is
occasionally observed in young, otherwise healthy hydrogel lens wearers.
Solution hypersensitivity as well as
poorly fitted lenses have been implicated as the main contributory factors.
The typical presentation of this entity
consists of increasing contact lens
intolerance, superior tarsal and bulbar injection and significant superior
corneal staining with stromal hazing.
Corneal involvement may be noted
as far inferiorly as the superior pupillary margin. Treatment for CL-SLK
consists of temporarily discontinuing
contact lens wear, along with the liberal
use of preservative-free ocular lubricants. Upon resolution, contact lenses
should be refit and a preservative-free
care system should be employed.
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001_ro0612_hndbk.indd 17
17A
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• Past studies have demonstrated a
very high correlation between SLK and
systemic thyroid disease, on the order of
65%.26 Other conditions such as rheumatoid arthritis and Sjögren’s syndrome
may also have similar associations. All
patients presenting with SLK should
be referred for a systemic evaluation,
including a serologic thyroid panel.
• Some sources consider SLK to be
the result of a localized, severe, superior
form of conjunctivochalasis. Laxity of
the distal conjunctiva (i.e., within the
fornix) leads to mechanical irritation and
inflammation of the proximal or limbal
conjunctiva. Surgical treatment to resect
only the lax area of the superior conjunctiva—similar to the procedure used
to treat conjunctivochalasis—has shown
promise in restoring the limbal tissues to
normal health within two weeks.24,27
• SLK can be chronic and recalcitrant. In attempting to manage
this disorder, the rule of thumb is to
employ topical agents such as mast
cell stabilizers or cyclosporine A in the
earliest stages, followed by noninvasive
procedures such as bandage contact
lenses or lacrimal occlusion therapy.
Injections, chemocautery, thermocautery and surgical intervention should
be considered only when these other
interventions have failed.
1. Theodore FH. Superior limbic keratoconjunctivitis. Eye
Ear Nose Throat Mon. 1963;42:25-8.
2. Kabat AG. Lacrimal occlusion therapy for the treatment
of superior limbic keratoconjunctivitis. Optom Vis Sci.
1998;75(10):714-8.
3. Sahin A, Bozkurt B, Irkec M. Topical cyclosporine a
in the treatment of superior limbic keratoconjunctivitis: a
long-term follow-up. Cornea. 2008;27(2):193-5.
4. Kojima T, Matsumoto Y, Ibrahim OM, et al. In vivo
evaluation of superior limbic keratoconjunctivitis using
laser scanning confocal microscopy and conjunctival impression cytology. Invest Ophthalmol Vis Sci.
2010;51(8):3986-92. Epub 2010 Apr 7.
5. Moshirfar M, Khalifa YM, Kuo A, et al. Ocular surface
squamous neoplasia masquerading as superior limbic
keratoconjunctivitis. Middle East Afr J Ophthalmol.
2011;18(1):74-6.
6. Theodore FH, Ferry AP. Superior limbic keratoconjunctivitis. Clinical and pathological correlations. Arch
Ophthalmol. 1970;84(4):481-4.
7. Cher I. Blink-related microtrauma: when the ocular
surface harms itself. Clin Experiment Ophthalmol.
2003;31(3):183-90.
18A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 18
8. Goto E, Shimmura S, Shimazaki J, Tsubota K.
Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea. 2001;20(8):807-10.
9. Sun YC, Hsiao CH, Chen WL, et al. Overexpression of
matrix metalloproteinase-1 (MMP-1) and MMP-3 in superior limbic keratoconjunctivitis. Invest Ophthalmol Vis Sci.
2011 1;52(6):3701-5.
10. Chavis PS. Thyroid and the eye. Curr Opin
Ophthalmol. 2002 Dec;13(6):352-6.
11. Ohashi Y, Kinoshita S, Hosotani S, et al. Vitamin A
eyedrops for superior limbic keratoconjunctivitis. Am J
Ophthalmol. 1988 May 15;105(5):523-7.
12. Confino J, Brown SI. Treatment of superior limbic
keratoconjunctivitis with topical cromolyn sodium. Ann
Ophthalmol. 1987;19(4):129-31.
13. Grutzmacher RD, Foster RS, Feiler LS. Lodoxamide
tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol. 1995;120(3):400-2.
14. Udell IJ, Guidera AC, Madani-Becker J. Ketotifen
fumarate treatment of superior limbic keratoconjunctivitis.
Cornea. 2002;21(8):778-80.
15. Wright P. Superior limbic keratoconjunctivitis. Trans
Ophthalmol Soc U K. 1972;92:555-60.
16. Perry HD, Doshi-Carnevale S, Donnenfeld ED,
Kornstein HS. Topical cyclosporine A 0.5% as a possible
new treatment for superior limbic keratoconjunctivitis.
Ophthalmology. 2003;110(8):1578-81.
17. Watson S, Tullo AB, Carley F. Treatment of superior
limbic keratoconjunctivitis with a unilateral bandage contact lens. Br J Ophthalmol. 2002;86(4):485-6.
18. Chun YS, Kim JC. Treatment of superior limbic keratoconjunctivitis with a large-diameter contact lens and
Botulinum Toxin A. Cornea. 2009;28(7):752-8.
19. Yang HY, Fujishima H, Toda I, et al. Lacrimal punctal
occlusion for the treatment of superior limbic keratoconjunctivitis. Am J Ophthalmol. 1997;124(1):80-7.
20. Shen YC, Wang CY, Tsai HY, Lee YF. Supratarsal
triamcinolone injection in the treatment of superior limbic
keratoconjunctivitis. Cornea. 2007;26(4):423-6.
21. Wilson FM, Ostler HB. Superior limbic keratoconjunctivitis. Int Ophthalmol Clin. 1986 Winter;26(4):99-112.
22. Laughrea PA, Arentsen JJ, Laibson PR. Iatrogenic
ocular silver nitrate burn. Cornea. 1985-1986;4(1):47-50.
23. Fraunfelder FW. Liquid nitrogen cryotherapy of
superior limbic keratoconjunctivitis. Am J Ophthalmol.
2009;147(2):234-238.e1.
24. Yokoi N, Komuro A, Maruyama K, et al. New surgical
treatment for superior limbic keratoconjunctivitis and its
association with conjunctivochalasis. Am J Ophthalmol.
2003;135(3):303-8.
25. Sun YC, Hsiao CH, Chen WL, et al. Conjunctival
resection combined with tenon layer excision and the
involvement of mast cells in superior limbic keratoconjunctivitis. Am J Ophthalmol. 2008;145(3):445-52.
26. Kadrmas EF, Bartley GB. Superior limbic keratoconjunctivitis. A prognostic sign for severe Graves ophthalmopathy. Ophthalmology. 1995;102(10):1472-5.
27. Kheirkhah A, Casas V, Esquenazi S, et al. New surgical approach for superior conjunctivochalasis. Cornea.
2007;26(6):685-91.
TOXIC CONJUNCTIVITIS
Signs and Symptoms
Toxic conjunctivitis, sometimes
referred to as toxic follicular conjunctivitis, results from ocular exposure to nox-
ious foreign substances.1-8 The exposure
may involve a new topical medication,
an old or chronically used medication or contact lens.3-6 Occasionally,
the reaction is seen in those starting or
undergoing glaucoma therapy.1-3 When
the toxic conjunctivitis is associated
with a prescribed topical medication, it
is sometimes called a medicamentosa
conjunctivitis. Cosmetics, moisturizers,
aerosolized colognes, other personal
hygiene products, household or automobile products or nickel can likewise
induce a toxic conjunctivitis when the
eye is exposed to these agents.7-10 Toxic
conjunctival reactions have also been
documented secondary to exposure to
bio-waste or toxins of organisms infesting the eye lashes or residing on the
eyelid (pthiriasis and molluscum).4,11 The
process may occur unilaterally or bilaterally, depending upon the exposure.
Clinical features of toxic conjunctivitis
include ocular itching, burning, tearing,
blepharospasm, as well as marked injection and chemosis of the bulbar conjunctiva.1-12 The most recognizable feature
is a pronounced follicular reaction
involving the inferior (and sometimes
superior) tarsus with a notable absence
of preauricular lymphadenopathy.2-5 A
variable keratopathy is often secondarily
present depending upon the amount of
direct exposure the cornea endured and
the severity of the conjunctival response.
In cases that are chronic, pannus formation may result.13
Pathophysiology
The inflammatory response is triggered by chemical messengers that are
released in response to an exposure to
undesirable foreign substances (antigens, immunogen, allergens).14-17 The
reaction is necessary and protective and
works to limit contact with the rest of
the anatomic region by creating boundaries. The response is also designed to
begin the process of eliminating the
antigen by activating the elements of
JUNE 15, 2012
6/1/12 3:12 PM
Toxic conjunctivitis.
hypersensitivity reactions or anaphylactic
reactions. These reactions occur when
immunoglobulin IgE comes into contact with a particular antigen or allergen
producing a cascade that results in sudden and massive degranulation of local
mast cells.21,22 Upon activation, through
high affinity IgE receptors, mast cells
can release up to 100% of their content
of preformed mediators stored in cytoplasmic secretory granules via compound
exocytosis.22
• Type II reactions involve the body’s
ability to distinguish itself from non-self.
Abnormalities in this element of the
system give rise to autoimmune disease.23
The mechanism that leads to autoimmunity is complex and not fully understood.23 Recently a team of researchers
has hypothesized that autoimmune
diseases are caused by two age-related
processes: (1) senescent cell accumulation
in the immune system and target tissue/
organ, (2) heterogeneous accumulation
of senescent cells in tissues/organs.22
Separately or combined, these two processes are being examined as the basis for
autoimmune diseases.22
• Type III reactions involve combinations of antigens and antibodies known
as immune complexes.24 Offending
triggers may be intrinsic (i.e., a protein
molecule) or extrinsic (e.g., a penicillin
molecule) and produce a significant tissue
response in an attempt to rid the area of
the invader. It is this incorrect regulation
of the complement system that causes
inflammation and targeting of selftissue.24 Examples of type III complex
disease include systemic lupus erythematosus and rheumatoid arthritis.24
• Type IV reactions—sometimes
referred to as cell-mediated hypersensitivity reactions involve T-lymphocytes
and lymphokines.20,21,25 The reaction is
classically delayed until sufficient antigens
are present to stimulate the chemical cascade. In the ocular tissues, these chemical
exchanges incite conjunctival and adnexal
vasodilation, chemosis, edema and lacrimation.20,21,25 Individuals experience
local pain, itching, swelling and irritation. The discharge produced is typically
serous and the conjunctival findings may
include follicles (hyperplasia of lymphoid
tissue within the eyelid stroma) and/or
papillae (hyperplastic palpebral conjunctival epithelium infiltrated by lymphocytes
and plasma cells).4
Management
Management of toxic conjunctivitis
is aimed at reducing symptoms and
speeding resolution of the inflammation.4 Of course, the first step is to
remove the offending agent if possible. Palliative treatment with cold
compresses works by producing natural
vasoconstriction, limiting the movement of released cytokines. Artificial
tear administration can help to mitigate
the event by coating the corneal epithelium, providing uniform cover for
underlying nerves exposed by keratopathy and diluting the foreign substance
and physically washing it away.4
The mast cell/histamine response can
pharmacologically be controlled with
topical and oral allergy medications.26-30
A topical combination mast cell stabilizer/antihistamine is the mainstay of
therapy. This includes drugs, such as
Patanol (olopatadine HCl 0.1%, Alcon),
Zaditor (ketotifen fumarate 0.025%,
Novartis), Elestat (epinastine HCl
0.05%, Inspire) and Optivar (azelastine
HCl 0.05%, MedPointe)—all of which
are indicated for b.i.d. dosing. Pataday
(olopatadine HCl 0.2%, Alcon) and
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001_ro0612_hndbk.indd 19
CONJUNCTIVA & SCLERA
the immune system.14-17 Toxic/allergic
conjunctivitis occurs when the body’s
immune system responds to an exposure
of a foreign substance around the eye
or adnexa.14-18 This response can be
innate or acquired.18,19 A variation of this
response is manifested when the body
responds hyperactively to exogenous
materials such as medicines, contact
lenses, contact lens solutions, dust, dander or viral shedding.14-18 Over-activity
of this type is commonly referred to as a
toxic or allergic reaction. With respect to
the eye and its adnexa, the result is toxic
conjunctivitis.
The key component to the ocular
allergic response is the mast cell.14-18
When a mast cell interacts with a specific allergen, the outer cell membrane
is altered, and it releases chemical
mediators into the surrounding tissues;
this process is referred to as mast cell
degranulation.14-18 The primary chemical
mediator is histamine, which is responsible for increased vascular permeability,
vasodilation, bronchial constriction and
increased secretion of mucus. Other preformed mediators such as tryptase, chymase, bradykinin, interleukin and heparin
contribute to the allergic response.14-18
Sustained allergic responses in some
bodily tissues can induce eosinophilmediated inflammation, which through
the release of prostaglandins and leukotrienes, may result in tissue remodeling
and damage.14-18 Antibody and/or T-cell
mediated mechanisms are involved.17
Predominantly allergic responses are
characterized by immunoglobulin E
(IgE), mast-cell-mediated mechanics.17 Chronic mast cell activation with
a eosinophil/T-lymphocyte-mediated
response is the hallmark of giant papillary
conjunctivitis, vernal keratoconjunctivitis and atopic keratoconjunctivitis.17
T-lymphocyte-mediated responses are
distinctive in contact ocular allergic processes.17 There are four recognized types
of hypersensitivity reactions.20,21
• Type I reactions are immediate
19A
6/4/12 2:30 PM
Lastacaft (alcaftadine, Allergan) add
convenience of administration and are
approved for once-a-day usage. Topical
non-steroidal anti-inflammatory drugs
(NSAIDs) may be added q.d. to q.i.d.,
depending upon the severity of the
occurrence, to provide mild analgesia
for patients with corneal compromise,
however they do little to address the histamine-mediated response. New agents
in this class such as Acuvail (ketorolac
tromethamine, Allergan) and Bromday
(bromfenac sodium hydrate, ISTA) can
be used off label (they are approved for
controlling postoperative inflammation
following cataract surgery), q.d. to provide increased comfort.30 Topical corticosteroids (e.g., Pred-Forte, Lotemax or
Durezol), which address the effects of
inflammation, may be desirable in severe
or highly symptomatic reactions, but
are generally not necessary. Oral antihistamines can be added if the reaction
involves the eyelids or adnexa.
Clinical Pearls
• Toxic conjunctivitis is a diagnosis
that can be made based primarily upon
the history and clinical course. Typically,
vision is unaffected despite the unruly
appearance. Even if left untreated, toxic
conjunctivitis often begins to resolve
within days, providing that the offending agent is identified and removed or
discontinued.
• Medicamentosa is a sub-category
of toxic conjunctivitis used to connote
a toxic reaction to the preservatives in
medications. A substantial keratitis is
the hallmark of the medicamentosa
response.
• While many patients choose to
self-treat allergic or toxic conjunctivitis
with topical decongestants (e.g., Vasocon
or Visine), these agents are not recommended. While decongestants may produce short-term vasoconstriction, hence
reducing hyperemia, the effects are
short-lived. In addition, these products
have been shown to actually induce toxic
20A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 20
conjunctivitis in a significant percentage
of patients, and they may cause even
more severe allergic responses such as
contact dermatitis.26 Advise patients to
avoid these over-the-counter remedies,
and instead recommend a prescriptionstrength topical allergy medication.
• The use of oral antihistamines for
purely ocular allergic responses, such
as toxic conjunctivitis, is less efficient.
Studies have shown that topical agents
provide more rapid relief than oral antihistamines alone.27,28 In addition, many
oral antihistamines (particularly the older
generation drugs such as Benadryl) can
induce central nervous system depression
(e.g., dizziness, drowsiness, etc.) as well
as antimuscarinic effects (e.g., dry mouth
and dry eyes, pupil dilation with possible
subsequent angle closure).29
1. Blondeau P, Rousseau JA. Allergic reactions to brimonidine in patients treated for glaucoma. Can J Ophthalmol
2002;37(1):21-6.
2. Coleiro JA, Sigurdsson H, Lockyer JA. Follicular conjunctivitis on Dipivefrin therapy for glaucoma. Eye 1988;
2(Pt 4):440-2.
3. Baudouin C. Allergic reaction to topical eyedrops. Curr
Opin Allergy Clin Immunol. 2005;5(5):459-63.
4. Rubuenstein JB, Jick SL. Disorders of the conjunctiva
and limbus. In: Yanoff M, Duker JS. Ophtalmology 2nd
ed. Philadelphia: Mosby; 2004:397-412.
5. Mantelli F, Lambiase A, Bonini S. A simple and rapid
diagnostic algorithm for the detection of ocular allergic
diseases. Curr Opin Allergy Clin Immunol. 2009;9(5):4716.
6. Radford CF, Minassian D, Dart JK, et al. Risk factors for nonulcerative contact lens complications in an
ophthalmic accident and emergency department: a casecontrol study. Ophthalmology. 2009;116(3):385-92.
7. Sliney DH. How light reaches the eye and its components. Int J Toxicol. 2002;21(6):501-9.
8. Ratnapalan S, Das L. Causes of eye burns in children.
Pediatr Emerg Care. 2011;27(2):151-6.
9. Hedberg Y, Midander K, Wallinder IO. Particles, sweat,
and tears: a comparative study on bioaccessibility of ferrochromium alloy and stainless steel particles, the pure
metals and their metal oxides, in simulated skin and eye
contact. Integr Environ Assess Manag. 2010;6(3):456-68.
10. Walsh ML, Smith VH, King CM. Type 1 and type
IV hypersensitivity to nickel. Australas J Dermatol.
2010;51(4):285-6.
11. Schornack MM, Siemsen DW, Bradley EA, et al.
Ocular manifestations of molluscum contagiosum. Clin
Exp Optom. 2006;89(6):390-3.
12. Mendes A, Madureira J, Neves P, et al. Chemical
exposure and occupational symptoms among
Portuguese hairdressers. J Toxicol Environ Health A.
2011;74(15-16):993-1000.
13. Dart J. Corneal toxicity: the epithelium and stroma in
iatrogenic and factitious disease. Eye. 2003;17(8):886-92.
14. Chigbu DI. The management of allergic eye dis-
eases in primary eye care. Cont Lens Anterior Eye.
2009;32(6):260-72.
15. Takamura E, Uchio E, Ebihara N, et al. Japanese
guideline for allergic conjunctival diseases. Allergol Int.
2011;60(2):191-203.
16. Jedrzejczak-Czechowicz M, Lewandowska-Polak A,
Jarzebska M, et al. Mast cell and eosinophil activation
during early phase of grass pollen-induced ocular allergic
reaction. Allergy Asthma Proc. 2011;32(1):43-8.
17. Leonardi A. The central role of conjunctival mast cells
in the pathogenesis of ocular allergy. Curr Allergy Asthma
Rep. 2002;2(4):325-31.
18. Black PN. Does atopy protect against enteric infections? Allergy. 2005;60(1):30-4.
19. Ueta M, Kinoshita S. Ocular surface inflammation mediated by innate immunity. Eye Contact Lens.
2010;36(5):269-81.
20. Friedmann PS, Lee MS, Friedmann AC, Barnetson
RS. Mechanisms in cutaneous drug hypersensitivity reactions. Clin Exp Allergy. 2003;33(7):861-72.
21. Pararajasegaram. Mechanisms of uveitis. In: Yanoff
M, Duker JS. Ophtalmology 2nd ed. Philadelphia: Mosby;
2004: 1105-1112.
22. Blank U. The mechanisms of exocytosis in mast cells.
Adv Exp Med Biol. 2011;716(1):107-22.
23. Manestar-Blazić T, Volf M. The dynamic of senescent cells accumulation can explain the age-specific
incidence of autoimmune diseases. Med Hypotheses.
2009;73(5):667-9.
24. Murray-Rust TA, Kerr FK, Thomas AR, et al.
Modulation of the proteolytic activity of the complement
protease C1s by polyanions: implications for polyanionmediated acceleration of interaction between C1s and
SERPING1. Biochem J. 2009;422(2):295-303.
25. Ton ić RJ, Lipozen ić J, Martinac I, et al. Immunology
of allergic contact dermatitis. Acta Dermatovenerol Croat.
2011;19(1):51-68.
26. Soparkar CN, Wilhelmus KR, Koch DD, et al. Acute
and chronic conjunctivitis due to over-the-counter
ophthalmic decongestants. Arch Ophthalmol. 1997;
115(1):34-8.
27. Lanier BQ, Gross RD, Marks BB, et al. Olopatadine
ophthalmic solution adjunctive to loratadine compared
with loratadine alone in patients with active seasonal
allergic conjunctivitis symptoms. Ann Allergy Asthma
Immunol. 2001;86(6):641-8.
28. Abelson MB, Welch DL. An evaluation of onset and
duration of action of Patanol (olopatadine hydrochloride
ophthalmic solution 0.1%) compared to Claritin (loratadine 10 mg) tablets in acute allergic conjunctivitis in the
conjunctival allergen challenge model. Acta Ophthalmol
Scand Suppl. 2000;(230):60-3.
29. Simons FE. Advances in H1-antihistamines. N Engl J
Med. 2004;351(21):2203-17.
30. Mishra GP, Tamboli V, Jwala J, et al. Recent patents
and emerging therapeutics in the treatment of allergic
conjunctivitis. Recent Pat Inflamm Allergy Drug Discov.
2011;5(1):26-36.
VERNAL
KERATOCONJUNCTIVITIS
Signs and Symptoms
Vernal conjunctivitis (VKC) is
chronic allergic/inflammatory disorder
that affects the superior tarsal and lim-
JUNE 15, 2012
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Cobblestone papillae in VKC.
25% of VKC patients the disease smolders year-round, without any remission.2 Males are predominantly affected
by a ratio of 3.3:1.5 The average age
of disease onset is seven years, though
patients may range from three to 25
years.5,6 In most cases, a personal or
family history of allergic disease (seasonal rhinitis, asthma, atopic eczema) can
be elicited; one-third of patients exhibit
multiple atopic disorders.2
Pathophysiology
Unlike the more common seasonal
allergic conjunctivitis, VKC is not simply
a Type I, IgE-mediated hypersensitivity disorder.1 Numerous autoimmune
cells—including mast cells, eosinophils
and lymphocytes—as well as chemical mediators have been identified in
the tears, conjunctiva and the serum of
patients with VKC.7 Bonini and colleagues suggest that VKC is “a Th2driven mechanism…similar to that of
asthma.”2 Mast cells and basophils spur
the immediate response via histamine
release and by recruiting inflammatory
lymphocytes and eosinophils.7 This
results in the release of toxic cell mediators with ensuing ocular surface inflammation and tissue damage.2
The etiology of pathologic sequelae
in VKC is multifactorial, involving
tissue inflammation, infiltration and
remodeling. Vernal papillae represent
hyperplastic conjunctival epithelium
infiltrated by lymphocytes and plasma
cells; these may form on the upper
tarsal plate or at the limbal margin.
Histopathological studies of conjunctival specimens from chronic VKC
patients reveals thickening of the conjunctiva with proliferation of collagen,
capillaries and other cellular components.8 Horner-Trantas dots, noted
in the peripheral cornea, are actually
focal accumulations of degenerated
eosinophils and desquamated epithelial
cells, liberated by the inflammatory
process.9 Vernal shield ulcers are composed of abnormal mucus, fibrin and
serum, deposited within the superficial
epithelium as a grayish plaque. By a
combination of corrosive inflammatory
chemicals (e.g., major basic protein)
and the mechanical rubbing of the
papillae over the cornea, epithelial erosions may occur; this represents the
source of the shield ulcer in VKC.2,4
Management
A clinical staging strategy has been
proposed for patients with VKC; this
allows for proper differentiation and
appropriate therapy, based upon the
severity of the disease.10 Features of
the condition are graded on a zeroto-five scale, in categories including patient symptoms, conjunctival
hyperemia, conjunctival secretion (i.e.,
discharge), papillary reaction, HornerTrantas dots and corneal involvement
(e.g., punctate keratitis or erosion). It
should be noted however that VKC
can be extremely variable; hence, the
proposed scale is not necessarily a
progression, but rather a classification
that may be applied at any point in
the course of the disease process.
For patients with mild to moderate VKC (Grade 1 and 2), treatment
consists primarily of topical anti-allergy
drugs, using either a single action (e.g.,
antihistamine or mast cell stabilizer)
or a multiaction mechanism. Though
there are many options in this family
of medications, newer drugs such as
Pataday (olopatadine 0.2%, Alcon) or
0.25% Lastacaft (alcaftadine, Allergan)
afford patients the greatest potential for
symptomatic relief at a dosing of just
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 21
CONJUNCTIVA & SCLERA
bal palpebral conjunctiva. It presents
classically with severe ocular itching,
photophobia, tearing, conjunctival
redness and a thick, ropy mucous discharge. The condition is bilateral in
98% of cases, though asymmetry may
be observed.1,2 The hallmark sign of
VKC is the presence of extreme papillary hypertrophy on the upper tarsal
conjunctiva and/or at the limbal margin. When large “cobblestone” papillae
are seen upon lid eversion, the condition is described as the tarsal form
of VKC; by contrast, when multiple
gelatinous elevations are seen at the
superior corneoscleral interface, this
constitutes the limbal form of VKC.1
Horner-Trantas dots (focal, white
limbal infiltrates), usually located at the
superior corneal margin, are another
feature of the limbal form of this disorder. Additional corneal involvement
may be manifested as punctate keratitis
and, in severe cases, corneal shield
ulcers, which are typically encountered
in the superior one-third of the cornea.1 Less commonly, pseudogerontoxon is seen in association with VKC.
This rare finding may be seen as a
local, grayish-white lipid deposit occurring in the peripheral cornea of patients
with the limbal form of VKC.3,4
Pseudogerontoxon is often confused
with arcus senilis, a condition seen in
older individuals that is characteristically bilateral and secondary to cholesterol
deposition in the cornea as a result of
dyslipidemia. Pseudogerontoxon is only
noted in young patients, is unrelated to
serum lipid levels and may be unilateral
as a result of allergic pathophysiology.4
In patients with VKC, acuity may be
mildly to severely affected, depending
upon the type and extent of corneal
involvement.
VKC tends to be a seasonal disease
with a skewed geographic distribution,
occurring primarily during the spring
and summer months in warm and dry
geographic regions; however, in about
21A
6/1/12 3:15 PM
once daily. Other medications in these
categories (e.g., azelastine, emadastine,
epinastine, ketotifen and lodoxamide)
require dosing from two to four times
daily for the same level of relief. In
severe cases of VKC, the use of topical
corticosteroids becomes more critical.
Grade 3 (i.e., severe) VKC denotes the
use of pulsed steroids, over and above
the use of the topical anti-allergy drugs
employed daily. At the present time,
Alrex (loteprednol etabonate 0.2%,
Bausch + Lomb) is the only topical steroid specifically approved by the U.S.
Food & Drug Administration for allergic disorders of the eye, but other steroids may be just as effective, including
prednisolone acetate, fluorometholone
or difluprednate. For chronic, severe
VKC, the use of topical cyclosporine
A (CsA) may be attempted in lieu of
corticosteroids and in conjunction with
topical antihistamines. CsA has the
capacity to control ocular inflammation
by blocking Th2 lymphocyte proliferation and interleukin production; to a
lesser degree, it can also inhibit histamine release and the recruitment of
eosinophils within the conjunctiva.10-12
Clinical studies and personal experience have shown a distinct benefit to
topical CsA (i.e., Restasis, Allergan) in
VKC patients who do not respond to
conventional treatment options or who
are at risk for complications associated with prolonged steroid therapy.13
Experimental treatment with immunomodulatory agents, including tacrolimus and omalizumab, have shown
promise for recalcitrant VKC.14,15
At all levels, the adjunctive use of
lubricant ophthalmic drops may help
to enhance comfort by increasing the
barrier function of the tear film.10
Selection from among the many available artificial tear products should be
guided by the severity of symptoms
and the extent of corneal compromise.
Gel-forming solutions and higher
viscosity agents should be reserved
22A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 22
for those with more severe forms of
keratitis. Additional therapy for VKC
may include topical cycloplegia (e.g.,
0.25% scopolamine b.i.d.) and broadspectrum antibiotic prophylaxis (e.g.,
tobramycin 0.3% q.i.d. or moxifloxacin
0.5% t.i.d.) for associated shield ulcers.
Mucolytics such as 5% n-acetylcysteine
t.i.d. to q.i.d. may be helpful in eliminating the ropy, mucous discharge.
Patients using topical medication
for VKC should be re-evaluated at one
week and closely monitored thereafter.
Patients using topical steroids for more
than two weeks should have periodic
ocular health assessments, including
tonometry to ensure that intraocular
pressure remains normal. Shield ulcers
need to be followed every 24 to 72
hours until re-epithelialization ensues.
Clinical Pearls
• Cobblestone papillae in VKC
are substantially larger and less uniform in size and shape than papillae
associated with giant papillary conjunctivitis (GPC) or seasonal allergic
conjunctivitis. Additionally, cobblestone papillae may be scant in number; these authors have seen patients
with VKC who had between one
and five papillae, yet were exceedingly symptomatic.
• The term “shield ulcer” is something of a misnomer, in that the name
suggests an infectious etiology. The
shield ulcers in VKC are sterile in
nature, and result from mechanical
forces rather than microbial organisms.
Also, an “ulcer,” by definition, involves a
loss of tissue beyond the surface epithelium; those conditions that involve only
the epithelium are more appropriately
termed “erosions.”
• Evidence suggests that VKC often
subsides with the onset of puberty.
However, some individuals may require
therapeutic intervention well into their
teens or early twenties to control the
course of the disease.
• While oral antihistamines may
reduce some of the generalized symptoms associated with ocular allergy,
they have little or no effect on VKC.7
Topical multiaction (i.e., antihistamine
and mast cell stabilizer) anti-allergy
compounds deliver far greater concentrations of the drugs to the ocular
tissues, and have less potential systemic
side effects. In contrast, the use of oral
non-steroidal, anti-inflammatory agents,
particularly aspirin therapy, has been
shown to be effective in reducing some
of the signs and symptoms of VKC.16
1. Kumar S. Vernal keratoconjunctivitis: a major review.
Acta Ophthalmol. 2009;87(2):133-47.
2. Bonini S, Bonini S, Lambiase A, et al. Vernal keratoconjunctivitis revisited: a case series of 195 patients with
long-term follow up. Ophthalmology. 2000;107(6):115763.
3. Jeng BH, Whitcher JP, Margolis TP.
Pseudogerontoxon. Clin Experiment Ophthalmol.
2004;32(4):433-4.
4. Read SA, Swann PG. Unilateral pseudogerontoxon.
Clin Exp Optom. 2009;92(2):150-3.
5. Leonardi A, Busca F, Motterle L, et al. Case series of
406 vernal keratoconjunctivitis patients: a demographic
and epidemiological study. Acta Ophthalmol Scand.
2006;84(3):406-10.
6. Butrus S, Portela R. Ocular allergy: diagnosis and
treatment. Ophthalmol Clin North Am. 2005;18(4):48592, v.
7. Bonini S, Coassin M, Aronni S, Lambiase A. Vernal
keratoconjunctivitis. Eye (Lond). 2004;18(4):345-51.
8. Leonardi A. Vernal keratoconjunctivitis: pathogenesis
and treatment. Prog Retin Eye Res. 2002;21(3):319-39.
9. Hall A, Shilio B. Vernal keratoconjunctivitis. Community
Eye Health. 2005;18(53):76-8.
10. Bonini S, Sacchetti M, Mantelli F, Lambiase A.
Clinical grading of vernal keratoconjunctivitis. Curr Opin
Allergy Clin Immunol. 2007;7(5):436-41.
11. Pucci N, Novembre E, Cianferoni A, et al. Efficacy
and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol. 2002;89(3):298303.
12. Cetinkaya A, Akova YA, Dursun D, Pelit A. Topical
cyclosporine in the management of shield ulcers.
Cornea. 2004;23(2):194-200.
13. Lambiase A, Leonardi A, Sacchetti M, et al. Topical
cyclosporine prevents seasonal recurrences of vernal
keratoconjunctivitis in a randomized, double-masked,
controlled 2-year study. J Allergy Clin Immunol.
2011;128(4):896-897.e9.
14. Taddio A, Cimaz R, Caputo R, et al. Childhood
chronic anterior uveitis associated with vernal keratoconjunctivitis (VKC): successful treatment with topical
tacrolimus. Case series. Pediatr Rheumatol Online J.
2011;9(1):34.
15. Sánchez J, Cardona R. Omalizumab. An option in
vernal keratoconjunctivitis? Allergol Immunopathol (Madr).
2011 Oct 3. [Epub ahead of print]
16. Anwar MS. The role of aspirin in vernal keratoconjunctivitis. J Coll Physicians Surg Pak 2003;13(3):178-9.
JUNE 15, 2012
6/1/12 3:15 PM
CORNEA
Signs and Symptoms
Contact lens-induced or contact lensassociated acute red eye (CLAARE)
(sometimes known as contact lens over
wear or immobile lens syndrome) is a
descriptive term that connotes a characteristic clinical history, clinical presentation and a broad range of specific
ocular findings connected with contact
lens over exposure. The classic scenario
involves a contact lens patient sleeping
in their lenses who, upon awakening,
experiences unilateral ocular pain (e.g.
foreign body sensation), tearing, variably decreased vision and photophobia.
Biomicroscopic inspection typically
reveals moderate to severe conjunctival
and limbal hyperemia with the potential
for diffuse or focal subepithelial infiltrates in the midperipheral or peripheral
cornea.1,2 Associated clinical signs may
include corneal edema and mild to
moderate blepharospasm, while pronounced lid edema, corneal epitheliopathy, and anterior chamber reaction are
notably absent.
The history of patients with
CLAARE can also be exceedingly
variable. While most resources cite
cases involving hydrogel lenses, the
condition may be encountered with
both daily wear and extended wear
materials, including silicone hydrogels.3
Rigid lenses have also been implicated.
There is no apparent association with
any specific type of care system, nor is
poor contact lens fit or hygiene necessarily a factor, although these may be
encountered in some patients. Likewise,
some individuals may present with an
immobile, “stuck-on” lens, but this is
not universal.
tion of the contact lens, contact lens
solution, lens case or other accessories.4
Gram-negative bacteria appear to be
the most common culprit, particularly Pseudomonas, Haemophilus and
Serratia species.4,5 These strains differ
from those that typically cause corneal
ulcers; they release endotoxins that
recruit inflammatory cells via the limbal
vasculature into the corneal stroma.5
Earlier theories regarding the etiology
of CLAARE suggested that mechanical
factors such as lens-induced hypoxia or
corneal microtrauma were implicated
in this disorder.6,7 More recent research
confirms specific bacterial strains as the
primary causative agent.1,3,4,8
Nomenclature and classification
of corneal infiltrative events includes
CLAARE and other descriptivelynamed conditions such as contact
lens-induced peripheral ulcer (CLPU),
contact lens-induced keratitis (CLIK),
infiltrative keratitis, sterile corneal
ulcer and marginal keratitis.8 At least
one critic believes these classification
schemes to be arbitrary with significant overlap and confusion.8 Corneal
surgeons, contact lens specialists and
general eye care providers may likely
continue to disagree on terminology but
in all likelihood these conditions fall on
a continuum with multiple etiologic factors and variable degrees of clinical morbidity. The one entity that is distinct
from these other conditions is microbial
keratitis (MK). MK connotes a focal
area of pathogenic invasion and replication rather than an immune response to
surface toxins.
Pathophysiology
CLAARE is believed to represent
an immune reaction of the cornea that
is associated with bacterial coloniza-
Contact lens-associated acute red eye
(CLAARE).
Management
Since the contact lens represents the
primary antigen in CLAARE, the initial therapeutic measure must involve
cessation of lens use. Typically, patients
are advised to remain without contact
lenses until the infiltrates resolve. This
may require several days or even weeks.
Concurrent lubrication with topical
lubricants helps to provide palliative
relief of symptoms, and lid hygiene
therapy is beneficial to reduce resident
bacterial populations. In mild presentations, these simple measures may
be sufficient to enable full resolution
of the condition. However, for more
severe or symptomatic cases, the use
of pharmaceutical agents can help to
significantly speed resolution and ameliorate discomfort. Prophylactic antibiotics are helpful in addressing bacterial overgrowth that is at the heart of
CLAARE. Broad-spectrum antibiotics
with gram-negative coverage are preferable, such as aminoglycosides (gentamicin, tobramycin) or fluoroquinolones
(moxifloxacin, gatifloxacin, besifloxacin
or levofloxacin). Topical corticosteroids are also beneficial in cases of
CLAARE, as they rapidly mitigate
symptoms and corneal infiltrates. Since
the condition is superficial, virtually
any corticosteroid may be used, including prednisolone, dexamethasone,
fluorometholone, loteprednol or difluprednate. Perhaps the most effective
and easiest therapeutic regimen is to
use an antibiotic-corticosteroid combination, such as TobraDex ST (tobramycin, dexamethasone, Alcon) or Zylet
(tobramycin, lotoprednol, Bausch +
Lomb), on a q.i.d. basis. Cycloplegia is
rarely necessary as deep inflammation is
highly atypical; however, in such cases,
a mild agent such as homatropine 5%
b.i.d. may be employed. Reevaluation
should be performed every 24 to 48
hours as patients remain on therapy.
After resolution, refitting of the contact
lenses should be considered.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 23
CORNEA
CONTACT LENS-ASSOCIATED
ACUTE RED EYE (CLAARE)
23A
6/1/12 3:16 PM
Clinical Pearls
• Many clinicians use the term
“contact lens overwear syndrome” or
“tight lens syndrome” interchangeably
with CLAARE to describe an acutely
inflamed eye associated with excessive
or abusive contact lens wear. These designations imply a purely hypoxic stress
situation, which typically presents with
punctate epitheliopathy and, in some
cases, a corneal/conjunctival indentation corresponding to the edge of the
entrapped lens. CLAARE, by definition
involves an immune response to bacterial pathogens.
• CLAARE must also be carefully
differentiated from microbial keratitis.
True bacterial corneal ulcers will always
show an overlying epithelial defect in
association with focal corneal infiltration, usually in a 1-to-1 ratio. If a definitive diagnosis cannot be made, treat
the condition as microbial keratitis and
prescribe a fluoroquinolone antibiotic
frequently for at least 24 hours before
considering a topical corticosteroid.
• While CLAARE can occur with
virtually any type of contact lens or
wearing regimen, it has been shown that
extended-wear significantly increases its
risk. Further, patients who have endured
one episode are more susceptible to
repeat occurrences.10,11 These individuals should ideally be reassigned to a
lower-risk regimen, such as daily wear,
gas permeable, or ideally, daily disposable lenses.
1. Sweeney DF, Jalbert I, Covey M, et al. Clinical characterization of corneal infiltrative events observed with soft
contact lens wear. Cornea. 2003;22(5):435-42.
2. Patrick A, Edmonson W (eds). AOCLE Living Library:
Contact Lens-Induced Acute Red Eye (CLARE).
November 18, 2001. Available at: www.opt.indiana.edu/
aocle/livlib/clare.htm. Accessed December 26, 2011.
3. Dumbleton K. Adverse events with silicone hydrogel
continuous wear. Cont Lens Anterior Eye. 2002;25(3):13746.
4. Szczotka-Flynn LB, Pearlman E, Ghannoum M.
Microbial contamination of contact lenses, lens care
solutions, and their accessories: a literature review. Eye
Contact Lens. 2010;36(2):116-29.
5. Holden BA, La Hood D, Grant T, et al. Gram-negative
bacteria can induce contact lens related acute red eye
(CLARE) responses. CLAO J. 1996;22(1):47-52.
24A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 24
6. Binder PS. The physiologic effects of extended wear
soft contact lenses. Ophthalmology. 1980;87(8):745-9.
7. Holden BA. The Glenn A. Fry Award lecture 1988: the
ocular response to contact lens wear. Optom Vis Sci.
1989;66(11):717-33.
8. Efron N, Morgan PB. Rethinking contact lens associated keratitis. Clin Exp Optom. 2006;89(5):280-98.
9. Netland PA. Tight lens syndrome with extended wear
contact lenses. CLAO J. 1990 Oct-;16(4):308.
10. Sweeney DF, Grant T, Chong MS, et al. Recurrence
of acute inflammatory conditions with hydrogel extended
wear. Invest Ophthalmol Vis Sci. 1993;34:Abstract 1008.
11. Sweeney DF, Stern J, Naduvilath T, Holden BA.
Inflammatory adverse event rates over 3 years with
silicone hydrogel lenses. Invest Ophthalmol Vis Sci.
2002;43:E-Abstract 976.
DISCIFORM KERATITIS
Signs and Symptoms
Patients with disciform keratitis will
present with a moderately painful eye
that is both tearing and photophobic.
Vision may be modestly reduced, particularly if the visual axis is involved;
however, the vision reduction does not
have to be dramatic. Often, the patient
will have a history of prior ocular or
systemic outbreak of either herpes
simplex or zoster.1-8 The patient may
have had a recent outbreak of epithelial
herpes simplex or may concurrently have
a dermatological outbreak of herpes
zoster. However, a history of herpes is
not mandatory as disciform keratitis is
a finding that may also occur secondary
to Acanthamoeba and other protozoan
infection, cat scratch disease, LASIK
surgery, Kawasaki disease, smallpox and
smallpox immunization, among other
numerous etiologies.9-17
There will be modest conjunctival
injection as well as a mild anterior
chamber reaction. While the anterior
chamber reaction is typically mild, there
may be a disproportionately large rise in
intraocular pressure. The key diagnostic
sign is a disc-shaped area of focal corneal stromal edema that may be either
peripheral or central.18 There may be
a surrounding ring of infiltrate known
as a Wesley ring at the junction of the
microbial antigen and host immune
reaction. There typically is no stromal
vascularization and the epithelial integrity remains intact. In some cases, there
may be folds in Descemet’s membrane.
Pathophysiology
Disciform keratitis is a delayed
hypersensitivity reaction involving the
corneal stroma. In disciform keratitis,
corneal endothelial cells demonstrate
significant increases of variation in
cell size (polymegathism) and shape
(pleomorphism) when compared
to the cells in the fellow unaffected
eyes.19 There is a granulomatous reaction within Descemet’s membrane,
Bowman’s membrane and the corneal
stroma.14,20,21
Disciform keratitis results from an
antibody-mediated response to microbial antigens, typically viral, within the
corneal stroma.21-23 It must be stressed
that these are inactive antigens and that
the edematous response is immunological. Also, there is no active stromal
infection. As such, antiviral medications
serve no direct therapeutic benefit, but
may be beneficial prophylactically in the
case of herpetic disease.4,24,25
Management
Cycloplegic agents such as homatropine 5% or scopolamine 0.25% b.i.d.,
along with copious topical lubrication
should be used for patients with disciform keratitis. In addition, topical
corticosteroids must be employed to
resolve the condition. Excellent choices
include Pred forte (prednisolone acetate
1%, Allergan), Durezol (difluprednate
emulsion, Alcon) and Lotemax (loteprednol etabonate 0.5%, Bausch +Lomb)
q.i.d. (or greater, depending upon the
severity). The lowest dose of topical steroids that will control the inflammation
should be used.
In that there is increased corneal
thickness due to corneal edema in disciform keratitis, therapeutic responses can
be monitored through patient symptoms, biomicroscopic appearance and
JUNE 15, 2012
6/1/12 3:16 PM
Clinical Pearls
• Disciform keratitis is a finding
that occurs secondary to some causative
agent and is not truly a diagnosis. The
causative agent should be identified, if
possible. More often than not, herpes
virus is the causative agent.
• If a patient manifests a disc-shaped
area of focal stromal edema, it is disciform keratitis.
• Cases of disciform keratitis caused
by herpes virus are typically mild and best
managed with topical cycloplegia, lubrication and low doses of topical steroids.
• When a case of disciform keratitis
in discovered, probe for a history of
herpes simplex or zoster. This may
involve serologic testing, as there have
been cases of disciform keratitis secondary to herpes simplex in patients
who had never previously had an epithelial outbreak. Similarly, there have
been instances where a patient experienced disciform keratitis secondary to
herpes zoster without ever having had a
previous dermatological outbreak. This
particular entity has been termed “herpes zoster sine herpete.”35
• As disciform keratitis is immune
modulated and there is no active microbial infection present, any use of antibiotic and antiviral medications would
be prophylactic not therapeutic. Antiinflammatory therapy is the mainstay.
1. Saini JS, Agarwala R. Clinical pattern of recurrent herpes simplex keratitis. Indian J Ophthalmol. 1999;47(1):114.
2. Choong YF, Hawksworth NR. Spontaneous reduction
in myopic correction following varicella disciform stromal
keratitis. Br J Ophthalmol. 2002;86(8):939-40.
3. Holland EJ, Schwartz GS. Classification of herpes simplex virus keratitis. Cornea. 1999;18(2):144-54.
4. Collum LM, Power WJ, Collum A. The current management of herpetic eye disease. Doc Ophthalmol.
1992;80(2):201-5.
5. Wilhelmus KR, Hamill MB, Jones DB. Varicella disciform
stromal keratitis. 5: Am J Ophthalmol. 1991;111(5):57580.
6. de Freitas D, Sato EH, Kelly LD, et al. Delayed onset of
varicella keratitis. Cornea. 1992;11(5):471-4.
7. Yu DD, Lemp MA, Mathers WD, et al. Detection of
varicella-zoster virus DNA in disciform keratitis using
polymerase chain reaction. Arch Ophthalmol. 1993
Feb;111(2):167-8.
8. Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985;92(3):316-24.
9. Demirci G, Ay GM, Karabas LV, et al. Acanthamoeba
keratitis in a 5-year-old boy without a history of contact
lens usage. Cornea. 2006;25(3):356-8.
10. Gabler B, Linde HJ, Reischl U, et al. Disciform keratatis caused by Bartonella henselae infection: detection of a
rare ocular complication of cat-scratch disease with PCR.
Klin Monatsbl Augenheilkd. 2000;217(5):299-302.
11. Dada T, Sharma N, Vajpayee RB, et al. Sterile
central disciform keratopathy after LASIK. Cornea.
2000;19(6):851-2.
12. Kadyan A, Choi J, Headon MP. Disciform keratitis and
optic disc swelling in Kawasaki disease: an unusual presentation. Eye. 2005 Sep 16; [Epub ahead of print].
13. Semba RD. The ocular complications of smallpox and smallpox immunization. Arch Ophthalmol.
2003;121(5):715-9.
14. Mietz H, Font RL. Acanthamoeba keratitis with granulomatous reaction involving the stroma and anterior chamber. Arch Ophthalmol. 1997;115(2):259-63.
15. Offret H. Disciform keratitis and Kawasaki’s disease. J
Fr Ophtalmol. 1993;16(2):114-6.
16. Davis RM, Font RL, Keisler MS, et al. Corneal microsporidiosis. A case report including ultrastructural observa-
CORNEA
corneal pachymetry.26,27
As the main cause of disciform keratitis is typically herpes virus, topical antiviral medications should be used prophylactically if topical steroids are being
used to prevent a breakout of epithelial
dendritic keratitis. Topical trifluridine
dosed q.i.d. is typically sufficient. While
there are no studies on prophylactic use,
topical Zirgan (ganciclovir gel, Bausch
+ Lomb) has been shown to be effective
in the management of herpes simplex
epithelial keratitis.28-30 It can be speculated that ganciclovir gel at four to five
times per day may provide prophylactic
coverage when a patient with disciform
keratitis secondary to herpetic disease is
being treated with topical steroids.
Should the epithelium ulcerate during topical steroid therapy, the steroid
should either be reduced or discontinued altogether until the epithelium
heals. In cases where topical antiviral
therapy is unavailable or not well tolerated, oral antiviral agents such as
acyclovir can provide prophylactic protection.24-34 Steroids should be slowly
tapered over several weeks in order to
avoid a rebound reaction. Some patients
will require topical steroids once daily
for prolonged periods and some patients
may require steroids indefinitely.
Disciform keratitis in herpes simplex.
tions. Ophthalmology. 1990;97(7):953-7.
17. Johns KJ, O’Day DM, Head WS, et al. Herpes simplex
masquerade syndrome: Acanthamoeba keratitis. Curr Eye
Res. 1987;6(1):207-12.
18. Wilhelmus KR, Sugar J, Hyndiuk RA, et al. Corneal
thickness changes during herpes simplex virus disciform
keratitis. Cornea. 2004;23(2):154-7.
19. Hirose N, Shimomura Y, Matsuda M, Corneal endothelial changes associated with herpetic stromal keratitis.
Jpn J Ophthalmol. 1988;32(1):14-20.
20. Mauriello JA Jr, McLean IW, Riddle PJ.
Granulomatous reaction to Bowman’s layer in herpetic
keratitis and band keratopathy. Can J Ophthalmol.
1995;30(4):203-7.
21. Holbach LM, Font RL, Naumann GO. Herpes simplex
stromal and endothelial keratitis. Granulomatous cell reactions at the level of Descemet’s membrane, the stroma,
and Bowman’s layer. Ophthalmology. 1990;97(6):722-8.
22. Leger F, Vital C, Negrier ML, et al. Histologic findings in a series of 1,540 corneal allografts. Ann Pathol.
2001;21(1):6-14.
23. Pepose JS. Herpes simplex keratitis: role of viral
infection versus immune response. Surv Ophthalmol.
1991;35(5):345-52.
24. Collum LM, Logan P, Ravenscroft T. Acyclovir
(Zovirax) in herpetic disciform keratitis. Br J Ophthalmol.
1983;67(2):115-8.
25. Barron BA, Gee L, Hauck WW, et al. Herpetic
Eye Disease Study. A controlled trial of oral acyclovir
for herpes simplex stromal keratitis. Ophthalmology.
1994;101(12):1871-82.
26. Wilhelmus KR, Mitchell BM, Dawson CR, et al.
Herpetic Eye Disease Study Group. Slitlamp biomicroscopy and photographic image analysis of herpes
simplex virus stromal keratitis. Arch Ophthalmol. 2009
Feb;127(2):161-6.
27. Wilhelmus KR, Sugar J, Hyndiuk RA, Stulting RD.
Corneal thickness changes during herpes simplex virus
disciform keratitis. Cornea. 2004 Mar;23(2):154-7.
28. Porter SM, Patterson A, Kho P. A comparison of local
and systemic acyclovir in the management of herpetic disciform keratitis. Br J Ophthalmol. 1990;74(5):283-5.
29. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye
Disease Study. A controlled trial of topical corticosteroids
for herpes simplex stromal keratitis. Ophthalmology.
1994;101(12):1883-95.
30. Tabbara KF, Al Balushi N. Topical ganciclovir in the
treatment of acute herpetic keratitis. Clin Ophthalmol.
2010 Aug 19;4:905-12.
31. Colin J. Ganciclovir ophthalmic gel, 0.15%: a valuable
tool for treating ocular herpes. Clin Ophthalmol. 2007
Dec;1(4):441-53.
32. Croxtall JD. Ganciclovir ophthalmic gel 0.15%: in
acute herpetic keratitis (dendritic ulcers). Drugs. 2011 Mar
26;71(5):603-10. doi: 10.2165/11207240-00000000000000.
33. Power WJ, Hillery MP, Benedict-Smith A, et
al. Acyclovir ointment plus topical betamethasone
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or placebo in first episode disciform keratitis. Br J
Ophthalmol. 1992;76(12):711-3.
34. Wilhelmus KR. Diagnosis and management of herpes
simplex stromal keratitis. Cornea. 1987;6(4):286-91.
35. Silverstein BE, Chandler D, Neger R, et al. Disciform
keratitis: a case of herpes zoster sine herpete. Am J
Ophthalmol. 1997;123(2):254-5.
FUNGAL KERATITIS
Signs and Symptoms
Fungal keratitis—also known as keratomycosis—represents a focal infection
of the cornea caused by fungal organisms. While there is no distinct racial
predilection for this condition, men do
appear to be affected at least twice as
often as women, and those in the middle decades of life (16-49 years) have
the highest incidence with regard to
age.1-3 The most common predisposing
factor is corneal trauma, usually from
organic vegetative matter such as a tree
branch.1,2,4 Other significant risk factors
include prior corneal surgery, prolonged
use of topical and oral corticosteroids
or other immunosuppressive agents,
systemic diseases (such as diabetes) and
contact lens wear.1,3 Fungal infections
tend to be more common in agricultural
and tropical environments.3
Patients typically report moderate to
severe unilateral pain with associated
vision loss. Clinically, fungal keratitis
has a well-known, classic pattern of
presentation. The infection begins
slowly and insidiously, producing a
feathery, branching pattern at the level
of the epithelium with a propensity for
forming ring infiltrates with satellite
lesions.4,5 The cornea often takes on a
dull gray appearance with heaping of
the epithelium. The epithelium often
acquires a dry, rough texture. In most
cases, this characteristic corneal appearance disappears over time and the fungal ulcer begins to resemble advanced
bacterial keratitis. Misdiagnosis at this
point occurs frequently if the history has
not been adequately elucidated. Fungal
keratitis is most often accompanied by a
26A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 26
severe anterior uveitis exhibiting a plasmoid aqueous with hypopyon.
Pathophysiology
Fungi can be broadly divided into
two groups. The first group consists
of molds, which are filamentous in
nature and grow in elongated, multicellular clusters called hyphae. Branching
hyphae intermingle to form fungal colonies. Molds can be further subdivided
into septate and non-septate fungi; this
distinction refers to the structure of the
hyphae. Less well-developed molds
contain simple, cylindrical filaments,
while higher order molds contain
thicker-walled cells with distinct junctions (or septa) between them. These
septa allow for a tougher, more durable
structure that is substantially resistant to
attack, while allowing neighboring cells
the capacity to communicate. Septate
fungi represent the most common
causes of fungal keratitis.4 The second
group of fungi consists of the yeasts.
Unlike filamentous molds, yeasts exist
as unicellar organisms. By definition,
yeasts do not form hyphae, but they can
form pseudohyphae, which are essentially chains of cells formed by incomplete budding. Considering all fungal
pathogens, the vast majority of keratitis
is associated with Fusarium, Aspergillus
(both septate filamentary fungi) and
Candida (a yeast).4,6,7
In order for fungal keratitis to develop, there must first be a breach in the
epithelial integrity. Fungi are opportunistic organisms; they cannot penetrate
an intact cornea and they do not enter
from limbal blood vessels.8 Hence, the
vast majority of cases can be traced
to some form of antecedent corneal
trauma, whether overt like a fingernail
scratch, or subtle, like a patient might
experience from overworn contact lenses. Immunosuppression from disease or
topical corticosteroids can further exacerbate the situation. Once within the
epithelium, fungal pathogens can gain
access to the stroma, where growth is
uninhibited in the absence of leukocyte
recruitment.9,10 Here, they proliferate
and give rise to hyphae colonies, in the
case of filamentous fungi or by simple
budding in the case of yeast fungi. Thus
begins a cycle of corneal destruction
by fungal expansion, inflammatory cell
infiltration and degradative cytokine liberation. Over time and without appropriate therapy, some pathogens may
even penetrate the corneal endothelium,
leading to fungal endophthalmitis.9
Management
Diagnosis of fungal keratitis begins
with clinical suspicion. Physicians should
have heightened suspicion in cases that
involve wispy or feathery-appearing
corneal ulcers, cases with a central lesion
and multiple satellite lesions or cases
presenting with a ring infiltrate, particularly if the history is positive for corneal
trauma or contact lens wear. Also, failure of a presumed bacterial keratitis to
respond to seemingly appropriate topical antibiotic therapy after several days
should lead the clinician to suspect a
possible fungal etiology.
Historically, confirmatory testing for
fungal keratitis involved performing corneal scrapings for smears (using Gram,
Giemsa, potassium hydroxide and calcofluor white stains) and cultures.11,12
Sabouraud’s media and blood agar are
the preferred media for facilitating
fungal growth. Unfortunately, the use
of stains on corneal scrapings typically
has a sensitivity of only about 50% in
fungal keratitis. Cultures may produce
confirmatory results within 72 hours,
however, cultures in up to 25% of cases
become positive only after two weeks
of incubation.4,11 Hence, there has
been a need to develop more effective
diagnostic tests. One method that has
demonstrated success on a small scale is
polymerase chain reaction (PCR).12 The
advantage of PCR is that it requires
only a small sample of corneal tissue
JUNE 15, 2012
6/4/12 2:30 PM
Fungal keratitis secondary to Fusarium infection.
the clock. Adjunctive oral therapy with
ketoconazole or fluconazole should be
considered for patients with deep stromal infection. Antifungal medications
are usually maintained for approximately 12 weeks with close monitoring
of the patient.
For those cases of fungal keratitis that
do not respond to aggressive drug therapy, surgical intervention must be considered.4 In a small 2005 study, adjunctive
therapy with phototherapeutic keratectomy (PTK) seemed to show promise, but
no large scale studies investigating PTK
for fungal keratitis have been published
since that time.21 Collagen cross-linking
therapy using riboflavin and UV-A light
has also been suggested as an adjunctive
treatment for a variety of corneal disorders, including fungal keratitis. While
no human studies have been published
to date, the results of in vitro and in
vivo animal studies are favorable.22,23
Ultimately, if the keratitis progresses to
the point of impending corneal perforation or extracorneal infection despite
maximum medical therapy, lamellar or
penetrating keratoplasty is indicated.
Unfortunately, even after corneal transplant surgery, fungal keratitis may recur.
A review of nearly 900 patients undergoing lamellar or penetrating keratoplasty
found the recurrence rate to be just over
6%.24 Risk factors for recurrence included
preoperative steroid use and more severe
infection prior to surgery.
Clinical Pearls
• While a significant risk factor for
fungal keratitis, injury by organic vegetative matter is by no means a guarantee
that the patient will develop the disease.
Fungal keratitis is quite uncommon,
particularly in temperate climates.4 For
this reason, it is not appropriate to use
antifungal medications on a prophylactic basis.
• As a rule, fungal keratitis is a slow,
insidious process. Acute and severe
corneal infections appearing overnight
should prompt the clinician to consider
a bacterial etiology, such as Pseudomonas
or Neisseria.
• Although topical natamycin is
commercially available, it is usually not
readily available. When prescribing,
anticipate that the commercial pharmacist will need to order this agent from
the manufacturer and advise the patient
accordingly. If antifungal medication is
required immediately due to the risk of
perforation or penetration, the services
of a compounding pharmacist will be
necessary; or, an immediate referral to
a corneal specialty center that may have
the resources to have the medications in
stock is indicated.
1. Garg P. Fungal, Mycobacterial, and Nocardia infections
and the eye: an update. Eye (Lond). 2012;26(2):245-51.
2. Gopinathan U, Sharma S, Garg P, Rao GN. Review of
epidemiological features, microbiological diagnosis and
treatment outcome of microbial keratitis: experience of over
a decade. Indian J Ophthalmol. 2009;57(4):273-9.
3. Gopinathan U, Garg P, Fernandes M, et al. The epidemiological features and laboratory results of fungal keratitis:
a 10-year review at a referral eye care center in South
India. Cornea. 2002;21(6):555-9.
4. Chang HY, Chodosh J. Diagnostic and therapeutic
considerations in fungal keratitis. Int Ophthalmol Clin. 2011
Fall;51(4):33-42.
5. Tuli SS. Fungal keratitis. Clin Ophthalmol. 2012;5:275-9.
6. Chowdhary A, Singh K. Spectrum of fungal keratitis in
North India. Cornea. 2005;24(1):8-15.
7. Doczi I, Gyetvai T, Kredics L, et al. Involvement of
Fusarium spp. in fungal keratitis. Clin Microbiol Infect.
2004;10(9):773-6.
8. Tamcelik N, Ozdamar A, Kizilkaya M, et al. Fungal
keratitis after nonpenetrating glaucoma surgery. Cornea.
2002;21(5):532-4.
9. Leal SM Jr, Pearlman E. The role of cytokines and
pathogen recognition molecules in fungal keratitis - Insights
from human disease and animal models. Cytokine. 2012.
[Epub ahead of print].
10. Sun Y, Chandra J, Mukherjee P, et al. A murine model
of contact lens-associated Fusarium keratitis. Invest
Ophthalmol Vis Sci. 2010;51(3):1511-6.
11. Sharma S, Kunimoto DY, Gopinathan U, et al.
Evaluation of corneal scraping smear examination methods in the diagnosis of bacterial and fungal keratitis: a
survey of eight years of laboratory experience. Cornea.
2002;21(7):643-7.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 27
CORNEA
and both viable and nonviable organisms can be detected.4 The downside of
this test is that it has a high tendency
toward false positives, is not yet widely
available and is quite expensive. In recent
years, confocal microscopy has emerged
as an efficient and reliable method of
identifying fungal keratitis in vivo.13,14
This technique allows for high resolution
visualization of the corneal cellular anatomy and is capable of imaging specific
pathogens and inflammatory elements.
Treating fungal keratitis can be quite
difficult. Most antifungal medications
are merely fungistatic, requiring both an
intact immune system and a prolonged
therapeutic course in order to be effective. Drug classes used to treat fungal
keratitis include the polyene antibiotics
(nystatin, amphotericin B and natamycin), pyrimidine analogs (flucytosine),
imidazoles (clortrimazole, miconozole,
econazole and ketoconazole), triazoles
(fluconazole, itraconazole voriconazole
and posaconazole), echinocandins,
(caspofungin and micafungin) and nonspecific antiseptics, such as chlorhexidine gluconate and silver sulfadiazine.
Natamycin is only available as a topical
formulation, while the other medications
have various routes of administration.15
Corticosteroids are generally avoided in
fungal keratitis as they can exacerbate
the disease.
Once diagnosed as fungal keratitis,
the treatment of first choice is typically
Natacyn (5% natamycin ophthalmic
suspension, Alcon), primarily because
of its commercial availability.16,17
Common alternatives for filamentary
fungal pathogens such as Aspergillus or
Fusarium include 0.15% amphotericin
B, 1% itraconazole, 2% econazole, and
more recently 1% voriconazole.16-19
For yeast infections of the cornea (e.g.,
Candida), 0.15% amphoteracin B is the
preferred therapy; alternatives include
0.2% fluconazole and 1% miconazole.20
All of the aforementioned topical
therapies are indicated hourly around
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6/1/12 3:17 PM
12. Vengayil S, Panda A, Satpathy G, et al. Polymerase
chain reaction-guided diagnosis of mycotic keratitis: a
prospective evaluation of its efficacy and limitations. Invest
Ophthalmol Vis Sci. 2009;50(1):152-6.
13. Brasnu E, Bourcier T, Dupas B, et al. In vivo confocal microscopy in fungal keratitis. Br J Ophthalmol.
2007;91(5):588-91.
14. Avunduk AM, Beuerman RW, Varnell ED, Kaufman
HE. Confocal microscopy of Aspergillus fumigatus keratitis. Br J Ophthalmol. 2003;87(4):409-10.
15. Thomas PA. Fungal infections of the cornea. Eye
(Lond). 2003 Nov;17(8):852-62.
16. Kalavathy CM, Parmar P, Kaliamurthy J, et al.
Comparison of topical itraconazole 1% with topical natamycin 5% for the treatment of filamentous fungal keratitis.
Cornea. 2005;24(4):449-52.
17. Loh AR, Hong K, Lee S, et al. Practice patterns
in the management of fungal corneal ulcers. Cornea.
2009;28(8):856-9.
18. Prajna NV, Nirmalan PK, Mahalakshmi R, et al.
Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis. Cornea.
2004;23(8):793-6.
19. Al-Badriyeh D, Neoh CF, Stewart K, Kong DC. Clinical
utility of voriconazole eye drops in ophthalmic fungal keratitis. Clin Ophthalmol. 2010;4:391-405.
20. Abdel-Rhaman MS, Soliman W, Habib F, Fathalla D.
A new long-acting liposomal topical antifungal formula:
human clinical study. Cornea. 2012;31(2):126-9.
21. Lin CP, Chang CW, Su CY. Phototherapeutic keratectomy in treating keratomycosis. Cornea. 2005;24(3):262-8.
22. Sauer A, Letscher-Bru V, Speeg-Schatz C, et al.
In vitro efficacy of antifungal treatment using riboflavin/
UV-A (365 nm) combination and amphotericin B. Invest
Ophthalmol Vis Sci. 2010;51(8):3950-3.
23. Galperin G, Berra M, Tau J, et al. Treatment of fungal
keratitis from fusarium infection by corneal cross-linking.
Cornea. 2012;31(2):176-80.
24. Shi W, Wang T, Xie L, et al. Risk factors, clinical features, and outcomes of recurrent fungal keratitis after corneal transplantation. Ophthalmology. 2010;117(5):890-6.
LATTICE CORNEAL DYSTROPHY
Signs and Symptoms
Lattice dystrophy (sometimes referred
to as Biber-Haab-Dimmer dystrophy) is
typically seen as a bilateral condition that
affects the central regions of the cornea
while generally sparing the periphery.1,2
Patients may be diagnosed on routine
examination in their teens or twenties,
although the condition may not become
symptomatic until the third or fourth
decade of life.2,3 Because of its autosomal
dominant inheritance pattern, patients
with lattice dystrophy characteristically
have a parent and/or a sibling with a
similar history and findings.1-3
Clinically, lattice corneal dystrophy
can be viewed as a series of translu28A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 28
Lattice dystrophy as seen with
retroillumination of the cornea.
cent, linear, radially-oriented, branching opacities that somewhat resemble
cracked glass. Located in the anterior
stroma, the deposits are best viewed
with retroillumination on biomicroscopy or direct ophthalmoscopy. In the
early stages, vision may be unaffected
or only mildly reduced; however, as the
lattice lines and other deposits coalesce,
a corneal haze develops, and visual acuity may drop off precipitously. It is not
unusual to see older patients with this
condition manifesting vision of 20/80
or worse. Patients may also report varying degrees of ocular irritation, ranging
from a mild foreign body sensation to
pronounced pain. This is complicated
by the fact that corneal sensitivity may
be diminished in lattice dystrophy.1 The
most significant complication, aside
from reduced vision, is the propensity
toward recurrent epithelial erosions—a
consequence that is seen in several of
the stromal dystrophies.
Pathophysiology
Corneal dystrophies are non-infectious, non-inflammatory, hereditary
disorders that involve abnormal deposition or retention of material within the
cornea. They are usually due to faulty
cellular metabolism. The underlying
etiology is often related to a specific
genetic mutation.4 Corneal dystrophies
are categorized by the layer of the cornea in which they are found, including
the superficial anterior layers (epithelium and epithelial basement membrane),
Bowman’s layer, the corneal stroma, or
the endothelium.
In lattice dystrophy (as with granular,
Avellino and Reis-Bückler), the mutation appears to be in the Transforming
Growth Factor Beta 1 gene (TGFβ-1),
also known as the BIGH3 gene.1,2,5
This mutation leads to production of an
abnormal adhesion protein in the cornea
(keratoepithelin), which in turn results in
accumulation of insoluble proteins. The
deposits in lattice dystrophy are composed of amyloid, a protein associated
with a number of other degenerative
conditions including Alzheimer’s disease,
Parkinson’s disease, rheumatoid arthritis,
atherosclerosis and bovine spongiform
encephalopathy (“mad-cow disease”).6
Amyloid can be seen on histopathologic
evaluation as amorphous pink deposits
with hematoxylin and eosin stains; amyloid deposits also stain positively with
Congo red dye.2,7
In the cornea, the amyloid deposits
of lattice dystrophy assume a linear and
dendritic pattern, accumulating within
and radiating outward from the visual
axis at the level of the anterior stroma.
This aggregation of material and the
resultant disruption of the normal architecture of the stromal collagen fibrils
results in diminished transparency,
stromal haze, scarring and ultimately
visual deterioration. Additionally, amyloid deposits often occur between the
epithelium and Bowman’s membrane,
resulting in irregular epithelial basement
membrane complexes.8 These abnormalities interfere with normal epithelial
adhesion, creating a propensity toward
recurrent corneal erosion syndrome.
Management
Unfortunately, there is no universally
accepted restorative process for individuals with lattice corneal dystrophy.
Patients typically endure the situation
as long as possible, relying on a variety of lubricants for palliative relief of
ocular irritation. The most significant
event associated with lattice dystrophy
JUNE 15, 2012
6/1/12 4:30 PM
Characteristic refractile corneal deposits in lattice dystrophy.
visual acuity over a two- to four-month
period. The authors suggested that this
procedure, which unlike PTK does not
involve stromal ablation, might provide
a viable, repeatable option for less severe
cases of lattice corneal dystrophy.13
Clinical Pearls
• There are actually three recognized types of lattice corneal dystrophy.
Type I, which is the most common
form seen clinically, is described above.
Type II, also known as Meretoja or
Finnish, involves concurrent systemic
manifestations such as nerve palsies,
skin disorders, and facial abnormalities;
decreased corneal sensation and open
angle glaucoma are common associations.1-3,7,8 Type III lattice dystrophy
is autosomal recessive with a late adult
onset, usually in the sixth decade of
life. First described in 1987, it may be
unilateral or bilateral, and presents with
coarse lattice lines that stretch from
limbus to limbus.14
• The most common corneal dystrophies encountered in clinical practice
include lattice dystrophy, granular
dystrophy, epithelial basement membrane dystrophy (EBMD) and Fuch’s
endothelial dystrophy. These conditions
are distinguished based upon: 1) the
involved layer of the cornea, and 2) the
clinical and histological appearance of
the lesions.
• Since the majority of lattice cornea
dystrophy is autosomal dominant, it is
important to examine family members
(especially siblings or children) for similar ocular findings.
• The use of oral doxycycline has
been advocated in the management of
recalcitrant recurrent corneal erosions.15
Doxycycline serves to inhibit the production of matrix metalloproteinases, which
are important mediators in the process
of corneal inflammation. Despite this
premise, there is no direct evidence that
the use of cycline medications promotes
resolution of recurrent erosions in cases
of lattice corneal dystrophy.
1. Klintworth GK. Corneal dystrophies. Orphanet J Rare
Dis. 2009 23;4:7.
2. Birkholz ES, Syed NA, Wagoner, MD. Corneal stromal
dystrophies: A clinicopathologic review. EyeRounds.
org. August 4, 2009. Available at: www.eyerounds.org/
cases/43-corneal-stromal-dystrophies.pdf. Accessed
December 26, 2011.
3. Cheung J, Sharma S. Ophthaproblem. Lattice corneal
dystrophy. Can Fam Physician. 2001;47:265, 271.
4. Vincent AL, Patel DV, McGhee CN. Inherited corneal
disease: The evolving molecular, genetic and imaging
revolution. Clin Experiment Ophthalmol 2005;33(3):30316.
5. Patel DA, Chang SH, Harocopos GJ, et al. Granular
and lattice deposits in corneal dystrophy caused by
R124C mutation of TGFBIp. Cornea. 2010;29(11):121522.
6. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid
fibril protein nomenclature: 2010 recommendations from
the nomenclature committee of the International Society
of Amyloidosis. Amyloid. 2010;17(3-4):101-4.
7. Stix B, Leber M, Bingemer P, et al. Hereditary lattice
corneal dystrophy is associated with corneal amyloid
deposits enclosing C-terminal fragments of keratoepithelin. Invest Ophthalmol Vis Sci. 2005;46(4):1133-9.
8. Chronister CL, Wasilauski ME. Recurrent corneal erosion (RCE) secondary to lattice dystrophy in a patient
with acquired immune deficiency syndrome (AIDS).
Optometry. 2005;76(12):713-9.
9. Stewart OG, Pararajasegaram P, Cazabon J, Morrell
AJ. Visual and symptomatic outcome of excimer phototherapeutic keratectomy (PTK) for corneal dystrophies.
Eye (Lond). 2002;16(2):126-31.
10. Das S, Langenbucher A, Seitz B. Delayed healing of
corneal epithelium after phototherapeutic keratectomy for
lattice dystrophy. Cornea. 2005;24(3):283-7.
11. Szentmáry N, Seitz B, Langenbucher A, et al.
Histologic and ultrastructural changes in corneas with
granular and macular dystrophy after excimer laser phototherapeutic keratectomy. Cornea. 2006;25(3):257-63.
12. Jain S, Austin DJ. Phototherapeutic keratectomy for
treatment of recurrent corneal erosion. J Cataract Refract
Surg.1999;25(12):1610-4.
13. Hida T, Proia AD, Kigasawa K, et al. Histopathologic
and immunochemical features of lattice corneal dystrophy
type III. Am J Ophthalmol. 1987 Sep 15;104(3):249-54.
14. Morita Y, Chikama TI, Yamada N, et al. New mode
of treatment for lattice corneal dystrophy type I: corneal
epithelial debridement and fibronectin eye drops. Jpn J
Ophthalmol. 2011 Nov 12. [Epub ahead of print]
15. Dursun D, Kim MC, Solomon A, Pflugfelder SC.
Treatment of recalcitrant recurrent corneal erosions with
inhibitors of matrix metalloproteinase-9, doxycycline and
corticosteroids. Am J Ophthalmol. 2001;132(1):8-13.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 29
CORNEA
is recurrent corneal erosion; historically, this has been treated with artificial
tears, hyperosmotic agents (e.g., 5%
sodium chloride solution or ointment),
and bandaging with either a pressure
patch or soft contact lens. Prophylaxis
with a broad-spectrum topical antibiotic
(fourth-generation fluoroquinolone,
q.i.d.) is recommended during acute
stages, while topical non-steroidal antiinflammatory drops, q.i.d., may help
to ameliorate the discomfort associated with this event. Anterior stromal
puncture is not advisable for recurrent
erosions secondary to corneal dystrophy,
and should be employed only in those
cases of erosion associated with prior
ocular trauma.
In later stages involving significant
visual compromise or recalcitrant corneal erosions, PTK may be employed
as a means to restore some degree of
functional vision and also diminish the
recurrence of erosion.9 The excimer
laser ablates the more superficial opacities, helping to smooth the corneal surface and allow the new epithelial cells to
re-adhere more tightly to the underlying
Bowman’s membrane.10 In most cases
of corneal dystrophy, PTK is effective
in achieving symptomatic improvement; however, the greatest success has
been noted in granular and macular
dystrophies.10-12 Comparatively, PTK
may induce delayed epithelial wound
healing in cases of lattice dystrophy.10
In the most severe cases, a lamellar
or full-thickness keratoplasty may be
required to restore functionality to the
cornea, although lattice dystrophy has
been known to recur even after corneal
transplant surgery.1
Recently, a non-invasive, topical,
therapeutic approach to managing lattice dystrophy has been described. In
a small, non-randomized study,13 the
application of autologous fibronectic
eye drops to a freshly debrided cornea
was shown to restore a more regular
corneal surface and actually improve
29A
6/1/12 3:17 PM
THE ABCs OF CORNEAL SURGERY
Over the last 25 years, a multitude of new ophthalmic procedures
have been pioneered and perfected. Corneal surgery, once limited to
penetrating keratoplasty and reserved for only the most severe and
sight-threatening of disorders, has evolved to include a wide variety
of specialized procedures for both corrective and cosmetic purposes.
With such diversity and rapid change, it can be difficult for non-corneal
specialists to recognize the jargon and communicate effectively with
surgeons and patients. For this reason, we’ve included a glossary of the
more commonly discussed corneal surgeries.
• PK or PKP – Penetrating Keratoplasty.
o PK refers to full-thickness corneal transplant surgery. It is usually
performed in cases of extensive scarring, degeneration or perforation of the cornea. PK has been employed successfully in many
cases for nearly a century, but it has numerous shortcomings, the
most significant of which include the need for sutures, healing
time, visual instability and the potential for graft rejection.1 The
need for prolonged use of corticosteroids post-operatively also
puts the patient at risk for secondary glaucoma and cataracts.
• DLK – Deep Lamellar Keratoplasty. Sometimes referred to simply as
LK – Lamellar Keratoplasty.
o DLK is a very general term describing the surgical replacement of
a portion of the corneal depth by donor tissue, in contrast to PK,
which replaces the entire thickness of the cornea. In the literature, the term DLK has been used to refer either to anterior or
posterior lamellar keratoplasty.
• DALK– Deep Anterior Lamellar Keratoplasty.
o DALK is a surgical procedure that serves to transplant the anterior cornea down to the level of Descemet’s membrane. The
surgeon employs a trephine and scalpel to remove the corneal
stroma after dissecting it away from the deeper structures. DALK
is most useful for the treatment of corneal disease in the setting
of a normally functioning endothelium; it offers an alternative
to PK, lessening the risk of graft rejection, irregular astigmatism
and corneal opacification. On the other hand, DALK carries the
potential danger of decreased visual acuity due to possible opacification at the interface layers.
o Indications: Common indications for DALK include keratoconus
and corneal scarring. Keratoconus patients are typically good candidates for DALK because of their young age and healthy endothelium. Less common indications for DALK include vernal keratoconjunctivitis, corneal dystrophies and ocular surface diseases with
limbal stem cell deficiency, including Stevens-Johnson syndrome,
ocular cicatricial pemphigoid and chemical or thermal burns.2
• PLK – Posterior Lamellar Keratoplasty.
o PLK is a surgical procedure that serves to transplant only the
most posterior elements of the cornea in an effort to replace
a dysfunctional endothelial layer. Earlier surgeries accomplished
this by creating an anterior flap of tissue, trephining the damaged
endothelium out and suturing the donor tissue in its place. PLK
instead preserves the preoperative corneal surface, achieving
transplantation of donor tissue via a large diameter scleral tunnel. A button of donor cornea consisting of posterior stroma,
Descemet’s membrane and endothelium is inserted via the
scleral tunnel into the anterior chamber, and positioned into
place with the aid of an air bubble. PLK has undergone several
iterations since it was first conceived by Dr. Jose Barraquer in the
1960s, and later developed and perfected by Dr. Gerrit Melles
in the 1990s.3
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001_ro0612_hndbk.indd 30
o Indications: The main indications for PLK (and its progeny listed
below) are diseases of the endothelium, such as Fuch’s dystrophy or
bullous keratopathy. Other conditions that may warrant this procedure
include some of the less common endothelial corneal dystrophies (e.g.,
posterior polymorphous dystrophy) or the iridocorneal endothelial
(ICE) syndromes. In order for these procedures to be successful, there
must be an absence of visually significant stromal scarring.
• DLEK – Deep Lamellar Endothelial Keratoplasty.
o DLEK was the name given to PLK when it was adopted in the
United States by Dr. Mark Terry in the early 2000s. Part of his
modification included reducing the surgical incision from 9mm to
a more manageable 5mm. The recipient cornea in this procedure
is dissected at the level of the posterior lamella and removed;
donor cornea is then prepared by cutting it to a depth of 150µm
via manual dissection. The button is then inserted into the anterior
chamber and positioned with the aid of an air bubble to form a
self-adhering interface with the exposed stromal bed of the recipient.4 In recent years, DLEK has generally given way to DSEK and
Descemet’s Membrane Endothelial Keratoplasty, which involve the
removal of far less corneal tissue from the recipient.
• DSEK – Descemet’s Stripping Endothelial Keratoplasty. Sometimes
referred to as DSAEK – Descemet’s Stripping Automated Endothelial
Keratoplasty
o Descemet’s stripping was first proposed in 2003, and reported
in 2005.5 Rather than dissecting the recipient cornea at the midstroma, this procedure peels away only Descemet’s membrane
and the endothelium (much in the same fashion that a capsulorhexis is performed on the anterior lens capsule during cataract
surgery). The donor button of posterior stroma, Descemet’s
membrane and endothelium is then implanted. DSEK has the
advantage of a smaller, potentially self-sealing incision, as well as
a smoother recipient interface for the donor tissue. Additionally,
DSEK has a more rapid rate of visual recovery, with full recovery
typically between one to six months post-operatively.
• DMEK – Descemet’s Membrane Endothelial Keratoplasty.
Sometimes referred to as DMAEK – Descemet’s Membrane
Automated Endothelial Keratoplasty.
o DMEK represents the most recent and least invasive approach
to endothelial keratoplasty. Like DSEK, DMEK involves an in vivo
stripping of Descemet’s membrane through a scleral incision.
However, rather than dissecting the donor cornea at the level of
the posterior stroma, only Descemet’s membrane and the endothelium are removed and transplanted. The DMEK procedure
combines the anatomical benefits of DSEK with enhanced visual
rehabilitation, typically to 20/40 or better in 90% of cases and
20/25 or better in 60% of cases within the first three months.6 As
one can imagine, DMEK is a painstakingly detailed and challenging
procedure, and is not yet widely performed by all surgeons.
1. Kang PC, Klintworth GK, Kim T, et al. Trends in the indications for penetrating keratoplasty, 1980-2001. Cornea. 2005;24(7):801-3.
2. Shimmura S, Tsubota K. Deep anterior lamellar keratoplasty. Curr Opin Ophthalmol.
2006;17(4):349-55.
3. Fernandez MM, Afshari NA. Endothelial Keratoplasty: From DLEK to DMEK. Middle East
Afr J Ophthalmol. 2010;17(1):5-8.
4. Terry MA. Deep lamellar endothelial keratoplasty (DLEK): pursuing the ideal goals of
endothelial replacement. Eye (Lond). 2003;17(8):982-8.
5. Price FW Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 50 eyes: A
refractive neutral corneal transplant. J Refract Surg. 2005;21(4):339-45.
6. Price MO, Giebel AW, Fairchild KM, Price FW Jr. Descemet’s membrane endothelial
keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial
survival. Ophthalmology. 2009;116(12):2361-8.
JUNE 15, 2012
6/1/12 3:17 PM
UVEA AND GLAUCOMA
Signs and Symptoms
While any person can experience
acute angle-closure glaucoma (AACG),
this condition is most common in
patients of Asian descent.1-6 Patients
are more likely to be older, hyperopic
and female.2-8 The etiology of angle
closure in young individuals differs from the older population and is
typically associated with structural and
developmental anomalies.9
Patients with acute AACG manifest
the signs and symptoms of ocular and
facial pain, unilateral blurring of vision,
photopsia in the form of colored haloes
around lights, and occasionally nausea
and vomiting. Acuity may be reduced
significantly in the involved eye, often
to 20/80 or worse.6,10,11 AACG is frequently unilateral, but may be bilateral
and, as a rule, should always be considered to have bilateral potential, though
the timing of the fellow eye involvement may be different.2,3
The hallmark signs of AACG
include significantly elevated intraocular pressure (IOP), virtually no visible
anterior chamber angle structures upon
gonioscopy, deep conjunctival and
episcleral injection in a circumlimbal
fashion, and a fixed, mid-dilated pupil.
Biomicroscopically, there typically will
be an edematous or “steamy” cornea
and shallow anterior chamber. There
may be a flat anterior chamber, or significant iris bombé, depending upon
the mechanism of the angle closure.
Applanation tonometry reveals
IOP in the range of 30mm Hg to
60mm Hg, occasionally higher in some
cases.12-14 Gonioscopy, which may
prove difficult because of microcystic
corneal edema, reveals no visible angle
structures without indentation. There
may be evidence of previous angle
closure episodes in the form of peripheral anterior synechiae (PAS) in the
Steamy corneal edema in acute angle closure
glaucoma.
involved or fellow eye.15,16
Medication history is important
in patients with AACG as the attack
may be medically induced. Of particular importance is the use of the
sulfa-based anti-epileptic medication
Topamax (topiramate, Ortho-McNeil
Pharmaceutical). Topiramate has been
associated with the development of
AACG (unilateral and bilateral) and
acquired myopia in patients previously
not at risk for angle closure.6,17-21
Pathophysiology
Anatomically, patients with AACG
have smaller eyes. It has been shown
that these patients have axial lengths
5% shorter, lenses that are 7% thicker,
anterior chambers that are 24% shallower, and anterior chambers with 37%
less volume than other age-matched
individuals.22 It has recently been
shown that eyes undergoing acute
angle closure have greater iris thickness
contributing to a shallower anterior
chamber.23,24 There is a high resistance to forward movement of aqueous
through the iris-lens channel due to a
tight apposition between the posterior
iris and anterior lens capsule. This resistance is known as relative pupil block.
It must be understood that pupil block
is a normal physiological phenomenon
occurring in virtually every phakic
person. In some cases, this resistance
becomes pathological and results in
AACG. In these individuals, there is an
increased pressure differential between
the anterior and posterior chambers
with resultant iris bombé and angle
closure. When this occurs, there is a
marked bowing forward (convexity) of
the iris, termed iris bombé.
Angle closure occurs when the
peripheral iris physically opposes the
trabecular meshwork or corneal endothelium and impedes aqueous outflow.
Several mechanisms are possible. This
may be simply due to genetic predisposition and anterior segment anatomy
(primary pupil block), or from sources
of secondary pupil block such as posterior synechiae, iris neovascularization,
aqueous misdirection syndrome, lenticular enlargement or displacement of
the lens or IOL.1,25
Another mechanism that may induce
angle closure involves an abnormal
configuration of the iris, the so-called
“plateau iris syndrome.” Patients with
this presentation may boast a deep
anterior chamber centrally; however,
the iris demonstrates an unusual laxity,
coming into close approximation with
the angle peripherally. These patients
may be prone to “angle crowding” and
subsequent closure during physiologic
or pharmacologic dilation.25
Expansion of the choroid appears
to be a significant contributory factor for AACG in some cases.21,26-28
Ultrasound biomicroscopy has clearly
demonstrated choroidal expansion as
well as shallow choroidal effusions
in patients undergoing angle closure
attacks. This is associated with anterior rotation of the ciliary body as well
as forward movement of the iris and
lens with subsequent shallowing of the
anterior chamber and closure of the
angle.6,21,26-29 Due to expansion of the
choroid and ciliary body edema (with
possible choroidal effusion), there is
a relaxation of the lens zonules with
increased laxity and thickening of the
lens. Along with the angle closure
glaucoma, there is refractive error shift
with several diopters of acquired myopia. The clinical picture of choroidal
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 31
UVEA AND GLAUCOMA
ACUTE ANGLE CLOSURE
GLAUCOMA
31A
6/1/12 3:18 PM
expansion-induced AACG differs from
that seen in primary pupil block in that
there is a flat anterior chamber without
iris bombé.
A number of conditions may lead
to choroidal expansion and secondary
angle closure in eyes not at anatomical
risk for angle closure, including scleritis,
Vogt-Koyanagi-Harada syndrome, pan
retinal photocoagulation, HIV infection
and cavernous sinus fistula.29 Choroidal
expansion-induced angle closure glaucoma has also been reported frequently
due to administration of sulfa-based
medications, such as sulfonamide, acetazolamide, topiramate and hydrochlorothiazide. Topiramate, which is used
to manage chronic headache as well as
induce weight loss, among other uses,
has been strongly implicated in choroidal expansion-induced bilateral angle
closure glaucoma along with induced
myopia.21,28 The theorized mechanism
may be an inflammatory sulfa-allergic
reaction.6
Management
The paramount concern in managing any pupil block angle-closure attack
is to alter the physiologic mechanisms
that cause the cornea to appose the
trabecular meshwork.1 In primary
pupil block, the tight apposition of
the posterior iris to the anterior lens
surface in the mid-dilated state must
be broken. This is done by lowering
the IOP so that the iris can function
normally and move from this middilated, pupil-blocking state. This must
be done quickly, as structural damage
to the nerve fiber layer and trabecular
meshwork and functional damage to
the visual field can occur within 48
hours.11,12,30
Choice of primary medication
depends upon the pressure at presentation. As most miotics are ineffective
at pressures over 40mm Hg due to iris
ischemia, aqueous suppressants such as
topical beta-blockers, alpha-2 adren32A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 32
ergic agonists and carbonic anhydrase
inhibitors should be used initially.30
Prostaglandin analogs also appear to
be an efficacious topical therapy for
patients with chronic angle closure
glaucoma. Though they will not cause
harm it is widely felt that the medications’ effects are too slow to be effective
in acute situations.33-37
Once the IOP is below 40mm
Hg, topical pilocarpine 1-2% can be
used to miose and reopen the angle.
Higher concentrations of pilocarpine
should be avoided as this can lead to
uveal congestion and actually worsen
the condition. Topical steroids, such
as prednisolone acetate 1% or difluprednate 0.5% emulsion, can be used
for the resultant inflammation. If the
patient does not achieve significant
reduction in IOP after 60 minutes, an
oral carbonic anhydrase inhibitor (acetazolamide 2 x 250mg tablets) can be
employed. A hyperosmotic agent, such
as three to five ounces of oral glycerin
over ice, may also assist in lowering the
IOP and breaking the attack. It is safe
to discontinue acute medical intervention when the IOP falls below 30mm
Hg and the angle structures are again
visible with gonioscopy. The patient
should be maintained on the following medications until surgical therapy
can be employed: pilocarpine 2% and
prednisolone acetate 1% q.i.d., as well
as a topical beta blocker and an alpha-2
adrenergic agonist b.i.d.
The quintessential treatment for
primary pupil block AACG is laser
peripheral iridotomy (LPI).6,8,11,16,3741 This should be performed as soon
as safely possible. LPI will allow the
aqueous fluid pressure to equilibrate
between the posterior and anterior
chamber. This will permit the iris
to relax backward with dissipation
of iris bombé allowing deepening of
the anterior chamber opening of the
angle, and aqueous access to trabecular
drainage again. LPI should also be
performed subsequently on any fellow
eyes that are potentially occludable.42
Adjunctively, laser peripheral iridoplasty—an irido-retraction procedure—can be performed to physically
pull the iris taught and away from the
trabecular meshwork. In fact, laser
peripheral iridoplasty has been shown
to be a safe, primary treatment for
AACG.8,38,39 Incisional ocular surgery in the form of trabeculectomy,
cataract extraction, cyclodestructive
procedures, glaucoma implant and
goniosynechialysis remain as options
for cases unresponsive to medical and
laser therapies.38,43-45 Trabeculectomy
and goniosynechialysis are often combined with cataract extraction.
In cases of AACG that are determined to be precipitated by a systemic
medication, therapy is different. Often,
discontinuation of the medication will
resolve the glaucoma. However, when
the choroid contributes to angle closure
glaucoma (which is often the mechanism of medicine-induced AACG),
the use of a potent cycloplegic agent
such as atropine, as well as topical steroids, will allow for ciliary body relaxation and posterior rotation with resolution of the angle closure.6,17,21,26,27,29
Aqueous suppressants can be used
concurrently, but miotics should be
avoided in these cases.
Following successful LPI, IOP may
still be elevated secondary to damage to
the trabecular meshwork caused by the
prolonged or repeated iris-meshwork
apposition.31 Persistent trabecular-iris
contact or peripheral anterior synechia
may block aqueous outflow resulting in a progressive process in which
Schlemm’s canal sustains endothelial
damage with subsequent canal occlusion. Trabecular cell damage may also
produce impairment of mitochondrial
function and subsequent fusion of the
trabecular beams.46 These changes may
be the reason for residual glaucoma
after laser iridotomy or cataract surgery.
JUNE 15, 2012
6/1/12 3:21 PM
Clinical Pearls
• The most important consideration
in handling an acute angle-closure
attack is accurate diagnosis and prompt
intervention. AACG must be differentiated from other acute open-angle
conditions such as uveitic glaucoma,
glaucomatocyclitic crisis and phacolytic
glaucoma. The mechanism of angle
closure, such as primary pupillary block,
plateau iris, secondary pupillary block or
choroidal expansion, must be delineated.
If the etiology is uncertain, or if an
inflammatory glaucoma may be present,
a miotic should not be used, as this will
only exacerbate the condition.
• In unilateral cases of suspected
acute angle closure, the cornea may be
too edematous to allow for gonioscopic
evaluation of the anterior chamber
angle. In such a case, gonioscopy should
be performed on the uninvolved fellow
eye. In the vast majority of cases, by
nature of symmetry, the fellow eye will
have an occludable angle.55 If the fellow eye demonstrates a non-occludable
angle, it is not likely that the patient
has a primary acute angle closure. In
the event both corneas are edematous,
topical glycerin can be applied with
a cotton-tipped applicator to provide
appropriate deturgescence.
• The presence of a patent peripheral iridotomy does not necessarily
ensure that a patient is safe to dilate.
Gonioscopy must still be performed
prior to pharmacologic dilation.56
• The ultimate goal in the management of AACG attack is not to
merely lower the IOP, but to assist in
resolving the apposition of the iris to
the trabecular meshwork. Reduction
of IOP is one means by which clinicians can alter this anatomic relationship.
• Often, following successful LPI
for AACG, the angle will be open,
but the IOP will be elevated and the
patient is said to have “mixed mechanism glaucoma.” The use of this term
is not accurate. Angle damage following AACG compromises the outflow
facility following appositional closure.
Thus, there is one mechanism for the
residual IOP elevation and the term
“mixed mechanism glaucoma” should
be avoided.
1. Wang N, Wu H, Fan Z. Primary angle closure glaucoma in Chinese and Western populations. Chin Med J
(Engl). 2002;115(11):1706-15.
2. Foster PJ. The epidemiology of primary angle closure
and associated glaucomatous optic neuropathy. Semin
Ophthalmol. 2002;17(2):50-8.
3. Xu L, Zhang L, Xia CR, et al. The prevalence and
its effective factors of primary angle-closure glaucoma
in defined populations of rural and urban in Beijing.
Zhonghua Yan Ke Za Zhi. 2005;41(1):8-14.
4. Wojciechowski R, Congdon N, Anninger W, et al.
Age, gender, biometry, refractive error, and the anterior
chamber angle among Alaskan Eskimos. Ophthalmology.
2003;110(2):365-75.
5. Congdon NG, Youlin Q, Quigley H, et al. Biometry
and primary angle-closure glaucoma among Chinese,
white, and black populations. Ophthalmology. 1997;
104(9):1489-95.
6. Congdon NG, Friedman DS. Angle-closure glaucoma:
impact, etiology, diagnosis, and treatment. Curr Opin
Ophthalmol. 2003;14(2):70-3.
7. Fuchs J, Holm K, Vilhelmsen K, et al. Hereditary high
hypermetropia in the Faroe Islands. Ophthalmic Genet.
2005;26(1):9-15.
8. Huang S, Yu M, Qiu C, et al. The management of secondary glaucoma in nanophthalmic patients. Yan Ke Xue
Bao. 2002;18(3):156-9.
9. Ritch R, Chang BM, Liebmann JM Angle closure in younger patients. Ophthalmology. 2003
Oct;110(10):1880-9.
10. Sowka JW. Pupil block glaucoma from traumatic
vitreous prolapse in a patient with posterior chamber lens
implantation. Optometry. 2002;73(11):685-93.
11. Wong JS, Chew PT, Alsagoff Z, et al. Clinical course
and outcome of primary acute angle-closure glaucoma in
Singapore. Singapore Med J. 1997;38(1):16-8.
12. Lai JS, Tham CC, Chan JC, et al. Scanning laser
polarimetry in patients with acute attack of primary angle
closure. Jpn J Ophthalmol. 2003;47(6):543-7.
13. Lam DS, Chua JK, Tham CC, et al. Efficacy and
safety of immediate anterior chamber paracentesis in the
treatment of acute primary angle-closure glaucoma: a
pilot study. Ophthalmology. 2002;109(1):64-70.
14. Aung T, Ang LP, Chan SP, et al. Acute primary
angle-closure: long-term intraocular pressure outcome in
Asian eyes. Am J Ophthalmol. 2001;131(1):7-12.
15. Choi JS, Kim YY. Relationship between the extent
of peripheral anterior synechiae and the severity of visual
field defects in primary angle-closure glaucoma. Korean
J Ophthalmol. 2004;18(2):100-5.
16. Lim LS, Aung T, Husain R, et al. Acute primary angle
closure: configuration of the drainage angle in the first
year after laser peripheral iridotomy. Ophthalmology.
2004;111(8):1470-4.
17. Bhattacharyya KB, Basu S. Acute myopia induced
by topiramate: report of a case and review of the literature. Neurol India. 2005;53(1):108-9.
18. Fraunfelder FW, Fraunfelder FT, Keates EU.
Topiramate-associated acute, bilateral, secondary angleclosure glaucoma. Ophthalmology. 2004;111(1):109-11.
19. Craig JE, Ong TJ, Louis DL, et al. Mechanism of
topiramate-induced acute-onset myopia and angle closure glaucoma. Am J Ophthalmol. 2004;137(1):193-5.
20. Banta JT, Hoffman K, Budenz DL, et al. Presumed
topiramate-induced bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001;132(1):112-4.
21. Chen TC, Chao CW, Sorkin JA. Topiramate
induced myopic shift and angle closure glaucoma. Br J
Ophthalmol 2003;87:648-9.
22. Friedman DS, Gazzard G, Foster P, et al.
Ultrasonographic biomicroscopy, Scheimpflug photography, and novel provocative tests in contralateral eyes of
Chinese patients initially seen with acute angle closure.
Arch Ophthalmol. 2003;121(5):633-42.
23. Wang BS, Narayanaswamy A, Amerasinghe N,
et al. Increased iris thickness and association with
primary angle closure glaucoma. Br J Ophthalmol.
2011;95(1):46-50.
24. Cronemberger S, Calixto N, de Andrade AO, Mérula
RV. New considerations on pupillary block mechanism.
Arq Bras Oftalmol. 2010;73(1):9-15.
25. Sellem E. Angle closure mechanisms of glaucoma. J
Fr Ophtalmol. 2004 Jun;27(6 Pt 2):693-6.
26. Waheeb S, Feldman F, Velos P, et al. Ultrasound
Biomicroscopic analysis of drug-induced bilateral angle
closure glaucoma associated with supraciliary choroidal
effusion. Can J Ophthalmol 2003; 38:299-302.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 33
UVEA AND GLAUCOMA
For this reason, long-term medical
therapy may be necessary. Aqueous
suppressants are a good choice and it
appears that prostaglandin analogs also
work especially well.31-34
The abrupt IOP elevation in AACG
rapidly causes structural alterations. It
has been shown with optical coherence
tomography that there is an increase
in retinal nerve fiber layer (RNFL)
thickness immediately after the acute
attack, with subsequent atrophy months
later.47-51 This can explain later-onset
visual field and RNFL damage. The
acute attack has been shown to cause
disc pallor, RNFL atrophy and visual
field loss, but not necessarily an increase
in focal disc damage.51,52
Primary phacoemulsification plus
intraocular lens implantation is a
viable initial option for eyes with
AACG, resulting in lowered IOP,
reduced the use of antiglaucoma
medications and improved vision in
patients. This is a safe and effective
method of IOP control and can be
considered a first treatment option in
managing patients with AACG and
coexisting cataract.53,54
33A
6/5/12 9:52 AM
27. Quigley HA, Friedman DS, Congdon NG. Possible
mechanisms of primary angle closure and malignant
glaucoma. J Glaucoma 2003;12:167-80.
28. Ikeda N, Ikeda T, Nagata, et al. Ciliochoroidal effusion
syndrome induced by sulfa derivatives. Arch Ophthalmol
2002;120:1775.
29. Sakai H, Morine-Shinjyo S, Shinzato M, et al.
Uveal effusion in primary angle-closure glaucoma.
Ophthalmology. 2005;112(3):413-9.
30. Aung T, Husain R, Gazzard G, et al. Changes in retinal nerve fiber layer thickness after acute primary angle
closure. Ophthalmology. 2004;111(8):1475-9.
31. Sihota R, Lakshmaiah NC, Walia KB, et al. The
trabecular meshwork in acute and chronic angle closure
glaucoma. Indian J Ophthalmol. 2001;49(4):255-9.
32. Hoh ST, Aung T, Chew PT. Medical management of angle closure glaucoma. Semin Ophthalmol.
2002;17(2):79-83.
33. Kook MS, Cho HS, Yang SJ, et al. Efficacy of latanoprost in patients with chronic angle-closure glaucoma
and no visible ciliary-body face: a preliminary study. J
Ocul Pharmacol Ther. 2005;21(1):75-84.
34. Aung T, Chan YH, Chew PT, et al. EXACT Study
Group. Degree of angle closure and the intraocular
pressure-lowering effect of latanoprost in subjects
with chronic angle-closure glaucoma. Ophthalmology.
2005;112(2):267-71.
35. Chew PT, Hung PT, Aung T. Efficacy of latanoprost
in reducing intraocular pressure in patients with primary
angle-closure glaucoma. Surv Ophthalmol. 2002;47
Suppl 1:S125-8.
36. Hung PT, Hsieh JW, Chen YF, et al. Efficacy
of latanoprost as an adjunct to medical therapy for
residual angle-closure glaucoma after iridectomy. J Ocul
Pharmacol Ther. 2000;16(1):43-7.
37. Saw SM, Gazzard G, Friedman DS. Interventions
for angle-closure glaucoma: an evidence-based update.
Ophthalmology. 2003;110(10):1869-78.
38. Renard JP, Giraud JM, Oubaaz A. Treatment
of acute angle-closure glaucoma. J Fr Ophtalmol.
2004;27(6 Pt 2):701-5.
39. Lai JS, Tham CC, Chua JK, et al. Laser peripheral
iridoplasty as initial treatment of acute attack of primary
angle-closure: a long-term follow-up study. J Glaucoma.
2002;11(6):484-7.
40. Alsagoff Z, Aung T, Ang LP, et al. Long-term clinical
course of primary angle-closure glaucoma in an Asian
population. Ophthalmology. 2000;107(12):2300-4.
41. Choong YF, Irfan S, Menage MJ. Acute angle closure
glaucoma: an evaluation of a protocol for acute treatment. Eye. 1999(Pt 5):613-6.
42. Stefanescu-Dima A. Preventive iridotomy--a prospective study. Oftalmologia. 2004;48(3):61-71.
43. Harasymowycz PJ, Papamatheakis DG, Ahmed I,
et al. Phacoemulsification and goniosynechialysis in the
management of unresponsive primary angle closure. J
Glaucoma. 2005;14(3):186-9.
44. Lai JS, Tham CC, Lam DS. Incisional surgery
for angle closure glaucoma. Semin Ophthalmol.
2002;17(2):92-9.
45. Wang JK, Lai PC. Unusual presentation of angleclosure glaucoma treated by phacoemulsification. J
Cataract Refract Surg. 2004;30(6):1371-3.
46. Hamanaka T, Kasahara K, Takemura T.
Histopathology of the trabecular meshwork and
Schlemm’s canal in primary angle-closure glaucoma.
Invest Ophthalmol Vis Sci. 2011;17;52(12):8849-61.
47. Mansoori T, Viswanath K, Balakrishna N.
Quantification of retinal nerve fiber layer thickness after
unilateral acute primary angle-closure in Asian Indian
34A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 34
eyes. J Glaucoma. 2011 Sep 22. [Epub ahead of print].
48. Tsai JC, Lin PW, Teng MC, Lai IC. Longitudinal
changes in retinal nerve fiber layer thickness after
acute primary angle closure measured with optical
coherence tomography. Invest Ophthalmol Vis Sci.
2007;48(4):1659-64.
49. Fang AW, Qu J, Li LP, Ji BL. Measurement of retinal
nerve fiber layer in primary acute angle-closure glaucoma by optical coherence tomography. J Glaucoma.
2007;16(2):178-84.
50. Liu X, Li M, Zhong Y, et al. The damage patterns of
retinal nerve fiber layer in acute and chronic intraocular
pressure elevation in primary angle closure glaucoma.
Yan Ke Xue Bao. 2011;26(3):154-60.
51. Sng CC, See JS, Ngo CS, et al. Changes in retinal
nerve fibre layer, optic nerve head morphology, and
visual field after acute primary angle closure. Eye (Lond).
2011;25(5):619-25. Epub 2011 Mar 25.
52. Chew SS, Vasudevan S, Patel HY, et al. Acute primary angle closure attack does not cause an increased
cup-to-disc ratio. Ophthalmology. 2011;118(2):254-9.
53. Moghimi S, Lin S. Role of phacoemulsification in angle closure glaucoma. Yan Ke Xue Bao.
2011;26(3):121-31.
54. Su WW, Chen PY, Hsiao CH, Chen HS. Primary
phacoemulsification and intraocular lens implantation for acute primary angle-closure. PLoS One.
2011;6(5):e20056. Epub 2011 May 24.
55. Sawada A, Sakuma T, Yamamoto T, et al.
Appositional angle closure in eyes with narrow angles:
comparison between the fellow eyes of acute angleclosure glaucoma and normotensive cases. J Glaucoma.
1997;6(5):288-92.
56. Tanasescu I, Grehn F. Acute angle-closure glaucoma
despite previous Nd:YAG laser iridotomy: a report on 13
cases. Ophthalmologe. 2003;100(10):832-5.
PARS PLANITIS
Signs and Symptoms
Pars planitis typically affects younger
patients, between five and 40 years of
age.1 Pars planitis seems to have an
association with Crohn’s disease and
multiple sclerosis.2-8 Patients are frequently asymptomatic, but may present
with modestly diminished vision that is
slowly progressive. Typically, they will
complain of floaters. Visual acuity tends
to be worse in children with pars planitis as compared to adults both at time of
diagnosis and at follow-up.9 Further, in
children, vitreous hemorrhage appears to
be a more common complication than
in adults.10,11 Visual acuity ranges from
20/20 to no perception of light, with a
mean range of 20/40-20/50.12,13 Pars
planitis is typically bilateral, with both
eyes affected in 85% of the cases accord-
ing to one report.12 This disease has a
good prognosis with a final mean visual
acuity ranging from 20/30 to 20/40 in
90% of cases.7,12,14
Vitritis is present in virtually all
patients with pars planitis.12 Vitritis
may cause subsequent vitreous degeneration with a resultant posterior vitreous detachment. There frequently will
be an accumulation of inflammatory
exudates. This accumulation may be
small (snowballs) or extensive (snowbanks) and may occur anywhere in the
fundus. However, these inflammatory
aggregates are typically regulated by
gravity to the inferior fundus. There
also is likely to be the presence of cataracts (especially posterior subcapsular),
secondary glaucoma, retinal neovascularization with vitreous hemorrhage and
tractional retinal detachment, exudative
retinal detachment, retinal vascular
sheathing, papillitis and cystoid macular edema (CME).7,10-12,14-19 While
vitreous snowballs and snowbanks are
frequently encountered, they are by
no means present in every eye with
pars planitis and need not be present
to make this diagnosis.12,18,20 CME
and cataract are the most frequently
encountered visual complications in
patients with pars planitis.12,17,18
A detailed family history (or examination) may disclose other family members with pars planitis. The genetic predisposition of pars planitis is unknown;
however, the frequent occurrence of
this condition in family members suggests that a common hereditary and/or
environmental factor contributes to the
disease.21-25
Pathophysiology
Pars planitis is a posterior/intermediate uveitis. It may be associated with
various systemic diseases or may be
idiopathic in nature.1 There are exacerbations and remissions and typically
this disorder runs a very long course.
Inflammatory mediators will increase
JUNE 15, 2012
6/1/12 3:22 PM
Pars planitis generally has a favorable outcome.6,7,12-14,17,28,29 Treatment
should be conservative and often
involves only periodic monitoring,
especially if vision is only minimally
disturbed by vitritis and CME.
If treatment is undertaken due
to vision loss from CME or vitreous clouding, then steroids form the
cornerstone of management.7,12,17,18,
30,31 Periocular, intravitreal, and sys-
Inferiorly located snowballs and snowbanks in pars planitis.
temic corticosteroids have all been
employed, as well as other immunosuppressive drugs. However, once a
commitment to use systemic steroids
is made, typically they are used for
months. With this treatment comes
the possible attendant complications of steroid-induced cataracts and
glaucoma.32 Topical steroids, such
as prednisolone and loteprednol, are
employed if there is a concomitant
anterior uveitis or CME. However, in
these cases, the anterior chamber reaction is not a true anterior uveitis, but
a spill-over from the posterior uveitis.
Topical non-steroidal anti-inflammatory drugs (NSAIDs) for CME
remain a consideration.
In severe or unresponsive cases,
transscleral cryoretinopexy or thermal laser photocoagulation can be
directed against the snowbanks to
destroy the inflamed areas along with
the infiltrates.15,32-35 These treatments
can reduce intraocular inflammation,
increase visual acuity, and decrease
dependence upon systemic steroids.
Vitrectomy can also be used to clear
the vitreous of both cells and hemorrhage.36,37 In that CME is a significant
cause of vision reduction in eyes with
pars planitis, intravitreal bevacizumab
has been seen as an effective therapy to
manage this complication.38-42
A recent report examined the successful use of twice-daily topical dif-
luprednate 0.05% emulsion (Durezol,
Alcon) in a child with pars planitis.
Although not a standard treatment,
it was speculated that topical difluprednate therapy could be a useful
short-term treatment option while
alternative treatments are considered
or immunosuppressive agents build to
therapeutic levels.43
Due to the strong association with
pars planitis, MRI testing for multiple
sclerosis is indicated as part of management. This is especially true for
females between the ages of 20 and 40
years.6,7
Clinical Pearls
• Posterior vitreous detachment
is rare in younger patients; however,
PVD is quite common in pars planitis.
Consider pars planitis when encountering PVD in younger patients.
• Always consider pars planitis in
cases of asymptomatic vitreous cells in
healthy, younger patients.
• When suspecting pars planitis,
carefully examine the inferior retina and
vitreous for snowballs and snowbanking.
• Children with pars planitis are
more likely than adults to experience
vitreous hemorrhage. Pars planitis
should be considered in the differential diagnosis of pediatric vitreous
hemorrhage.
• Pars planitis is the leading cause of
pediatric vitreous hemorrhage.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 35
UVEA AND GLAUCOMA
Management
Image courtesy of Dr. Catherine Derewyanko
vasopermeability of retinal capillaries
resulting in posterior segment inflammatory cells as well as CME.
The chronic inflammation in pars
planitis appears to consist of helper
T cells, both in the pars plana and
the retinal vasculature.24 Snowbanks
consist of posteriorly detached and
collapsed vitreous with cellular proliferation from the retina with nonpigmented ciliary epithelium. Electron
microscopy has demonstrated the presence of fibrous astrocytes and collagen.
Vitreous snowballs consist of granulomatous inflammation.19,26
Serologic evaluation of patients suggests an immunogenic predisposition
exists to pars planitis. Several studies
attempting to identify frequencies of
human leukocyte antigen (HLA) class
II alleles with pars planitis have shown
a strong association with the HLADR2 suballeles, -DR15, HLA-DR51
and HLA-DR17.8,14,24,27 A common
immunogenetic link between multiple
sclerosis and pars planitis may be associated with the HLA-DR15 allele.
This association may represent genetic
linkage to the HLA-DR locus or a
role for the HLA-DR15 gene product
in the pathogenesis of both of these
diseases.14 The strong association of
pars planitis with HLA-DR2 and the
temporal development of MS in some
patients with pars planitis further supports an association between pars planitis and MS.8
35A
6/1/12 3:23 PM
1. Maris K, Van Calster J, Wouters C, et al. Clinical
symptoms and complications of pars planitis in childhood. Bull Soc Belge Ophtalmol. 2005;(295):29-33.
2. Gorrono-Echebarria MB, Albarran F, et al.
Inflammatory bowel disease (Crohn’s disease) in a
Spanish patient with pars plana exudates: report of a
new case and review of the literature. Ocul Immunol
Inflamm. 2002;10(1):65-8.
3. Rosenbaum JT, Kurz D. An old crone finds a new
home: Crohn’s disease and pars planitis. Ocul Immunol
Inflamm. 2002;10(3):157-60.
4. Vidovic T, Cerovski B, Jukic T. The appereance
of pars planitis in multiple sclerosis. Coll Antropol.
2005;29(1):203-6.
5. Soheilian M, Heidari K, Yazdani S, et al. Patterns of
uveitis in a tertiary eye care center in Iran. Ocul Immunol
Inflamm. 2004;12(4):297-310.
6. Zein G, Berta A, Foster CS. Multiple sclerosis-associated uveitis. Ocul Immunol Inflamm. 2004;12(2):137-42.
7. Prieto JF, Dios E, Gutierrez JM, et al. Pars planitis:
epidemiology, treatment, and association with multiple
sclerosis. Ocul Immunol Inflamm. 2001;9(2):93-102.
8. Malinowski SM, Pulido JS, Goeken NE, et al. The
association of HLA-B8, B51, DR2, and multiple sclerosis in pars planitis. Ophthalmology. 1993;100(8):1199205.
9. Guest S, Funkhouser E, Lightman S. Pars planitis:
a comparison of childhood onset and adult onset disease. Clin Experiment Ophthalmol. 2001;29(2):81-4.
10. Phillips WB 2nd, Bergren RL, McNamara JA.
Pars planitis presenting with vitreous hemorrhage.
Ophthalmic Surg. 1993;24(9):630-1.
11. Lauer AK, Smith JR, Robertson JE, et al. Vitreous
hemorrhage is a common complication of pediatric pars
planitis. Ophthalmology. 2002;109(1):95-8.
12. Arellanes-Garcia L, Navarro-Lopez L, RecillasGispert C. Pars planitis in the Mexican Mestizo population: ocular findings, treatment, and visual outcome.
Ocul Immunol Inflamm. 2003;11(1):53-60.
13. Malinowski SM, Pulido JS, Folk JC. Long-term
visual outcome and complications associated with pars
planitis. Ophthalmology. 1993;100(6):818-24.
14. Raja SC, Jabs DA, Dunn JP, et al. Pars planitis: clinical features and class II HLA associations.
Ophthalmology. 1999;106(3):594-9.
15. Pollack AL, McDonald HR, Johnson RN, et al.
Peripheral retinoschisis and exudative retinal detachment in pars planitis. Retina. 2002;22(6):719-24.
16. Merayo-Lloves J, Power WJ, Rodriguez A, et
al. Secondary glaucoma in patients with uveitis.
Ophthalmologica. 1999;213(5):300-4.
17. Ortega-Larrocea G, Arellanes-Garcia L. Pars
planitis: epidemiology and clinical outcome in a large
community hospital in Mexico City. Int Ophthalmol.
1995;19(2):117-20.
18. Henderly DE, Genstler AJ, Rao NA, et al. Pars
planitis. Trans Ophthalmol Soc U K. 1986;105(Pt
2):227-32.
19. Green WR, Kincaid MC., et al. Pars planitis. Trans
Ophthalmol Soc UK. 1981;101(Pt 3)(3):361-7.
20. Henderly DE, Haymond RS, Rao NA, et al. The significance of the pars plana exudate in pars planitis. Am
J Ophthalmol. 1987;103(5):669-71.
21. Tejada P, Sanz A, Criado D. Pars planitis in a family. Int Ophthalmol. 1994;18(2):111-3.
22. Biswas J, Raghavendran SR, Vijaya R. Intermediate
uveitis of pars planitis type in identical twins. Report of a
case. Int Ophthalmol. 1998;22(5):275-7.
23. Duinkerke-Eerola KU, Pinckers A, Cruysberg JR.
Pars planitis in father and son. Ophthalmic Paediatr
36A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 36
Genet. 1990 Dec;11(4):305-8.
24. Wetzig RP, Chan CC, Nussenblatt RB, et al. Clinical
and immunopathological studies of pars planitis in a
family. Br J Ophthalmol. 1988;72(1):5-10.
25. Culbertson WW, Giles CL, West C, et al. Familial
pars planitis. Retina.1983;3(3):179-81.
26. Abu El-Asrar AM, Geboes K. An immunohistochemical study of the ‘snowbank’ in a case of pars
planitis. Ocul Immunol Inflamm. 2002;10(2):117-23.
27. Oruc S, Duffy BF, Mohanakumar T, et al. The
association of HLA class II with pars planitis. Am J
Ophthalmol. 2001;131(5):657-9.
28. Donaldson MJ, Pulido JS, Herman DC, et al. Pars
planitis: a 20-year study of incidence, clinical features,
and outcomes. Am J Ophthalmol. 2007;144(6):812-7.
29. Romero R, Peralta J, Sendagorta E, Abelairas J.
Pars planitis in children: epidemiologic, clinical, and
therapeutic characteristics. J Pediatr Ophthalmol
Strabismus. 2007;44(5):288-93.
30. Benitez Del Castillo Sanchez JM, Garcia Sanchez
J. Intravitreal injection of triamcinolone acetonide
in non infectious uveitis. Arch Soc Esp Oftalmol.
2001;76(11):661-4.
31. Duguid IG, Ford RL, Horgan SE, et al. Combined
orbital floor betamethasone and depot methylprednisolone in uveitis. Ocul Immunol Inflamm. 2005;13(1):1924.
32. Ermakova NA. Preference for transscleral cryocoagulation of peripheral exudate in intermediate uveitis
before traditional methods of treatment. Vestn Oftalmol.
2002;118(6):29-31.
33. Pulido JS, Mieler WF, Walton D. Results of peripheral laser photocoagulation in pars planitis. Trans Am
Ophthalmol Soc. 1998;96:127-37.
34. Verma L, Kumar A, Garg S, et al. Cryopexy in pars
planitis. Can J Ophthalmol. 1991;26(6):313-5.
35. Okinami S, Sunakawa M, Arai I, et al. Treatment
of pars planitis with cryotherapy. Ophthalmologica.
1991;202(4):180-6.
36. Potter MJ, Myckatyn SO, Maberley AL, et al.
Vitrectomy for pars planitis complicated by vitreous
hemorrhage: visual outcome and long-term follow-up.
Am J Ophthalmol. 2001;131(4):514-5.
37. Molina-Prat N, Adán AM, Mesquida M, et al.
Vitrectomy surgery for the treatment of the vitreoretinal complications of the pars planitis. Arch Soc Esp
Oftalmol. 2010;85(10):333-6.
38. Al-Dhibi H, Khan AO. Bilateral response following unilateral intravitreal bevacizumab injection in a
child with uveitic cystoid macular edema. J AAPOS.
2009;13(4):400-2.
39. Cervantes-Castañeda RA, Giuliari GP, Gallagher
MJ, et al. Intravitreal bevacizumab in refractory uveitic
macular edema: one-year follow-up. Eur J Ophthalmol.
2009;19(4):622-9.
40. Cordero Coma M, Sobrin L, et al. Intravitreal
bevacizumab for treatment of uveitic macular edema.
Ophthalmology. 2007;114(8):1574-9.
41. Karagiannis DA, Ladas ID. An unusual optic disc
neovascularization in a case of intermediate uveitis
associated with multiple sclerosis. Eur J Ophthalmol.
2008;18(6):1020-2.
42. Kurup S, Lew J, Byrnes G, et al. Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis
complicated by neovascularization. Acta Ophthalmol.
2009;87(3):349-52.
43. Kurz PA, Chheda LV, Kurz DE. Effects of
twice-daily topical difluprednate 0.05% emulsion in
a child with pars planitis. Ocul Immunol Inflamm.
2011;19(1):84-5.
STEROID-INDUCED GLAUCOMA
Signs and Symptoms
The patient with steroid-induced
glaucoma may be of any age, sex or race.
There may be a pre-existing personal
or family history of primary open angle
glaucoma.1 Invariably, there will be
a history of corticosteroid use. While
topical ophthalmic corticosteroids are
most likely to precipitate a rise in IOP,
other modalities of steroid use including intraocular and periocular injections, topical periocular dermatological
creams, inhaled steroids and oral steroid
use have been documented to have the
potential to cause a rise in IOP.2-13
Frequently, there will be a history of
long-term steroid use on the order of
weeks to months. Beyond the condition
for which the patient is using steroids,
there will be no visual or ocular symptoms of steroid-induced glaucoma,
unless the IOP elevation is profound
with resulting corneal edema and vision
blur. The rise in IOP may be modest
or may be dramatic. Topical steroids
such as betamethasone, dexamethasone,
prednisolone and difluprednate are
more likely to cause a rise in IOP than
steroids such as loteprednol or fluorometholone.3,14-17
Pathophysiology
Steroid-induced glaucoma presents
with an open anterior chamber angle
and increased IOP. The nature of the
raised pressure appears to be due to
outflow reduction. Beyond that, nothing more conclusive regarding the
pathophysiology of this condition can
be stated. One theory postulates that
steroids are responsible for the accumulation of glycoaminoglycans in the
trabecular meshwork.18 Once hydrated,
glycoaminoglycans cause an aqueous
outflow obstruction.18 Another thought
holds that steroids decrease the phagocytic ability of the trabecular meshwork
endothelial cells with a resultant increase
JUNE 15, 2012
6/1/12 3:23 PM
Management
Intuitively, management of patients
with steroid-induced glaucoma involves
discontinuation of the precipitating
medication, if possible. In cases where
the steroid has been injected, surgical
removal of the drug depot may be necessary.22 When steroid treatment has
not exceeded 12 months, discontinuation of the steroid will usually result in
a return to pre-treatment IOP levels.5
However, patients undergoing steroid
treatment over several continuous years
may develop a chronic IOP elevation
that is unalterable by steroid cessation.23
In patients where ocular steroid
cessation is not an option, management may include utilization of topical
steroids such as loteprednol, which is
known to reduce this complication.
If this is not successful or if changing
steroids is unacceptable, then the IOP
elevation can be treated with topical
aqueous suppressants. In that steroidinduced glaucoma appears to be due to
increased resistance to aqueous outflow
at the trabecular meshwork, therapies
designed to increase trabecular outflow,
such as laser trabeculoplasty and miotics, are of questionable benefit. One
study did, however, note a modest
effect of selective laser trabeculoplasty
in five of seven eyes with steroidinduced glaucoma and felt that this was
a reasonable temporizing procedure for
this condition.24 However, prostaglandin analogs appear to be successful in
the management of steroid-induced
glaucoma.25,26 However, their use may
be contraindicated by whatever ocular
inflammatory process necessitated the
need for steroids. Trabeculectomy,
stents and tube procedures remain an
option in patients who are uncontrolled
medically.27-30
Clinical Pearls
• Remember the realistic risks of steroid-induced glaucoma. While approximately 2/3 of the population are “steroid
responders,” only 5% of the population
will have a dramatic (>15mm Hg) rise
in IOP requiring glaucoma therapy.
• An elevation in IOP resulting
from steroid use typically takes four to
five weeks. Short-term steroid use is
unlikely to result in a significant glaucoma concern.
• Safe steroids that have a reputation
of lower propensity to cause IOP elevations must also be monitored carefully as
these agents can also cause a significant
IOP elevation.31,32
• While the incidence of IOP
response rate is similar to that of
prednisolone acetate, patients using
Durezol should be monitored closely
as the IOP response may occur sooner
(one to two weeks) and may be of a
greater magnitude.33
• Patients with primary open-angle
glaucoma are apt to demonstrate a rise
in IOP with steroid use.
• Children and infants are susceptible to steroid-induced pressure
elevations and should be monitored
carefully.34
1. Mitchell P, Cumming RG, Mackey DA. Inhaled
corticosteroids, family history, and risk of glaucoma.
Ophthalmology. 1999;106(12):2301-6.
2. Mohan R, Muralidharan AR. Steroid induced glaucoma and cataract. Indian J Ophthalmol.1989;37(1):13-6.
3. Kong L, Zhang C, Chen M, Xue G. Clinical analysis of
steroid glaucoma. Yan Ke Xue Bao. 1995;11(1):53-6.
4. Baratz KH, Hattenhauer MG. Indiscriminate use of
corticosteroid-containing eyedrops. Mayo Clin Proc.
1999;74(4):362-6.
5. Sapir-Pichhadze R, Blumenthal EZ. Steroid induced
glaucoma Harefuah. 2003;142(2):137-40, 157.
6. Singh IP, Ahmad SI, Yeh D, et al. Early rapid rise in
intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol. 2004;138(2):286-7.
7. Detry-Morel M, Escarmelle A, Hermans I. Refractory
ocular hypertension secondary to intravitreal injection
of triamcinolone acetonide. Bull Soc Belge Ophtalmol.
2004;(292):45-51.
8. Kaushik S, Gupta V, Gupta A, et al. Intractable glaucoma following intravitreal triamcinolone in central retinal
vein occlusion. Am J Ophthalmol. 2004;137(4):758-60.
9. Akduman L, Kolker AE, Black DL, et al. Treatment of
persistent glaucoma secondary to periocular corticosteroids. Am J Ophthalmol. 1996;122(2):275-7.
10. Garrott HM, Walland MJ. Glaucoma from
topical corticosteroids to the eyelids. Clin Experiment
Ophthalmol. 2004;32(2):224-6.
11. Schwartzenberg GW, Buys YM. Glaucoma secondary to topical use of steroid cream. Can J Ophthalmol.
1999;34(4):222-5.
12. Desnoeck M, Casteels I, Casteels K. Intraocular
pressure elevation in a child due to the use of inhalation steroids--a case report. Bull Soc Belge Ophtalmol.
2001;(280):97-100.
13. Caldwell JR, Furst DE. The efficacy and safety of
low-dose corticosteroids for rheumatoid arthritis. Semin
Arthritis Rheum. 1991;21(1):1-11.
14. Foster CS, Davanzo R, Flynn TE, et al. Durezol
(Difluprednate Ophthalmic Emulsion 0.05%) compared
with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol
Ther. 2010;26(5):475-83.
15. Korenfeld MS, Silverstein SM, Cooke DL, et al.
Difluprednate Ophthalmic Emulsion 0.05% (Durezol)
Study Group. Difluprednate ophthalmic emulsion 0.05%
for postoperative inflammation and pain. J Cataract
Refract Surg. 2009;35(1):26-34.
16. Smith S, Lorenz D, Peace J, et al. Difluprednate
ophthalmic emulsion 0.05% (Durezol) administered two
times daily for managing ocular inflammation and pain
following cataract surgery. Clin Ophthalmol. 2010;4:98391.
17. Ilyas H, Slonim CB, Braswell GR, et al. Long-term
safety of loteprednol etabonate 0.2% in the treatment
of seasonal and perennial allergic conjunctivitis. Eye
Contact Lens. 2004;30(1):10-3.
18. Sherwood M, Richardson TM. Evidence for in vivo
phagocytosis by trabecular endothelial cells. Invest
Ophthalmol 1958;59:216
19. Ohlmann A, Tamm ER. The role of myocilin in
the pathogenesis of primary open-angle glaucoma.
Ophthalmologe. 2002;99(9):672-7.
20. Tamm ER. Myocilin and glaucoma: facts and ideas.
Prog Retin Eye Res. 2002;21(4):395-428.
21. Lo WR, Rowlette LL, Caballero M, et al. Tissue
differential microarray analysis of dexamethasone induction reveals potential mechanisms of steroid glaucoma.
Invest Ophthalmol Vis Sci. 2003;44(2):473-85.
22. Okka M, Bozkurt B, Kerimoglu H, et al. Control
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 37
UVEA AND GLAUCOMA
in debris and concomitant decrease in
aqueous processing ability.
Recently, genetic mapping has led
to greater understanding of steroidinduced glaucoma. Steroids are believed
to induce the expression of a gene that is
located on chromosome 1 and is known
as TIGR or GLCIA. The resultant
genetic product is a glycoprotein called
myocilin.5 In the eye, myocilin is highly
expressed in the trabecular meshwork,
sclera, ciliary body and iris. In the trabecular meshwork, myocilin is found
within the cytoplasm of the cells and in
the juxtacanalicular region in association
with fibrillar extracellular matrix components. Recombinant myocilin increases
outflow resistance.19,20 In TM cells, the
expression of myocilin can be induced
via treatment with dexamethasone at a
time course similar to that observed in
steroid-induced glaucoma.18-21
37A
6/1/12 3:23 PM
Hyphema.
of steroid-induced glaucoma with surgical excision
of sub-Tenon triamcinolone acetonide deposits: a
clinical and biochemical approach. Can J Ophthalmol.
2010;45(6):621-6.
23. Espildora J, Vicuna P, Diaz E. Cortisone induced
glaucoma: A report on 44 affected eyes. J F Optalmol
1981; 4:503-8.
24. Rubin B, Taglienti A, Rothman RF, et al. The effect
of selective laser trabeculoplasty on intraocular pressure in patients with intravitreal steroid-induced elevated
intraocular pressure. J Glaucoma. 2008;17(4):287-92.
25. Ravinet E, Mermoud A, Brignoli R. Four years later:
a clinical update on latanoprost. Eur J Ophthalmol.
2003;13(2):162-75.
26. Scherer WJ, Hauber FA. Effect of latanoprost on
intraocular pressure in steroid-induced glaucoma. J
Glaucoma. 2000;9(2):179-82.
27. Honjo M, Tanihara H, Inatani M, Honda Y. External
trabeculotomy for the treatment of steroid-induced glaucoma. J Glaucoma. 2000;9(6):483-5.
28. Morales-Fernandez L, Martinez-De-La-Casa JM,
Garcia-Feijoo J, et al. Glaukos® trabecular stent used
to treat steroid-induced glaucoma. Eur J Ophthalmol.
2011 Oct 28:0. doi: 10.5301/ejo.5000073. [Epub ahead
of print].
29. Iwao K, Inatani M, Tanihara H; Japanese SteroidInduced Glaucoma Multicenter Study Group. Success
rates of trabeculotomy for steroid-induced glaucoma:
a comparative, multicenter, retrospective cohort study.
Am J Ophthalmol. 2011 Jun;151(6):1047-56.
30. Razeghinejad MR, Katz LJ. Steroid-Induced
Iatrogenic Glaucoma. Ophthalmic Res. 2011 Jul
13;47(2):66-80.
31. Rajpal RK, Digby D, D’Aversa G, et al. Intraocular
pressure elevations with loteprednol etabonate: a
retrospective chart review. J Ocul Pharmacol Ther.
2011;27(3):305-8.
32. Lu E, Fujimoto LT, Vejabul PA, Jew RL. Steroidinduced ocular hypertension with loteprednol etabonate
0.2%—a case report. Optometry. 2011;82(7):413-20.
33. Meehan K, Vollmer L, Sowka J. Intraocular pressure
elevation from topical difluprednate use. Optometry.
2010;81(12):658-62.
34. Hutcheson KA. Steroid-induced glaucoma in an
infant. J AAPOS. 2007;11(5):522-3.
HYPHEMA
Signs and Symptoms
Hyphema is defined as blood in
the anterior chamber (AC).1-23 The
condition where non-layered red blood
38A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 38
cells circulate in the anterior chamber
is referred to as microhyphema.2,15
Hyphema can occur as a result of blunt
or lacerating ocular or adnexal trauma;
following intraocular surgery; secondary
to conditions that induce iris neovascularization, such as diabetes, venous
occlusion or iris melanoma; secondary
to systemic conditions, such as juvenile
xanthogranuloma, myotonic dystrophy,
as a complication of keratouveitis (e.g.,
herpes zoster); as a complication of
other blood disorders, such as leukemia,
hemophilia, von Willebrand disease;
and in association with the use of substances that alter platelet or thrombin
function (e.g., ethanol, aspirin, warfarin).1-3 Complications of traumatic
hyphema include increased intraocular
pressure, peripheral anterior synechiae,
decreased visual acuity and corneal
dysfunction secondary to both blood
being in the anterior chamber and the
complication of corneal blood staining
and rebleeding with secondary hemorrhaging.1-3
Patients may present with the classic
signs of uveitis including conjunctival
hyperemia, blurred vision, throbbing
eye pain, photophobia, lacrimation,
blepharospam and blood in the anterior chamber.1-3 Any time that IOP is
elevated following blunt traumatic ocular injury, hyphema should be suspected
whether blood is visible in the anterior
chamber or not.
Since the underlying cause of most
hyphema is trauma, the epidemiologic
data regarding traumatic ocular injury
applies (mostly male, with injuries
occurring in or around the house, using
domestic tools or struck by a projectile).3-7 The most common concurrent
ocular injury associated with traumatic
hyphema is corneal injury, however,
adenexa echymosis and lacerations of
the eyelid are also common.3,4,6,7
The risk of secondary hemorrhage seems to be higher in AfricanAmericans than in whites.1,2,15
Secondary hemorrhage is generally
thought to convey a worse visual prognosis, although the outcome seems to
depend more on the size of the hyphema and the severity of the associated
ocular injuries.1,8
Hyphemas are classically graded by
the amount of visible blood occupying
the anterior chamber (AC). Less than
1/4 of the AC is grade 1; 1/4 to 1/2 is
grade 2, 1/2 to 3/4 is grade 3 and complete AC filling is grade 4. The term
“8-ball hemorrhage” connotes complete
filling of the anterior chamber with
blood. It is so named because when the
clotted blood fills the AC it makes the
anterior chamber appear black like a billiard “8-ball.”
Pathophysiology
There are two postulated mechanisms regarding traumatic hyphema
formation.1,2,15-17 Either direct, concussive forces cause mechanical tearing of
the fragile vasculature of the iris and/
or angle or concussive trauma creates
rapidly rising intravascular pressure
within these vessels, resulting in their
rupture.1,2,15-17 Blood in the AC is not,
by itself, necessarily harmful to the
ocular environment. However when
quantities are sufficient, macrophages
ingest the hemoglobin from the lysed
red blood cells. These hemoglobinladen macrophages obstruct the outflow
of aqueous humor by physically blocking access to the drainage area, resulting
in glaucoma.1-14,17 This is known as
hemolytic glaucoma.17 Hemosiderosic
glaucoma results when the trabecular
meshwork becomes obstructed by iron
from degraded red blood cells.9,17 It is
the rarest of the hypema-induced glaucomas.17 Ghost cell glaucoma results
from the trabecular meshwork being
obstructed by the denatured skeletons
of the disintegrating red blood cells.9,17
Finally, there is an inferred implication that any external force strong
enough to produce internal ocular
JUNE 15, 2012
6/1/12 3:37 PM
Management
A thorough ocular and systemic history is critical to managing hyphema.
Circumstances surrounding the event
and current medicines are important
pieces of data. Bleeding in the eye
warrants concern for systemic blood
disorders, such as antiphospholipid antibody disease (protein S and protein C),
hyperhomosysteinemia, dysfunction or
the clotting factors, sickle cell anemia,
hemophilia and Von Willebrand’s disease.1,2 If the patient is a poor historian
or questions arise regarding a patient’s
systemic status, testing for sickle cell
anemia (sickle prep or sickle dex), the
status of the commonly involved clotting
factors (factor V Leiden, antithrombin
III) and testing to rule out other disorders of clotting (prothrombin time [PT]
and activated partial thromboplastin
time [aPTT]) should be obtained.1,2
Ocular examination should include
evaluation of the adenexa. Imaging
should be ordered when appropriate to
rule out fracture or entrapment (X-ray,
CT scan). The cornea should be stained
to rule out abrasion, laceration or penetrating injury (Seidel sign or evidence
of iris prolapse). Signs indicating scleral
rupture (ruptured globe) include visual
acuity of 5/200 or worse (usually light
perception, if any vision is present),
subconjunctival hemorrhage of 270°
or more, IOP < 10mm Hg, shallowing of the anterior chamber or unusual
deepening of the anterior chamber,
generalized ocular/ adenexa chemosis
and inability to ophthalmoscopically
visualize structures of the posterior segment.22,23 The iris should be inspected
for iridodialysis. The lens should be
inspected for luxation. A dilated fundus
exam should be completed to rule out
vitreous hemorrhage and retina tears
or detachments. If a clear view of the
fundus is obstructed by the hyphema or
vitreous hemorrhage, B-scan ultrasonography should be completed.1,2
Controversy is ongoing whether
these individuals should be managed
as in- or out-patients.1-3,15 Most practitioners manage microhyphema and
uncomplicated grade I and II hyphema
without hospitalization. Cycloplegia
is accomplished using atropine 1 %,
b.i.d. to t.i.d. Lesser cycloplegics have
decreased working times, permitting iris
movement, which increases the risk of
clot movement and rebleeding.15 Local
inflammation is controlled via topical
prednisolone acetate 1 %, q2h to q.i.d.
or Durezol b.i.d. to q.i.d.15,24
If IOP is above 28mm Hg, becomes
increased through steroid response or is
judged to be too high for a fragile optic
nerve secondary to increased cupping
or a systemic disease state that reduces
perfusion, it can be controlled through
the use of a topical beta blocker b.i.d.
(respiratory function permitting) or
brimonidine b.i.d. to t.i.d.1,2,15 When
IOP requires acute attention (> 35mm
Hg), acetazolamide tablets, 500mg (2 x
250mg), b.i.d. can be prescribed (barring
contraindications) along with topical
aqueous suppressants, until the pressure is adequately controlled or until the
event resolves.
If corneal epithelial defects exist,
a topical antibiotic drop should be
employed. Patients should be instructed
to limit their activity to bathroom privileges and bed rest, laying with the head
elevated at an angle of 30° to help the
hyphema settle and avoid clot movement, which is a stimulus for rebleeding.15 Some type of eye shield should
used for additional protection.1-3,15
To further reduce the complication of
rebleeding only acetaminophen should
be used to manage pain.1
Immediate referral for surgical evacuation is indicated if there is corneal
blood staining, if IOP is > 60mm Hg,
if there is 8-ball hemorrhage or if the
IOP remains > 35mm Hg for seven
or more days.1-3 Follow-up should be
set no later than one week for uncomplicated cases and should be set for
consecutive days, as necessary in cases
where there are vision-threatening
issues.1,3
The use of oral antifibrinolytic
medications has been advocated by
some as the standard of care for cases of
hyphema.15,16 ACA-Amicar (aminocaproic acid, Xanodyne) and TA-Lysteda
(tranexamic acid, Ferring) tablets have
demonstrated superior properties for
stabilizing bleeding and maintaining
clot performance, reducing the risk for
rebleeding and injury worsening.15,16
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 39
UVEA AND GLAUCOMA
bleeding is also sufficiently strong to
produce direct damage to the adjacent
trabecular meshwork, resulting in sluggish aqueous drainage.18-21 When IOP
begins to rise with all of its potential
deleterious sequelae following a blunt
injury, the pathology is termed late or
chronic traumatic glaucoma.1,2,9,18-21
Clinically, the presence of increased
angle pigmentation, elevated IOP at
the time of the injury, hyphema, lens
luxation and the gonioscopic finding
of angle recession measuring more
than 180° were all associated with the
occurrence of chronic traumatic glaucoma.19 Researchers using ultrasound
biomicroscopy found that a wider angle
and the absence of cyclodialysis were
significant predictors for the subsequent
development of traumatic glaucoma.19
Finally, patients with the sickle
trait have a greater risk for elevated
IOP. Sickled red blood cells are not
as malleable as normal red blood cells.
Hyphema involving any sickled cells
further impedes the flow of aqueous
humor, slowing both aqueous and oxygen transfer. The hypoxic environment
encourages red blood cells encoded with
the sickle trait to undergo the sickle
transformation, which further obstructs
the trabecular meshwork.17 This is also
dangerous as only slightly elevated IOP
(>21mm Hg) can produce similar difficulties with perfusion at the nerve,
requiring management consideration.17
39A
6/1/12 3:23 PM
The surgical intervention of first
choice for hyphema with high
intractable intraocular pressure with
persistent corneal staining is anterior
chamber washout.10,16 Here, freefloating blood and obstructive clots
are removed via a single or double
paracentesis.10 Under the influence
of a topical anesthetic, a penetrating
incision can be made at the limbus
through which syringes can be placed
for the purpose of both introducing
sterile fluid into the AC, permitting
forced flow within the chamber and
for withdrawing aqueous and free
blood.10 A two-paracentesis procedure has been described where the
first is made in the lower temporal
quadrant to accommodate a 20-gauge
anterior chamber maintainer that
is connected to a bottle of balanced
salt solution and the second is made
in an upper quadrant to serve as the
evacuation site for liquefied blood
and clots.10 Proponents of the two
site technique approve of the well
maintained intraoperative IOP and
a stabilized AC depth with a minimized risk of re-bleeding owed to
the continuous positive intraoperative
maintenance of IOP.10
While intraocular pressures following paracentesis typically drop to
zero, measurements of IOP improve
to normal in as little as two hours
after the procedure, frequently
remaining at acceptable levels thereafter.7 The procedure is of particular
importance for patients with variations of sickle cell disease as using
IOP-lowering agents which induce
metabolic acidosis such as acetazolamide, methazolamide or manitol can
both induce crisis as well as worsen
resultant elevation in IOP and pathologic damage to the optic nerve.11
Trebeculectomy with anterior chamber washout has also been
examined as a solution for cases
involving pathologically elevated IOP
40A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 40
secondary to hyphema.12-14 While
the filtering bleb with iridectomy frequently encounters the complication
of closing during the course of the
hyphema resolution, minimal post
surgical events coupled with excellent
short-term IOP reduction has made
it a reasonable alternative for cases
that cannot be managed medically or
through less invasive means.12-14 In
one study, average IOP was lowered
from 40mm Hg to 15mm Hg.12
Clinical Pearls
• A complete medical history is
necessary for successfully managing
hyphema.
• If the dilated view of the posterior segment is obscured, B-scan ultrasonography is indicated to ensure the
absence of vision-threatening retinal
pathology.
• Eyes presenting with traumatic
hyphema must be evaluated for ruptured globe, orbital fracture, retinal
detachment and systemic bleeding
disorders which might exacerbate the
condition.
• Gonioscopy increases the risk of
rebleed and is contraindicated.
• Gonioscopy should be performed
following resolution to assess the
angle’s status and formulate a risk
profile for late traumatic glaucoma.
• Oral analgesic medications must
be limited to those that do not have
anti-platelet effects (no aspirin or
NSAIDs).
• Aminocaproic acid or traexamic
acid antifibrinolytic therapy remains
variably used throughout the community. It can serve as an adjunct in
cases experiencing rebleeding.
1. Walton W, Von Hagen S, Grigorian R, et
al. Management of traumatic hyphema. Surv
Ophthalmol. 2002;47(4):297-334.
2. Recchia FM, Saluja RK, Hammel K, et al.
Outpatient management of traumatic microhyphema.
Ophthalmology. 2002;109(8):1465-70.
3. Rocha KM, Martins EN, Melo LA Jr, et al.
Outpatient management of traumatic hyphema
in children: prospective evaluation. J AAPOS.
2004;8(4):357-61.
4. Mowatt L, Chambers C. Ocular morbidity of
traumatic hyphema in a Jamaican hospital. Eur J
Ophthalmol. 2010;20(3):584-9.
5. Ashaye AO. Traumatic hyphaema: a report of 472
consecutive cases. BMC Ophthalmol. 2008;8(11):24.
6. Ramstead C, Ng M, Rudnisky CJ. Ocular injuries
associated with Airsoft guns: a case series. Can J
Ophthalmol. 2008;43(5):584-7.
7. Alliman KJ, Smiddy WE, Banta J, et al, Ocular trauma and visual outcome secondary to paintball projectiles. Am J Ophthalmol. 2009 Feb;147(2):239-42.
8. Rao LG, Ninan A, Rao KA. Descriptive study on ocular
survival, visual outcome and prognostic factors in open
globe injuries. Indian J Ophthalmol. 2010;58(4):321-3.
9. Wilensky JT. Blood induced secondary glaucomas. Ann Ophthalmol. 1979;11(11):1659-62.
10. Yu T, Dahan E, Yin ZQ, et al. Use of an anterior
chamber maintainer in the surgical management of
traumatic hyphaemas. Clin Experiment Ophthalmol.
2008;36(3):206-8.
11. Pandey P, Sung VC. Gonioaspiration for refractory glaucoma secondary to traumatic hyphema in
patients with sickle cell trait. Ophthalmic Surg Lasers
Imaging. 2010;41(3):386-9.
12. Baig MS, Ahmed J, Ali MA. Role of trabeculectomy in the management of hypertensive traumatic total hyphaema. J Coll Physicians Surg Pak.
2009;19(8):496-9.
13. Graul TA, Ruttum MS, Lloyd MA. Trabeculectomy
for traumatic hyphema with increased intraocular
pressure. Am J Ophthalmol. 1994;117(2):155-9.
14. Verma N. Trabeculectomy and manual clot
evacuation in traumatic hyphaema with corneal blood
staining. Aust N Z J Ophthalmol. 1996;24(1):33-8.
15. Romano PE, Robinson JA. Traumatic hyphema: a
comprehensive review of the past half century yields
8076 cases for which specific medical treatment
reduces rebleeding 62%, from 13% to 5% (P<.0001).
Binocul Vis Strabismus Q. 2000;15(2):175-86.
16. Pollard ZF. No rebleeds in 250 cases of traumatic
hyphema with the Yasuna “No Touch” protocol.
Binocul Vis Strabismus Q. 2000;15(3):250.
17. Wilensky JT. Blood induced secondary glaucomas. Ann Ophthalmol. 1979;11(11):1659-62.
18. Schlote T, Rohrbach M. Traumatic glaucoma—a
survey. Klin Monbl Augenheilkd. 2005;222(10):772-82.
19. Sihota R, Kumar S, Gupta V, et al. Early predictors of traumatic glaucoma after closed globe injury:
trabecular pigmentation, widened angle recess,
and higher baseline intraocular pressure. Arch
Ophthalmol. 2008;126(7):921-6.
20. De Leon-Ortega JE, Girkin CA. Ocular traumarelated glaucoma. Ophthalmol Clin North Am.
2002;15(2):215-23.
21. Herschler J. Trabecular damage due to blunt
anterior segment injury and its relationship to traumatic glaucoma. Trans Sect Ophthalmol Am Acad
Ophthalmol Otolaryngol. 1977;83(2):239-48.
22. Russell SR, Olsen KR, Folk JC. Predictors
of scleral rupture and the role of vitrectomy in
severe blunt ocular trauma. Am J Ophthalmol.
1988;105(3):253-7.
23. Kylstra JA, Lamkin JC, Runyan DK. Clinical predictors of scleral rupture after blunt ocular trauma.
Am J Ophthalmol. 1993;115(4):530-5.
24. Korenfeld MS, Silverstein SM, Cooke DL, et al.
Difluprednate ophthalmic emulsion 0.05% for postoperative inflammation and pain. J Cataract Refract
Surg. 2009;35(1):26-34.
JUNE 15, 2012
6/1/12 3:23 PM
UVEA AND GLAUCOMA
DIURNAL CONTROL OF INTRAOCULAR PRESSURE IN OPEN-ANGLE GLAUCOMA
It has been shown through well-performed clinical trials that
lowering of intraocular pressure (IOP) prevents or delays progressive glaucomatous damage.1,2 Ideally, IOP should be lowered
consistently at all times in order to affect the best outcome and
prognosis for patients. Typically, measurement of IOP occurs during office hours with the patient seated upright in the exam chair.
Often, several IOP measurements would be taken on separate
days, preferably at different hours in the morning and early and
late afternoon in order to understand the diurnal trend of each
patient.
It has long been thought that IOP tends to be highest in the
early morning and decreases throughout the day in most individuals. It was postulated that IOP was lowest while patients sleep, due
to a reduction of aqueous production. However, this information
typically came from studies performed in clinical settings during
normal office hours.
Newer information has provided a better assessment of what
actually happens to IOP during the full diurnal cycle. Nakakura and
colleagues examined patients with glaucoma being treated with
three IOP-reducing medications (latanoprost, a beta blocker, and a
topical carbonic anhydrase inhibitor) and, using Goldmann tonometry with the patients sitting upright, found that the peak IOP
occurred during the night outside of typical office hours in 61% of
tested eyes.3
Liu and colleagues, in an effort to better identify natural diurnal
IOP values, used a sleep laboratory where trained observers using
night vision goggles and a pneumotonometer, could measure IOP
with patients sitting upright in the 16-hour waking cycle and supine
during the eight-hour sleep period.4-6 Measurements of IOP were
taken every two hours in the sitting position during the diurnal/wake
period (7:00 a.m. to 11:00 p.m.) and in the supine position during
the nocturnal/sleep period.4-6 In contrast to the previous thinking that
IOP was lowest during the sleep period, they found that IOP actually
peaked during this time.4-6 This was true for healthy patients as well
as for those with glaucoma.7 The reason for this finding is not clear,
but it is postulated that, when patients are supine, there is a gravitational effect increasing episcleral venous pressure. In order for aqueous to flow, there must be a pressure differential with IOP highest
in the posterior chamber, reducing in the anterior chamber, reducing
further in Schlemm’s canal and beyond. As episcleral venous pressure
rises, the resistance to aqueous outflow increases. The result is an
IOP that rises until it can overcome the backpressure and reestablish
forward flow.
If the IOP is highest when patients sleep in the supine position,
it is likely a person’s highest IOP measurement will remain undiscovered. However, we can speculate that the pressure measured
during typical office hours possibly reflects their lower range of the
diurnal IOP, reasoning that IOP is likely higher when patients sleep
supine. Knowing that IOP is highest while patients sleep supine, it
becomes imperative to choose therapies, both primary and adjunctive, which demonstrate effects evenly throughout the 24-hour
cycle.
It has been well shown that prostaglandin analogs are excellent in reducing IOP both during waking hours as well as during
the supine sleep cycle.8,9 This could possibly be explained by the
fact that prostaglandin analogs increase aqueous outflow through
the uveoscleral pathway, which is independent of episcleral venous
pressure. Nomura and associates and Sit and colleagues found
a sustained IOP-lowering effect of travoprost throughout the
24-hour diurnal cycle.10,11
What is less certain are the effects of other therapies in the
24-hour diurnal cycle. Liu and associates observed that although
0.1% brimonidine monotherapy significantly lowered IOP during
the diurnal/wake period, it did not significantly lower IOP during
the nocturnal/sleep period.12 Similarly, once-daily gel-forming beta
blocker monotherapy failed to provide IOP reduction from the
untreated baseline during the sleep cycle though IOP was significantly reduced during the day.8
When choosing adjunctive therapy to prostaglandin analogs,
considerations for sleep time effects are warranted. It has been
shown that, while brinzolamide and timolol added to latanoprost
have similar ocular hypotensive effects during the waking cycle,
only brinzolamide seems to have an additional adjunctive effect
during the sleep cycle while timolol does not.13-15 Curiously, the
opposite effect was seen with laser trabeculoplasty as an adjunct
to medical therapy. In a group of medically treated open-angle
glaucoma patients, laser trabeculoplasty reduced IOP more consistently during the supine sleep cycle than during the upright diurnal
time period.16
1. Heijl A, Leske MC, Bengtsson B, et al. Early Manifest Glaucoma Trial Group.
Reduction of intraocular pressure and glaucoma progression: results from the Early
Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-79.
2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension
Treatment Study: a randomized trial determines that topical ocular hypotensive
medication delays or prevents the onset of primary open-angle glaucoma. Arch
Ophthalmol. 2002;120(6):701-13.
3. Nakakura S, Nomura Y, Ataka S, Shiraki K. Relation between office intraocular
pressure and 24-hour intraocular pressure in patients with primary open-angle
glaucoma treated with a combination of topical antiglaucoma eye drops. J
Glaucoma. 2007;16(2):201-4.
4. Liu JH, Sit AJ, Weinreb RN. Variation of 24-hour intraocular pressure in healthy
individuals: right eye versus left eye. Ophthalmology. 2005;112(10):1670-5.
5. Liu JH, Kripke DF, Hoffman RE, et al. Nocturnal elevation of intraocular pressure in young adults. Invest Ophthalmol Vis Sci. 1998;39(13):2707-12.
6. Liu JH, Zhang X, Kripke DF, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis
Sci. 2003;44(4):1586-90.
7. Mosaed S, Liu JH, Weinreb RN. Correlation between office and peak nocturnal
intraocular pressures in healthy subjects and glaucoma patients. Am J Ophthalmol.
2005;139(2):320-4.
8. Liu JH, Kripke DF, Weinreb RN. Comparison of the nocturnal effects of
once-daily timolol and latanoprost on intraocular pressure. Am J Ophthalmol.
2004;138(3):389-95.
9. Bagga H, Liu JH, Weinreb RN. Intraocular pressure measurements throughout
the 24 h. Curr Opin Ophthalmol. 2009;20(2):79-83.
10. Nomura Y, Nakakura S, Moriwaki M, et al. Effect of travoprost on 24-hour
intraocular pressure in normal tension glaucoma. Clin Ophthalmol. 2010;4:643-7.
11. Sit AJ, Weinreb RN, Crowston JG, et al. Sustained effect of travoprost on
diurnal and nocturnal intraocular pressure. Am J Ophthalmol. 2006;141(6):1131-3.
12. Liu JH, Medeiros FA, Slight JR, Weinreb RN. Diurnal and nocturnal
effects of brimonidine monotherapy on intraocular pressure. Ophthalmology.
2010;117(11):2075-9.
13. Miura K, Ito K, Okawa C, et al. Comparison of ocular hypotensive effect
and safety of brinzolamide and timolol added to latanoprost. J Glaucoma.
2008;17(3):233-7.
14. Liu JH, Medeiros FA, Slight JR, Weinreb RN. Comparing diurnal and nocturnal
effects of brinzolamide and timolol on intraocular pressure in patients receiving
latanoprost monotherapy. Ophthalmology. 2009;116(3):449-54.
15. Nakamoto K, Yasuda N. Effect of concomitant use of latanoprost and brinzolamide on 24-hour variation of IOP in normal-tension glaucoma. J Glaucoma.
2007;16(4):352-7.
16. Lee AC, Mosaed S, Weinreb RN, et al. Effect of laser trabeculoplasty on nocturnal intraocular pressure in medically treated glaucoma patients. Ophthalmology.
2007;114(4):666-70.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 41
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VITREOUS AND RETINA
DIABETIC RETINOPATHY
Signs and Symptoms
Diabetes mellitus is a disease of broken glucose metabolism.1-26 A microvascular disease, it primarily effects the
capillaries. In the eye, its effects are far
reaching, altering the blood vasculature in the conjunctiva, the neurologic
homeostasis of the cornea, the blood
vasculature of the iris, the fluid dynamics of the lens and the capillary network
of the retina and nerve.1-20 It also has
the potential to affect the central nervous system and the cranial nerves—
notably II, III, IV, V, VI, and VII.15-20
In most instances, patients remain
asymptomatic. Symptoms manifest
ocularly when architectural alterations
impact the macular area producing
reduced acuity or when vitreous hemorrhage or tractional retinal detachment induce catastrophic vision loss or
when ischemic-vascular pathophysiology alters cranial nerves to produce
ophthalmoplegia or lagophthalmos.
An early symptom is fluctuating
visual acuity.13 Increased myopia is
most common (myopic shift) but
hyperopia is possible.13,14 While previously thought to be a process secondary to unstable blood sugar, recent
reports suggest that refractive variation
is secondary to overall disease decompensation rather than fluctuating glucose levels alone.13,14 Swelling within
the crystalline lens can also produce
large sudden shifts in refractive error as
well as premature cataract formation.15
Changes in visual acuity will depend
upon the severity and stage of the disease. Other subtle ocular signs include
injected bulbar conjunctivae and neovascularization of the iris (rubeosis irides) with or without ectropion uvea.
In the retina, weakening of the
arterioles and capillaries results in the
characteristic appearance of intraretinal
dot and blot hemorrhages, exudates,
intraretinal microvascular abnormali42A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 42
ties (IRMA), edema and cotton wool
infarcts. Proliferative diabetic retinopathy occurs as a result of severe
ischemia and manifests as neovascularization of the disc (NVD), neovascularization elsewhere in the retina
(NVE) and neovascularization of the
iris (NVI).1-12,21,23-26
Systemically, patients may complain
of unexplained weight loss despite a
larger than normal appetite (polyphasia),
abnormal thirst (polydypsia) and abnormally frequent urination (polyuria).22
Pathophysiology
Diabetes mellitus is a genetically
influenced group of diseases that share
glucose intolerance.1-4 It is characterized as a disorder of metabolic dysregulation as a result of deficient or
malfunctioning insulin or deficient or
malfunctioning cellular insulin receptors.1-27 Two forms of retinopathy
emerge from the complications of
this process that impair retinal autoregulation: nonproliferative diabetic
retinopathy and proliferative diabetic
retinopathy.1-12,23-27
Nonproliferative diabetic retinopathy is characterized by capillary compromise, intravascular microaneurysms,
IRMA, intraretinal hemorrhages (dot
and blot hemorrhage), intraretinal
lipid leakage (exudates), nerve fiber
layer infarction with axonal stasis (cotton wool patches) and the leakage of
plasma-based fluid (retinal/macular
edema).1-12,23 Sustained hyperglycemia creates elevated levels of biologically active compounds that include
diacylglycerol, histamine, advanced
end-products of glycation, lipoxygenase and nitric oxide. These chemical
mediators trigger the release of protein
kinase C and endothelin as well as
directly induce oxidative damage to
vessels.23 They also directly destabilize
the chemistry of the vitreous humor.23
The result is vascular vasoconstriction,
hypoxia and the concomitant release of
interleukin-6 along with the accumulation of pathological acidic proteins in
the vitreous.23 Interleukin-6 and these
acidic proteins inspire the release of
vascular endothelial growth factors
and increase direct vitreoretinal adhesions.23 As the traction builds and retinal vascular endothelial junctions are
overcome by the chemokines, the inner
blood retinal barrier becomes compromised and intraretinal leakage ensues.23
The influx of water across the blood
retinal barrier cannot be compensated
for by the retinal pigment epithelium
and fluid accumulates.23
Simultaneously, the polyol pathway
enables the formation of sorbitol, a
toxic byproduct of glucose metabolism,
to form in large quantities. Sorbitol
poisons the supportive capillary pericytes, which further induces vascular
leakage.23 When fluid accumulates
within the boundaries articulated by
the National Eye Institute of National
Institutes of Health’s Early Treatment
of Diabetic Retinopathy Study
(ETDRS), the fluid accumulation is
considered to meet the criteria of what
the study termed clinically significant
macular edema (CSME).8-11,23
Proliferative diabetic retinopathy
is the result of chronic, untreated
diabetic retinal disease. Here, thickened, glucose-laden blood, prolonged
vascular insufficiency, capillary nonperfusion, retinal hypoxia and altered
structure induces the formation and
release of vasoproliferative factors
(vascular endothelial growth factor-A:
VEGF-A) that play a role in the genesis of retinal neovascularization.5,6,23
Pigment epithelial derived factor
(PEDF), secreted by adipocytes (adipokine), is a natural antiangiogenesis
molecule that also promotes pericyte
health.23-26 PEDF is secreted less as
the hyperglycemic condition persists,
permitting hypoxia and tumor necrosis factor to rise.24-26 Other growth
factors known to participate in the
JUNE 15, 2012
6/1/12 3:23 PM
Management
When retinal findings consistent
with diabetes are found in an undiagnosed individual a Fasting Blood
Glucose (FBS), Glycosylated hemoglobin and Oral Glucose Tolerance
Test (OGTT) should be ordered from
a general medical practitioner.31 A
physical examination should also be
recommended to determine general
health status as hypertension and dyslipidemia are associated accomplices.32
Researchers have hypothesized that
low levels of erythropoietin (EPO), a
glycoprotein hormone that controls
erythropoiesis or red blood cell production may place patients at increased
risk for retinopathy development.32
EPO is locally expressed and has been
correlated with increased VEGF levels
in eyes with diabetic macular edema
and work is underway to assess the
benefit of EPO injection.32
Non-proliferative diabetic retinopathy, displaying extensive exudates, dot/blot hemorrhages
and macular edema.
Most of the mild non-visionthreatening ocular sequelae of diabetes
resolve spontaneously over the course
of weeks to months following medical control. In cases where there are
large refractive changes, patients may
require a temporary spectacle prescription until the refractive status of the
eyes stabilize. The most important
element of this management is education so that patients are informed that
there may be a need to change the
lenses as the condition evolves. Even
retinal findings can be minimized and
resolved when tight systemic control
is maintained.1,7,12 When retinopathy
threatens the macula and subsequently
visual acuity, or when new blood vessels proliferate, laser photocoagulation
and other retinal surgical modalities
are recommended.1-12
The Diabetic Retinopathy Study
(DRS) has conclusively proven that
panretinal photocoagulation (PRP)
is successful for reducing the risk of
severe vision loss in patients with PDR.
The ETDRS has conclusively
shown that focal/grid laser photocoagulation reduces the risk of moderate
vision loss in patients with CSME.8-11
The ETDRS defined CSME as: (1)
retinal thickening at or within 500 µm
(1/3 of a disc diameter) of the center
of the foveola, (2) exudate at or within
500 µm of the center of the foveola
only if associated with retinal thickening or (3) an area of retinal thicken-
ing one disc diameter or greater in
size, within one disc diameter of the
foveola.8-11 If any of these criteria are
discovered or suspected, regardless of
the acuity, a referral to a retinal specialist is warranted.8-11
New additions to the standard traditional treatment regimens include
treating patients who have significant
retinopathy prior to cataract extraction with grid laser and/or anti-VEGF
injection. This can be done at the time
of cataract extraction with simultaneous
injection of steroid and anti-VEGF
medication. It is also now recommended to use intravitreal anti-VEGF medications for proliferative retinopathy
along with PRP and vitrectomy, as well
as of intravitreal anti-VEGF medications or steroids as a pretreatment for
focal/grid laser photocoagulation and
the use of strategic vitrectomy (viscosurgery) for severe proliferative diabetic
vitreoretinopathy.33-42
Clinical Pearls
• CSME is a visual acuity independent finding and can exist in the presence of 20/20 vision.
• CSME is traditionally identified
through observation, using stereoscopic indirect biomicroscopy (60.00
D, 78.00 D, 90.00 D, Hruby lens or 3
mirror lens); however, optical coherence tomography (OCT) can confirm
suspected cases or identify subtle thickening not detectable with observation
alone.43 OCT technology can also be
used to track macular edema resolution
following treatment.44
• Fluorescein angiography is a
technique used for treatment. It identifies the areas of leakage that require
focal grid laser photocoagulation
after CSME has been diagnosed by
stereoscopic indirect biomicroscopic
observation. Prophylactic laser photocoagulation to prevent proliferative
retinopathy has been proven to be
contraindicated.1,5,6
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 43
VITREOUS AND RETINA
pathogenesis of neovascular growth
include platelet derived growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor
(HGF), transforming growth factor
(TGF), placental endothelial cell
growth factor (PlGF) and connective tissue growth factor (CTGF).26
Other associated molecules include
integrins, angiopoietins, protein
kinase C (PKC), ephrins, interleukins, leptin, angiotensin, monocyte
chemotactic protein (MCP), vascular
cell adhesion molecule (VCAM), tissue plasminogen activator (TPA) and
extracellular matrix metalloproteinases
(ECM-MMPs).26 The result of this
complicated cascade is the formation of fragile fibrovascular vessels
(neovascularization) that scaffold onto
the posterior hyaloid surface of the
vitreous, creating traction, increasing
the risk of vitreous hemorrhage and
tractional retinal detachment.1,5,6,28-30
Proliferative vitreoretinopathy is associated with severe vision loss.1,5,6
43A
6/1/12 3:23 PM
Proliferative diabetic retinopathy, displaying
fibrovascular proliferation, tractional retinal
detachment and vitreal hemorrhages.
• It should also be remembered that
the development of diabetic retinopathy is time dependent. Even in the
face of optimal blood sugar control,
patients with long-standing disease can
be expected to develop some form of
retinopathy eventually.
1. Rosenblatt BL, Benson WE. Diabetic retinopathy.
In: Yanoff M, Duker JS. Ophtalmology 2nd Ed. Mosby,
Philadelphia, 2004: 877-886.
2. Durham JT, Herman IM. Microvascular modifications
in diabetic retinopathy. Curr Diab Rep. 2011;11(4):25364.
3. Zong H, Ward M, Stitt AW. AGEs, RAGE, and diabetic retinopathy. Curr Diab Rep. 2011;11(4):244-52.
4. Nolan CJ, Damm P, Prentki M. Type 2 diabetes
across generations: from pathophysiology to prevention
and management. Lancet. 2011;378 (9786):169-81.
5. The Diabetic Retinopathy Study Research Group.
The Four Risk Factors for Severe Visual Loss in
Diabetic Retinopathy : The Third Report from the
Diabetic Retinopathy Study. Archives of Ophthalmology
1979;97(1):654-55.
6. The Diabetic Retinopathy Study Research Group.
Indications for Photocoagulation Treatment of Diabetic
Retinopathy: Diabetic Retinopathy Study Report, No. 14.
International Ophthalmology Clinics 1987;27(4):239-53.
7. Diabetes Control and Research Group. The effect
of intensive treatment of diabetes on the development
and progression of long-term complications in insulindependent diabetes mellitus. The New England Journal
of Medicine 1993;329(14):977-986.
8. Early Treatment of Diabetic Retinopathy Study.
Focal Photocoagulation Treatment of Diabetic Macular
Edema. Relationship of treatment effects of fluorescein
angiographic and other retinal characteristics at baseline: Early Treatment of Diabetic Retinopathy Study
Report No. 19. Archives of Ophthalmology 1995;113
(9):1144-1155.
9. Early Treatment of Diabetic Retinopathy Study.
Fundus Photographic Risk Factors for Progression
of Diabetic Retinopathy, Early Treatment of Diabetic
Retinopathy, Report No. 12. Ophthalmology 1991;98
(5):823-833.
10. Early Treatment of Diabetic Retinopathy Study
Research Group. Photocoagulation for Diabetic Macular
Edema:Early Treatment of Diabetic Retinopathy Study
44A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 44
Report 1. Archives of Ophthalmology 1985;103(12):2531.
11. Early Treatment of Diabetic Retinopathy Study
Research Group. Photocoagulation for Diabetic Macular
Edema. Archives of Ophthalmology 1985;103(12):17961806.
12. Diabetes Control and Complications Trial Research
Group. Progression of Retinopathy with Intensive versus
Conventional Treatment in the DCCT. Ophthalmology
1995;102(4): 647-661.
13. Klein BE, Lee KE, Klein R. Refraction in adults with
diabetes. Arch Ophthalmol. 2011;129(1):56-62.
14. Agardh E, Hellgren KJ, Bengtsson B. Stable refraction and visual acuity in diabetic patients with variable
glucose levels under routine care. Acta Ophthalmol.
2011;89(2):107-10.
15. de Fine Olivarius N, Siersma V, Almind GJ, Nielsen
NV. Prevalence and progression of visual impairment in
patients newly diagnosed with clinical type 2 diabetes:
a 6-year follow up study. BMC Public Health. 2011;11
(2):80.
16. Tu MC, Chang YY, Lin TK. Recurrent multiple
cranial neuropathies in a diabetic patient. Acta Neurol
Taiwan. 2010;19(3):208-12.
17. Giuliari GP, Sadaka A, Chang PY, Cortez RT.
Diabetic papillopathy: current and new treatment
options. Curr Diabetes Rev. 2011;7(3):171-5.
18. Uluduz D, Bozluolcay M, Ince B, Kiziltan M.
Simultaneous multiple cranial nerve neuropathies and
intravenous immunoglobulin treatment in diabetes mellitus. Neurol India. 2006;54(3):308-9.
19. Pritchard N, Edwards K, Shahidi AM, Sampson
GP, et al. Corneal markers of diabetic neuropathy. Ocul
Surf. 2011;9(1):17-28.
20. Bosco D, Plastino M, Bosco F, Consoli A, et al.
Bell’s palsy: a manifestation of prediabetes?Acta Neurol
Scand. 2011;123(1):68-72.
21. Agurto C, Murray V, Barriga E, Murillo S, et al.
Multiscale AM-FM methods for diabetic retinopathy
lesion detection. IEEE Trans Med Imaging. 2010(2):50212.
22. Straka M. Oral manifestations of diabetes mellitus
and influences of periodontological treatment on diabetes mellitus. Bratisl Lek Listy. 2011;112(7):416-20.
23. Bhagat N, Grigorian RA, Tutela A, Zarbin MA.
Diabetic macular edema: pathogenesis and treatment.
Surv Ophthalmol. 2009;54(1):1-32.
24. Yamagishi S, Matsui T. Advanced glycation end
products (AGEs), oxidative stress and diabetic retinopathy. Curr Pharm Biotechnol. 2011;12(3):362-8.
25. Famulla S, Lamers D, Hartwig S, et al. Pigment
epithelium-derived factor (PEDF) is one of the most
abundant proteins secreted by human adipocytes and
induces insulin resistance and inflammatory signaling in
muscle and fat cells. Int J Obes (Lond). 2011;35(6):76272.
26. Praidou A, Androudi S, Brazitikos P, et al.
Angiogenic growth factors and their inhibitors in diabetic
retinopathy. Curr Diabetes Rev. 2010;6(5):304-12.
27. Skov Jensen P, Jeppesen P, Bek T. Differential
diameter responses in macular and peripheral retinal
arterioles may contribute to the regional distribution
of diabetic retinopathy lesions. Graefes Arch Clin Exp
Ophthalmol. 2011;249(3):407-12.
28. Shirshikov IuK. Acoustic studies in proliferative diabetic retinopathy. Vestn Oftalmol. 2001;117(6):23-5.
29. Krasnov MM, Sdobnikova SV, Fedorov AA,
Stoliarenko GE. Posterior hyaloid membrane as structural base of growth of neovascular tissue in proliferative
diabetic retinopathy. Vestn Oftalmol. 1998;114(3):16-
20.
30. Arumí JG, Boixadera A, Martínez-Castillo V,
Corcóstegui B. Transconjunctival sutureless 23-gauge
vitrectomy for diabetic retinopathy. Curr Diabetes Rev.
2009;5(1):63-6.
31. Lapolla A, Mosca A, Fedele D. The general use of
glycated haemoglobin for the diagnosis of diabetes and
other categories of glucose intolerance: still a long way
to go. Nutr Metab Cardiovasc Dis. 2011;21(7):467-75.
32. Lim JW, Han JR. Aqueous humour levels of vascular endothelial growth factor and erythropoietin in
patients with diabetic macular oedema before and
after intravitreal erythropoietin injection. Clin Experiment
Ophthalmol. 2011;39(6):537-44.
33. Wahab S, Ahmed J. Management of cataract with
macular oedema due to diabetes mellitus type-II and
hypertension with grid laser prior to surgery and intravitreal bevacizumab (Avastin) preoperatively. J Pak Med
Assoc. 2010;60(10):836-9.
34. Akinci A, Muftuoglu O, Altınsoy A, Ozkılıc E.
Phacoemulsification with intravitreal bevacizumab and
triamcinolone acetonide injection in diabetic patients
with clinically significant macular edema and cataract.
Retina. 2011;31(4):755-8.
35. Augustin AJ. Upcoming therapeutic advances in
diabetic macular edema: an intravitreal dexamethasone drug delivery system. Expert Opin Drug Deliv.
2011;8(2):271-9.
36. Schwartz SG, Flynn HW Jr. Fluocinolone acetonide
implantable device for diabetic retinopathy. Curr Pharm
Biotechnol. 2011;12(3):347-51.
37. Bandello F, Battaglia Parodi M, et al. Steroids
as part of combination treatment: the future for the
management of macular edema? Ophthalmologica.
2010;224 Suppl 1:41-5.
38. Gillies MC, McAllister IL, Zhu M, Wong W, et al.
Intravitreal triamcinolone prior to laser treatment of diabetic macular edema: 24-month results of a randomized controlled trial. Ophthalmology. 2011;118(5):86672.
39. Synek S, Vojniković B. Intravitreal bevacizumab with
or without triamcinolone for refractory diabetic macular
oedema. Coll Antropol. 2010;34 Suppl 2:99-103.
40. Nadal J, Capella MJ. Treatment of proliferative diabetic retinopathy using viscosurgery with vital dye. Arch
Ophthalmol. 2011;129(10):1358-60.
41. di Lauro R, De Ruggiero P, di Lauro MT, et al.
Intravitreal bevacizumab for surgical treatment of severe
proliferative diabetic retinopathy. Graefes Arch Clin Exp
Ophthalmol. 2010;248(6):785-91.
42. Virgili G, Menchini F, Murro V, Peluso E. Optical
coherence tomography (OCT) for detection of macular
oedema in patients with diabetic retinopathy. Cochrane
Database Syst Rev. 2011;6;(7):CD008081.
43. Vemala R, Koshy S, Sivaprasad S. Qualitative and
quantitative OCT response of diffuse diabetic macular oedema to macular laser photocoagulation. Eye
(Lond).2011;25(7):901-8.
CENTRAL SEROUS
CHORIORETINOPATHY
Signs and Symptoms
Patients with central serous chorioretinopathy (CSC) usually present
with complaints of sudden onset dis-
JUNE 15, 2012
6/1/12 3:23 PM
or less) is often noted in the affected
eye. Funduscopic examination shows
a distinct, round or oval serous elevation of the macula with a loss of the
foveal light reflex. An underlying area
of RPE detachment may be seen concurrently in about 10% of patients.20,21
Associated findings can include cystoid
macular degeneration, retinal atrophy,
and RPE tears (sick RPE or gutter syndrome), especially in chronic
cases.22-24 There exists the possibility
of choroidal neovascularization (CNV)
as well.25,26 Cases involving CNV are
typically associated with a poor visual
outcome. Today, optical coherence
tomography (OCT) is often used to
confirm the diagnosis of CSC. OCT
classically shows a bullous neurosensory retinal detachment from the underlying choroid, separated by an optically
empty zone. Fluorescein angiography
will typically demonstrate a focal point
of fluorescein leakage under the serous
detachment that gradually expands to
fill the entire lesion; it is sometimes
referred to as a “smokestack” or “ink
blot” hyperfluorescent pattern.1
Pathophysiology
While a great deal of research has
been conducted in this area, CSC
remains incompletely understood.
CSC appears to have a multifactorial
etiology, with various systemic associations and a complex pathogenesis.
The primary dysfunction appears to be
localized ischemia and/or inflammation at the level of the choriocapillaris,
which leads to hyperpermeability; this
in turn results in decompensation of
the retinal pigment epithelium, causing a focal detachment of the overlying
neurosensory retina.19,20 Biochemical
changes are likely at the root of this
process. In patients with CSC, serum
levels of catecholamines and glucocorticoids appear to be elevated, and this
is believed to have a direct influence
on the integrity of Bruch’s mem-
brane.17-19,27 Based on these observations, it is reasonable to speculate
that adrenergic receptors within the
choroidal circulation are involved in
the pathogenesis of CSC. Stimulation
of adrenergic receptors often results in
release of secondary messengers, (e.g.,
cyclic adenosine monophosphate) and
this may produce the vascular or RPE
changes that result in CSC.28
Recently, an association between
CSC and Helicobacter pylori has been
reported.29-30 H. pylori is a gram
negative bacterium that resides in the
gastrointestinal tract; it has been associated with a number of ocular conditions including dry eye, ocular rosacea,
adnexal tumors and several forms of
glaucoma.31 Researchers have proposed
that the immune responses generated
against H. pylori result in the genesis
of antibodies and proteins that have
the capacity to alter the endothelial
vascular wall.29 Such processes may
contribute to the development of CSC
in some patients.
Management
Most cases of CSC are self-limiting
over a period of three to 12 months.1,11
The prognosis for visual recovery is
excellent, with most regaining their
pre-event acuity. Upon diagnosing the
condition, any corticosteroid therapy
should be immediately discontinued,
if possible. A consultation with the
patient’s primary care physician may be
indicated in cases involving steroidal
anti-inflammatory agents for systemic
conditions and steroidal inhalers for
asthma. Fully 90% of CSC cases
resolve spontaneously following the
cessation of steroids.32 While the acute
phase of CSC is usually self-limiting,
the condition may be recurrent in as
many as 50% of affected individuals.33
These patients often demonstrate cystic
yellow lesions in the macula known
as lemon-drop nodules. Lemon-drop
nodules are indicative of mild RPE
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 45
VITREOUS AND RETINA
tortion or blurring of central vision.
They may report metamorphopsia,
decreased color perception, or even a
relative central scotoma. The presentation is typically unilateral, although
bilateral cases have been reported, and
the likelihood of subsequent involvement of the fellow eye may be as
high as 40%.1-3 There is typically no
pain and no history of recent trauma.
Patients often have a history of using
corticosteroids (topical, injectable,
or oral), sympathomimetic agents,
or medications for erectile dysfunction.1-9 Other contributory elements
may include antibiotics, uncontrolled
hypertension, alcohol, allergic respiratory disease and obstructive sleep
apnea.2,10 However, steroids are considered to be the greatest precipitating factor, at least from an exogenous
point of view.2
Patients with CSC are typically
younger, with most cases occurring
between the ages of 25 and 50.11
According to one report, the mean
age at diagnosis is 41 years.12 Men
are afflicted far more frequently than
women, with an incidence ratio of
about 6:1.1,2,12,13 There are few, if
any, racial predilections. Patients of
European and Asian descent appear to
be affected equally.1,2,14 Reports differ
regarding those of African descent;
some sources suggest that these individuals are diagnosed less frequently
with CSC, while others report no
differences.1,15 Perhaps the most wellknown association with CSC is the
psychological profile known as “Type
A” personality. These individuals,
who are described as exhibiting the
characteristics of time urgency, aggressiveness, hostility and competitiveness,
seem to be particularly predisposed to
developing CSC.16-19
Clinical evaluation of the patient
with CSC reveals no external signs
of ocular disease or inflammation.
Mild hyperopic refractive shift (+1.25
45A
6/1/12 3:23 PM
detachment. They may also stimulate
RPE hyperplasia.
In non-remitting or recurrent cases,
focal laser photocoagulation has been
utilized in an attempt to arrest the
leakage.34 Laser debridement of the
damaged RPE allows adjacent RPE
cells to assume their function at the
site of the lesion.1 However, focal laser
therapy does not necessarily ensure
improvement in visual acuity; it merely
hastens recovery and diminishes the
likelihood of recurrence.1,34 There are
risks associated with this treatment,
most notably iatrogenic damage to
the fovea and subsequent formation
of CNV.1,25,26 For these reasons, most
practitioners will employ laser therapy
only in cases that fail to respond
within a reasonable period of time,
recurrent cases, or cases in which the
patients are overtly symptomatic and
insist on definitive treatment.
Photodynamic therapy (PDT) with
verteporfin has also been used successfully in the treatment of CSC; it has
been demonstrated to improve visual
acuity, reduce leakage on fluorescein
angiography, reduce subretinal fluid
as demonstrated by OCT and foster
choroidal remodeling with decreased
choroidal permeability.34-36 Other
experimental treatments for CSC have
shown modest success, including antiVEGF treatment and transpupillary
thermotherapy.37,38 Oral therapy with
corticosteroid antagonists, adrenergic
receptor antagonists and carbonic
anhydrase inhibitors (e.g., acetazolamide) has also been documented, but
with limited efficacy.1
Clinical Pearls
• An experienced, astute clinician
can often diagnose CSC based solely
upon the history and chief complaint.
A young, anxious, otherwise healthy
patient who presents with unilateral
metamorphopsia of recent onset represents the classic presentation for CSC.
46A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 46
Bullous macular elevation in central serous
chorioretinopathy.
• Patients presenting with CSC
for the first time should be reassured,
counseled as to the natural course of
the condition, and monitored every
three to four weeks for three to six
months as resolution occurs. A referral
to retinology is indicated to rule out
the need for fluorescein angiography.
If the patient fails to resolve after six
months, one should consider more
aggressive therapy, i.e., laser photocoagulation, PDT, or anti-VEGF.
• While CSC is classically thought
of as a male disorder, it must be noted
that both genders may be affected.
Women account for between 12% and
28% of the affected population.39,40
Moreover, pregnancy is a recognized
risk factor for CSC, with an identified odds ratio of 7.1 in a case-control
study of 312 patients.2 Hence, it is
important to consider this condition
in pregnant women who present with
sudden onset of visual complaints.
1. Ross A, Ross AH, Mohamed Q. Review and
update of central serous chorioretinopathy. Curr Opin
Ophthalmol. 2011;22(3):166-73.
2. Haimovici R, Koh S, Gagnon DR, et al. Risk factors for
central serous chorioretinopathy: a case-control study.
Ophthalmology. 2004;111(2):244-9.
3. Kleinberger AJ, Patel C, Lieberman RM, Malkin BD.
Bilateral central serous chorioretinopathy caused by
intranasal corticosteroids: a case report and review of the
literature. Laryngoscope. 2011;121(9):2034-7.
4. Baumal CR, Martidis A, Truong SN. Central serous
chorioretinopathy associated with periocular corticosteroid injection treatment for HLA-B27-associated iritis.
Arch Ophthalmol. 2004;122(6):926-8.
5. Fernandez CF, Mendoza AJ, Arevalo JF. Central
serous chorioretinopathy associated with topical dermal
corticosteroids. Retina. 2004;24(3):471-4.
6. Koyama M, Mizota A, Igarashi Y, et al. Seventeen
cases of central serous chorioretinopathy associated
with systemic corticosteroid therapy. Ophthalmologica.
2004 Mar;218(2):107-10.
7. Fraunfelder FW, Fraunfelder FT. Central serous
chorioretinopathy associated with sildenafil. Retina.
2008;28(4):606-9.
8. Gordon-Bennett P, Rimmer T. Central serous
chorioretinopathy following oral tadalafil. Eye (Lond).
2012;26(1):168-9.
9. Michael JC, Pak J, Pulido J, et al. Central serous chorioretinopathy associated with administration of sympathomimetic agents. Am J Ophthalmol. 2003;136(1):1825.
10. Kloos P, Laube I, Thoelen A. Obstructive sleep
apnea in patients with central serous chorioretinopathy.
Graefes Arch Clin Exp Ophthalmol. 2008;246(9):1225-8.
11. Marcuson J, Riley T. Central serous chorioretinopathy. Optometry. 2008;79(5):241-51.
12. Kitzmann AS, Pulido JS, Diehl NN, Hodge DO,
Burke JP. The incidence of central serous chorioretinopathy in Olmsted County, Minnesota, 1980-2002.
Ophthalmology. 2008;115(1):169-73.
13. Todd KC, Hainsworth DP, Lee LR, et al. Longitudinal
analysis of central serous chorioretinopathy and sex. Can
J Ophthalmol. 2002;37(7):405-8.
14. How AC, Koh AH. Angiographic characteristics of
acute central serous chorioretinopathy in an Asian population. Ann Acad Med Singapore. 2006;35(2):77-9.
15. Desai UR, Alhalel AA, Campen TJ, et al. Central
serous chorioretinopathy in African Americans. J Natl
Med Assoc. 2003;95(7):553-9.
16. Yannuzzi LA. Type A behavior and central serous
chorioretinopathy. Trans Am Ophthalmol Soc.
1986;84:799-845.
17. Wynn PA. Idiopathic central serous chorioretinopathy—a physical complication of stress? Occup Med
(Lond). 2001;51(2):139-40.
18. Zakir SM, Shukla M, Simi ZU, et al. Serum cortisol
and testosterone levels in idiopathic central serous chorioretinopathy. Indian J Ophthalmol. 2009;57(6):419-22.
19. Gemenetzi M, De Salvo G, Lotery AJ. Central serous
chorioretinopathy: an update on pathogenesis and treatment. Eye (Lond). 2010;24(12):1743-56.
20. Mudvari SS, Goff MJ, Fu AD, et al. The natural
history of pigment epithelial detachment associated with central serous chorioretinopathy. Retina.
2007;27(9):1168-73.
21. Chang MA, Bressler SB. Photodynamic therapy for
chronic pigment epithelial detachment in central serous
chorioretinopathy. Can J Ophthalmol. 2009;44(2):221-2.
22. Iida T, Yannuzzi LA, Spaide RF, et al. Cystoid macular degeneration in chronic central serous chorioretinopathy. Retina. 2003;23(1):1-7.
23. Wang MS, Sander B, Larsen M. Retinal atrophy
in idiopathic central serous chorioretinopathy. Am J
Ophthalmol. 2002;133(6):787-93.
24. Shanmugam MP, Bhende M. Retinal pigment epithelial tears associated with idiopathic central serous chorioretinopathy. Indian J Ophthalmol. 2000;48(4):315-7.
25. Konstantinidis L, Mantel I, Zografos L, Ambresin A.
Intravitreal ranibizumab in the treatment of choroidal neovascularization associated with idiopathic central serous
chorioretinopathy. Eur J Ophthalmol. 2010;20(5):955-8.
26. Chan WM, Lai TY, Liu DT, Lam DS. Intravitreal bevacizumab (avastin) for choroidal neovascularization secondary to central serous chorioretinopathy, secondary to
JUNE 15, 2012
6/1/12 3:24 PM
RETINAL DETACHMENT
Signs and Symptoms
Retinal detachments occur in
approximately 6.1:100,000 persons
in the general phakic population.1-3
The rates between men and women
are similar world wide, with a slight
preponderance for female gender with
myopia.2-4 There are three recog-
nized forms of retinal detachment.1-9
These include: rhegmatogenous
retinal detachment (RRD-resulting
from a retinal break), exudative or
serous retinal detachment (ERDresulting from fluid accumulation
under the sensory retina without a
retinal break) and tractional retinal
detachment (TRD-resulting from
the pull of proliferative fibrovascular vitreal strands).1-10 Any type of
retinal detachment may be initially
asymptomatic. Rhegmatogenous
retinal detachments may remain
asymptomatic up to discovery.11,12 In
symptomatic RRD, patients report
photopsiae (flashes of light), floating spots, peripheral visual field loss
(curtain phenomenon) and depending
upon the involvement of the macula,
central blurring of vision with or without metamorphopsia.1,13 There are
anecdotal reports of exudative retinal
detachments producing photopsiae
(flashing purple lights) but the common symptoms experienced by these
patients are vision loss and metamorphopsia consistent with the degree of
macular involvement, with or without
a visual field deficit.5,14
Tractional retinal detachments
have the capacity to produce the same
symptoms as rhegmatogenous and
exudative retinal detachments. They
may also remain asymptomatic until
central vision is threatened.5,15 Pain is
not a feature of any retinal detachment
as the tissue has no pain receptors. In
fact, the only sensory receptors in the
retina are for light; hence the sensation of flashing lights experienced
by patients from mechanical vitreoretinal tractional forces.12 Any pain
encountered by a patient experiencing any form of retinal detachment is
secondary to an associated cause such
as headache, iritis, corneal abrasion,
uveitis or raised intraocular pressure
and not the detachment itself.1,5,16,17
Extensive unilateral retinal detachment
VITREOUS AND RETINA
punctate inner choroidopathy, or of idiopathic origin. Am
J Ophthalmol. 2007;143(6):977-983.
27. Sun J, Tan J, Wang Z, et al. Effect of catecholamine
on central serous chorioretinopathy. J Huazhong Univ
Sci Technolog Med Sci. 2003;23(3):313-6.
28. Jampol LM, Weinreb R, Yannuzzi L. Involvement
of corticosteroids and catecholamines in the pathogenesis of central serous chorioretinopathy: a rationale for new treatment strategies. Ophthalmology.
2002;109(10):1765-6.
29. Giusti C. Association of Helicobacter pylori with
central serous chorioretinopathy: hypotheses regarding
pathogenesis. Med Hypotheses. 2004;63(3):524-7.
30. Misiuk-Hojło M, Michałowska M, Turno-Krecicka A.
Helicobacter pylori—a risk factor for the developement
of the central serous chorioretinopathy. Klin Oczna.
2009;111(1-3):30-2.
31. Figura N, Franceschi F, Santucci A, et al. Extragastric
manifestations of Helicobacter pylori infection.
Helicobacter. 2010;15 Suppl 1:60-8.
32. Sharma T, Shah N, Rao M, et al. Visual outcome
after discontinuation of corticosteroids in atypical severe
central serous chorioretinopathy. Ophthalmology.
2004;111(9):1708-14.
33. Wong R, Chopdar A, Brown M. Five to 15 year
follow-up of resolved idiopathic central serous chorioretinopathy. Eye (Lond). 2004;18(3):262-8.
34. Lim JW, Kang SW, Kim YT, Chung SE, Lee SW.
Comparative study of patients with central serous
chorioretinopathy undergoing focal laser photocoagulation or photodynamic therapy. Br J Ophthalmol.
2011;95(4):514-7.
35. Taban M, Boyer DS, Thomas EL, et al. Chronic central serous chorioretinopathy: photodynamic therapy. Am
J Ophthalmol. 2004;137(6):1073-80.
36. Chan WM, Lam DS, Lai TY, et al. Choroidal vascular
remodelling in central serous chorioretinopathy after
indocyanine green guided photodynamic therapy with
verteporfin: a novel treatment at the primary disease
level. Br J Ophthalmol. 2003;87(12):1453-8.
37. Schaal KB, Hoeh AE, Scheuerle A, et al. Intravitreal
bevacizumab for treatment of chronic central serous
chorioretinopathy. Eur J Ophthalmol. 2009;19(4):613-7.
38. Kawamura R, Ideta H, Hori H. Transpupillary thermotherapy for atypical central serous chorioretinopathy. Clin
Ophthalmol. 2012;6:175-9.
39. Castro-Correia J, Coutinho MF, Rosas V, Maia J.
Long-term follow-up of central serous retinopathy in 150
patients. Doc Ophthalmol. 1992;81(4):379-86.
40. Spaide RF, Campeas L, Haas A, et al. Central
serous chorioretinopathy in younger and older adults.
Ophthalmology. 1996;103(12):2070-9; discussion
2079-80.
Bullous, rhegmatogenous retinal detachment.
will produce a relative afferent pupillary defect.1,16 Intraocular pressure may
be notably reduced in eyes with acute
retinal detachment.19-21
Clinical observation of fresh RRD
usually reveals a clumping of pigment
cells within the vitreous (Shaffer’s
sign/tobacco dust) adjacent to the
retinal break.1,22 An area of white or
grayish elevated retina may be seen
adjacent to the instigating retinal break
secondary to influx of subretinal fluid
(SRF).4 If a significant area of the
retina is involved it may appear bullous
and undulating. A rhegmatogenous
detachment is produced by a retinal
break that allows liquefied vitreous to
separate the sensory retina from the
retinal pigment epithelium (RPE)
through poorly understood posterior
segment fluid mechanics.21 Osmotic
and oncotic pressures help keep the
retina in place.22 As such, RRD do not
change positions when body posture
is altered.23 RRD do shift and return
to their original orientation with quick
eye movements.1 Associated findings
of RRD may include posterior vitreous
detachment and preretinal or vitreal
hemorrhage.24-26 Retinal pigment
epithelial hyperplasia may be noted in
cases of long-standing retinal detachment of any kind (pigment demarcation line). Increased RPE density is a
feature of attempted self repair.1,5,27
ERD appear as focal, serous elevations of the retina in the absence of
retinal breaks.5,28-34 Because the fluid
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 47
47A
6/1/12 3:25 PM
is contained underneath an intact
neurosensory boundary, the bullous
separation possesses the characteristic
of following gravity, shifting position with changes in posture and
eye movement.1,5 Ophthalmoscopic
observation reveals a smooth, translucent, dome-shaped protrusion of the
retina along with variable other signs
secondary to the causative etiology
(blood, exudate, or serosanguinous
fluid).5 Causes of ERD include Coats’
disease, age-related macular degeneration, idiopathic central serous chorioretinopathy (ICSC), fluid exudation
from chroidal tumors and VogtKoyanagi-Harada syndrome, among
numerous others.5,28-34
TRD is always associated with
fibrovascular vitreal strands and membranes.1,35-37 The clinical appearance
of these detachments is varied with
tangential fibrovascular bands anchoring into the vitreous body and extending to the dis-inserted retina.1,35-37
The tractional membranes may
encircle intact retina, resulting in a
“pseudo-hole” appearance. TRDs are
dense and immobile, as compared with
ERD and RRD. Any pathology that
can induce posterior segment ischemia
and retinal neovascularization can
proceed to TRD. The common underlying causes include diabetes, vein
occlusion, ocular ischemic syndrome,
retinopathy of prematurity and sickle
cell disease.35-39
Pathophysiology
All retinal detachments involve a
dissection of the sensory retina from
its underlying RPE layer by SRF.140 In rhegmatogenous detachments
this fluid is thought to be composed
of liquefied vitreous, which gains
access to the subretinal space via a
retinal break.1,22 In exudative detachments, the fluid is derived from the
choroid, passing through a breach in
Bruch’s membrane.5,28-34 The origin
48A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 48
of the subretinal fluid in tractional
retinal detachments is similar with
slightly varied mechanisms. Generally,
altered balance between the passive
and active movement of SRF induces
RD progression.1 While all retinal
detachments have the potential to
produce visual scotomata (depending
upon their size and location), it is the
involvement of the macular region,
where apoptotic mechanisms deteriorate macular photoreceptors, that will
determine the extent of acuity loss.40
Retinal breaks are the predisposing
factor in patients with rhegmatogenous
retinal detachment.1,22-27 These may
occur spontaneously from preexisting
conditions or as a result of ocular trauma.1-3 Some of the common entities
associated with RRD include lattice
degeneration, flap tears, atrophic holes,
operculated retinal breaks and acquired
retinoschisis with both inner and outer
holes.1,3,4,41 As the retinal tissue loses
its connection to the RPE, it becomes
edematous and dysfunctional.22 The
detached retina loses its oxygen supply
and relies on anaerobic pathways to
metabolize glucose.22 Long-duration
retinal detachments feature increased
lactic acid and dextrose concentrations.23 Phospholipids are also
increased in the SRF, reflecting retinal
organelle degradation.23 Eventually,
photoreceptor death occurs within 48
to 72 hours unless surgical intervention
is employed.23,40
Exudative retinal detachments
occur in association with subretinal
disorders which damage the RPE
layer.5,28-34 Transudation of fluid
from the choroidal reservoir through
Bruch’s membrane and a breach in
the RPE overcomes the eye’s natural
mechanisms for deturgescing the plasma solution, causing it to build under
the photoreceptors. When the threshold is reached it causes them to disinsert from the RPE.5,23,28-34 Affected
by gravity, as the fluid accumulates,
the detachment will shift with eye
and head movements. However,
since the density of fluid affecting the
retina changes with movement, no
particular area of the retina is continuously affected.5 This may explain why
patients with ERD have final functional outcomes that are better than
those with RRD or TRD.5,28-34
Tractional retinal detachments
occur in the presence of proliferative
vitreoretinopathies.1,35-39 The etiology
of TRD involves fibrotic scaffolding
of the vitreous along proliferative vascular networks, which through vitreal
shrinkage, induce strong anterior tractional forces.39,42-44 RPE cell proliferation and migration are believed to play
a role in the pathogenesis.43 Findings
suggest that the vitreous contributes
modulators that stimulate RPE cells
along with macrophages, fibroblasts
and glial cells to interact with constituents of the extracellular matrix
such as fibronectin, vitronectin, and
factor XIII.43,44 These mechanisms
induce the formation of membranes
that capture the sensory retina and
forcibly separate it from the underlying
RPE.39,42-44 Unlike rhegmatogenous
or exudative retinal detachments which
tend to occur acutely, TRD often
develop slowly. When positioned
peripherally TRD may not be noticed
by the patient until visual acuity is
compromised by the underlying disease process.
Management
Retinal detachments demand repair
and treatment of both the retina and
the underlying cause.1-49 Patients
presenting with an acute onset RRD
involving or threatening the macula
warrant an immediate and emergent
referral to a retinal surgeon. Fresh
RRD should be repaired within 24
to 48 hours; chronic or long-standing
RRD or RRD that do not threaten the
macula should be addressed within one
JUNE 15, 2012
6/1/12 3:27 PM
band is used to indent the eye at
the location of detachment.59 The
intent of the buckle (explant-on top
of the sclera, implant-placed into a
scleral dissection) is to eliminate the
vitreoretinal traction that induced
the retinal tear and to prevent fluid
seepage underneath the retinal
break.1,59 This process also encourages RPE pumping to eliminate the
SRF. Drainage of SRF via syringe is
controversial with some believing it
is not necessary and others believing
it is crucial.58 Raised IOP, choroidal
detachment, diplopia, macular edema
and macular pucker are all potential
complications.59
Pneumatic retinopexy utilizes an
intravitreal gas bubble (usually perfluoropropane, C3F8 or sulfahexafluoride)
to achieve reattachment of the retina
for RRD.60-62 This technique is performed under local anesthesia and is
more common for treating smaller,
superiorly located RRD.60 Careful eye
and head positioning are important
postoperatively to ensure resolution.60
In certain instances, silicone oil tamponade may be favorable to either of
the aforementioned techniques.63 The
use of polydimethylsiloxane (PDMS)
as a silicone oil endotamponade has
become a standard in retinal surgery.63
In cases of complicated inferior and
posterior retinal detachment heavy silicone oils are sometimes considered.63
A randomized prospective clinical trial
(HSO study) comparing heavy and
standard silicone oil in patients with
PVR of the lower retina have failed to
demonstrate superiority of a heavy oil
tamponade.64
Exudative detachments, because
of their nature, generally require less
intervention than RRD.5,7 ERDs may
resolve spontaneously or following
management of the underlying condition.5,7,23,28-34 This may involve oral
antibiotics in cases involving infection,
high dose oral or vitreal injectable/
implantable corticosteroids in the case
of inflammatory disorders, oral acetazolomide in cases of ICSC and radiation therapy and/or local resection in
the case of intraocular neoplasms.65-67
In cases involving choroidal neovascularization laser photocoagulation,
photodynamic therapy and vascular
endothelial growth factor inhibitor
injections may all be used.65,68
Tractional retinal detachments
are more difficult to manage than
either RRD or ERD. Managing
the underlying cause is an essential
precursor.39,35-37 Endolaser scatter
photocoagulation must be employed
directly to the retina to correct the
underlying inciting retinal cause for
new vessel growth.39 Surgical repair of
TRD involves pars plana vitrectomy
to remove the traction and the fibrovascular membranes along with the
inciting vitreal cytokines. Gas or oil
tamponade is used to promote retinal
reattachment.63,64,69
Clinical Pearls
• All patients presenting with
symptoms of retinal detachment or a
predisposing history (peripheral retinal thinning or breaks, blunt ocular
trauma, proliferative diabetic vitreoretinopathy, etc.) must undergo a thorough dilated fundus evaluation, with
scleral indentation where appropriate.
• Fresh rhegmatogenous detachments should be immediately referred
for evaluation of surgical intervention.
• The effect of gravity increases the
risk for superior detachments to spread.
• Conservative surgical management may be indicated for partial or
sectoral RRD (laser barrier).
1. Wilkinson CP. Rhegmatogenous retinal detachment. In: Yanoff M, Duker JS. Ophthalmology 2nd Ed.
Mosby, Philadelphia, 2004: 982-989.
2. Haimann MH, Burton TC, Brown CK. Epidemiology
of retinal detachment. Arch Ophthalmol.
1982;100(2):289-92.
3. Mitry D, Charteris DG, Fleck BW, Campbell H, et al.
The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 49
VITREOUS AND RETINA
week of diagnosis.50,51 Small peripheral
RRD secondary to atrophic holes or
RRD secondary to small tears displaying minimal SRF may be managed
with barrier laser photocoagulation
or cryopexy.1,45-49 While cryopexy
has been reported to provoke a more
aggressive postoperative inflammatory response, its outcomes over time
compared to laser barrier treatment are
similar.49 An advantage of cryopexy
over laser procedures is that it is generally less expensive and does not have
to be repeated.49 Larger RRD require
surgical repair using procedures that
include vitrectomy, scleral buckling,
needle aspiration, laserpexy, cryopexy,
pneumatic retinopexy and intraocular
silicone oil tamponade.13,52-55
Vitrectomy has been investigated
as a principle treatment method for
RRD.56-58 Vitrectomy seems to
allow improved control of more
complicated situations.57 The Scleral
Buckling vs. Primary Vitrectomy in
Rhegmatogenous Retinal Detachment
Study (SPR study) is a prospective,
randomized, multicenter study comparing primary vitrectomy with or
without additional scleral buckling
to scleral buckling alone.56,58 In the
pseudophakic subgroup, no difference in functional outcome was seen;
however, better anatomical results
with a lower rate of retina-affecting
reoperations was observed in the vitrectomy group.56-58 Based on this data,
primary vitrectomy combined with a
scleral buckle is the method of choice
in complicated retinal detachment in
pseudophakic patients. In contrast,
primary vitrectomy does not seem to
offer an advantage over scleral buckling
in phakic patients.56,58 The primary
drawback of vitrectomy is its significant propensity to create cataract and
postpone complete visual recovery.58
Scleral buckling is accomplished
under general anesthesia where a
soft silicone sponge or hard silicone
49A
6/1/12 3:27 PM
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4. Ung T, Comer MB, Ang AJ, et al. Clinical features and surgical management of retinal detachment secondary to round retinal holes. Eye (Lond).
2005;19(6):665-9.
5. Anand R. Serous detachment of the neural retina. In:
Yanoff M, Duker JS. Ophthalmology 2nd Ed. Mosby,
Philadelphia, 2004:990-996.
6. Saika S, Yamanaka O, Okada Y, et al. TGF beta
in fibroproliferative diseases in the eye. Front Biosci
(Schol Ed). 2009;1(6):376-90.
7. Srećković SB, Janićijević-Petrović MA, Stefanović
IB, et al. Bilateral retinal detachment in a case of preeclampsia. Bosn J Basic Med Sci. 2011;11(2):129-31.
8. Fluieraru R. Ocular, anatomical and functional
changes in rhegmatogenous retinal detachment.
Oftalmologia. 2008;52(2):39-43.
9. Gemenetzi M, De Salvo G, Lotery AJ. Central serous
chorioretinopathy: an update on pathogenesis and
treatment. Eye (Lond). 2010;24(12):1743-56.
10. Mitry D, Fleck BW, Wright AF, et al. Pathogenesis
of rhegmatogenous retinal detachment: predisposing
anatomy and cell biology. Retina. 2010;30(10):156172.
11. Ahmad N, West J. Current opinion on treatment
of asymptomatic retinal detachments. Eye (Lond).
2007;21(9):1179-85.
12. Brod RD, Flynn HW Jr, Lightman DA.
Asymptomatic rhegmatogenous retinal detachments.
Arch Ophthalmol. 1995;113(8):1030-2.
13. Colucciello M. Rhegmatogenous retinal detachment. Phys Sportsmed. 2009;37(2):59-65.
14. Kim YY, Flaxel CJ. Factors influencing the visual
acuity of chronic central serous chorioretinopathy.
Korean J Ophthalmol. 2011;25(2):90-7.
15. Creuzot-Garcher C, Wolf S. Macular edema.
Miscellaneous. Dev Ophthalmol. 2010;47(1):183-98.
16. Waters T, Vollmer L, Sowka J. Proliferative vitreoretinopathy as a late complication of blunt ocular
trauma. Optometry. 2008;79(4):197-202.
17. Beran DI, Murphy-Lavoie H. Acute, painless vision
loss. J La State Med Soc. 2009;161(4):214-6, 218-23.
18. Uysal Y, Mutlu FM, Sobaci G. Ocular Trauma
Score in childhood open-globe injuries. J Trauma.
2008;65(6):1284-6.
19. Tan HS, Mura M, Oberstein SY, de Smet MD.
Primary retinectomy in proliferative vitreoretinopathy.
Am J Ophthalmol. 2010;149(3):447-52.
20. Grigoropoulos VG, Benson S, Bunce C, Charteris
DG. Functional outcome and prognostic factors in 304
eyes managed by retinectomy. Graefes Arch Clin Exp
Ophthalmol. 2007;245(5):641-9.
21. Lin YC, Chang WH, Yang CM. Complications and
management of post-vitrectomy circumferential retinal
detachment. J Formos Med Assoc. 2009;108(4):333-6.
22. Machemer R. Pathogenesis and classification
of massive periretinal proliferation. Br J Ophthalmol.
1978;62(11):737-47.
23. Quintyn JC, Brasseur G. Subretinal fluid in primary
rhegmatogenous retinal detachment: physiopathology
and composition. Surv Ophthalmol. 2004;49(1):96-108.
24. Hollands H, Johnson D, Brox AC, Almeida D.
Acute-onset floaters and flashes: is this patient at risk
for retinal detachment? JAMA. 2009;302(20):2243-9.
25. Margo CE, Harman LE. Posterior vitreous detachment. How to approach sudden-onset floaters and
flashing lights. Postgrad Med. 2005;117(3):37-42.
26. Mitry D, Singh J, Yorston D, et al. The predisposing pathology and clinical characteristics in the
Scottish retinal detachment study. Ophthalmology.
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2011;118(7):1429-34.
27. Hara A, Nakagomi Y. Analysis of glycosaminoglycans of subretinal fluid in rhegmatogenous retinal
detachment--preliminary report. Jpn J Ophthalmol.
1995;39(2):137-42.
28. Mennel S, Meyer CH, Peter S, Schmidt JC, et al.
Current treatment modalities for exudative retinal hamartomas secondary to tuberous sclerosis: review of the
literature. Acta Ophthalmol Scand. 2007;85(2):127-32.
29. Vrabec TR, Augsburger JJ. Exudative retinal
detachment due to small noncalcified retinal astrocytic
hamartoma. Am J Ophthalmol. 2003;136(5):952-4.
30. Perez MA, Shechtman DL, Gurwood A. The continuum of primary retinal telangiectasia. Optometry.
2011;82(3):158-65.
31. Shields JA, Shields CL, Honavar SG, Demirci H.
Clinical variations and complications of Coats' disease
in 150 cases: the 2000 Sanford Gifford Memorial
Lecture. Am J Ophthalmol. 2001;131(5):561-71.
32. Wang GH, Zhang J, Zhang D, et al. Value of threedimensional optical coherence tomography and fundus
photochromy in correlating the fluorescein leaking sites
of acute central serous chorioretinopathy. Med Princ
Pract. 2011;20(3):283-6.
33. Lim JH, Lee YN, Kim YS, et al. Vogt-KoyanagiHarada disease occurring during pegylated interferon-α
2b and ribavirin combination therapy for chronic hepatitis C. Korean J Hepatol. 2011;17(1):61-5.
34. Errera MH, Fardeau C, Cohen D, et al. Effect of the
duration of immunomodulatory therapy on the clinical
features of recurrent episodes in Vogt-KoyanagiHarada disease. Acta Ophthalmol. 2011;89(4):e35766.
35. Newman DK. Surgical management of the late
complications of proliferative diabetic retinopathy. Eye
(Lond). 2010;24(3):441-9.
36. Fletcher EL, Downie LE, Ly A, et al. A review of the
role of glial cells in understanding retinal disease. Clin
Exp Optom. 2008;91(1):67-77.
37. Jalil A, Dhawahir-Scala FE, Jones NP.
Nonprogressive tractional inferior retinal elevation in intermediate uveitis. Ocul Immunol Inflamm.
2010;18(1):60-3.
38. Micelli Ferrari T, Furino C, Lorusso VV, et al.
Three-port lens-sparing vitrectomy for aggressive
posterior retinopathy of prematurity: early surgery
before tractional retinal detachment appearance. Eur J
Ophthalmol. 2007;17(5):785-9.
39. Ebroon DA, Bearelly S, Jampol LM. Proliferative
retinopathies. In: Yanoff M, Duker JS. Ophthalmology
2nd Ed. Mosby, Philadelphia, 2004: 907-911.
40. Lo AC, Woo TT, Wong RL, Wong D. Apoptosis
and other cell death mechanisms after retinal
detachment: implications for photoreceptor rescue.
Ophthalmologica. 2011;226(1); Suppl 1:10-17.
41. Martínez-Castillo V, Boixadera A, Verdugo A, et
al. Rhegmatogenous retinal detachment in phakic
eyes after posterior chamber phakic intraocular lens
implantation for severe myopia. Ophthalmology.
2005;112(4):580-5.
42. Glaser BM, Cardin A, Biscoe B. Proliferative vitreoretinopathy. The mechanism of development of vitreoretinal traction. Ophthalmology. 1987;94(4):327-32.
43. Kirchhof B, Sorgente N. Pathogenesis of proliferative vitreoretinopathy. Modulation of retinal pigment
epithelial cell functions by vitreous and macrophages.
Dev Ophthalmol. 1989;16(1):1-53.
44. Wiedemann P, Weller M, Heimann K. Proliferative
vitreoretinopathy: new discoveries in pathophysiology
and therapy. Klin Monbl Augenheilkd. 1990;197(5):355-
61.
45. Shukla D, Maheshwari R, Kim R. Barrage laser
photocoagulation for macula-sparing asymptomatic
clinical rhegmatogenous retinal detachments. Eye
(Lond). 2007;21(6):742-5.
46. Hwang JF, Chen SN. Demarcation laser photocoagulation of macular sparing retinal detachments in
teenagers. Retina. 2008;28(10):1487-92.
47. Eliott D, Hauch A, Kim RW, Fawzi A. Retinal dialysis and detachment in a child after airbag deployment.
J AAPOS. 2011;15(2):203-4.
48. Lira RP, Takasaka I, Arieta CE, et al. Cryotherapy
vs laser photocoagulation in scleral buckle surgery: A randomized clinical trial. Arch Ophthalmol.
2010;128(12):1519-22.
49. Veckeneer M, Van Overdam K, Bouwens D, Feron
E, et al. Randomized clinical trial of cryotherapy versus
laser photocoagulation for retinopexy in conventional retinal detachment surgery. Am J Ophthalmol.
2001;132(3):343-7.
50. Henrich PB, Priglinger S, Klaessen D, et al.
Macula-off retinal detachment--a matter of time? Klin
Monbl Augenheilkd. 2009;226(4):289-93.
51. Mowatt L, Shun-Shin GA, Arora S, Price N. Macula
off retinal detachments. How long can they wait before
it is too late? Eur J Ophthalmol. 2005;15(1):109-17.
52. Greven CM. Retinal breaks. In: Yanoff M, Duker
JS. Ophthalmology 2nd Ed. Mosby, Philadelphia,
2004: 978-981.
53. Kitchens JW. Modified external needle drainage of
subretinal fluid in the management of rhegmatogenous
retinal detachment using a “guarded needle” approach.
Arch Ophthalmol. 2011;129(7):949-51.
54. Bourla DH, Bor E, Axer-Siegel R, et al. Outcomes
and complications of rhegmatogenous retinal detachment repair with selective sutureless 25-gauge pars
plana vitrectomy. Am J Ophthalmol. 2010;149(4):630634.
55. Al-Khairi AM, Al-Kahtani E, Kangave D, Abu
El-Asrar AM. Prognostic factors associated with outcomes after giant retinal tear management using perfluorocarbon liquids. Eur J Ophthalmol. 2008;18(2):270-7.
56. Mehta S, Blinder KJ, Shah GK, Grand MG. Pars
plana vitrectomy versus combined pars plana vitrectomy and scleral buckle for primary repair of rhegmatogenous retinal detachment. Can J Ophthalmol.
2011;46(3):237-41.
57. Heimann H, Bartz-Schmidt KU, Bornfeld N, et al.
Primary pars plana vitrectomy. Techniques, indications,
and results. Ophthalmologe. 2008;105(1):19-26.
58. Azad RV, Chanana B, Sharma YR, Vohra R.
Primary vitrectomy versus conventional retinal detachment surgery in phakic rhegmatogenous retinal detachment. Acta Ophthalmol Scand. 2007;85(5):540-5.
59. Williams GA. Scleral buckling surgery. In: Yanoff
M, Duker JS. Ophthalmology 2nd Ed. Mosby,
Philadelphia, 2004: 786-791.
60. Davis MJ, Mudvari SS, Shott S, Rezaei KA. Clinical
characteristics affecting the outcome of pneumatic retinopexy. Arch Ophthalmol. 2011;129(2):163-6.
61. Saw SM, Gazzard G, Wagle AM, et al. An
evidence-based analysis of surgical interventions for
uncomplicated rhegmatogenous retinal detachment.
Acta Ophthalmol Scand. 2006t;84(5):606-12.
62. Chan CK, Lin SG, Nuthi AS, Salib DM. Pneumatic
retinopexy for the repair of retinal detachments: a
comprehensive review (1986-2007). Surv Ophthalmol.
2008;53(5):443-78.
63. Engelmann K, Herbrig E. Different endotamponade agents and their clinical indications. Klin Monbl
JUNE 15, 2012
6/1/12 4:29 PM
RETINAL PIGMENT EPITHELIAL
(RPE) DETACHMENT
Signs and Symptoms
Serous retinal pigment epithelial
detachment (PED) occurs when the retinal pigment epithelium (RPE) becomes
separated from the Bruch’s membrane.1-6 The process occurs asymptomatically unless the macula is affected.
It is often associated with diseases that
can produce choroidal neovascularization.1-6 Concurrent ocular conditions
such as age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), retinal angiomatous
proliferation (RAP), idiopathic central
serous chorioretinopathy (ICSC), ocular
histoplasmosis syndrome (OHS) or vitreomacular traction syndrome (VMTS)
are common associations.7-12 PED is
also an associated complication of laser
photocoagulation and vascular endothelial growth factor (VEGF) inhibitor
injection.2,13,14 Systemically, tubulointerstitial nephritis and uveitis syndrome
(TINU) has been linked to posterior
segment features that include bilateral
vitritis and RPE detachments.15 The
condition has also been documented to
Focal RPE detachment nasal to the macula.
occur idiopathically.16,17 Patients who
experience PED within the macular
area will report sudden, painless blurry
vision, metamorphopsia, micropsia or
positive scotomas.1-6 Other associated
clinical and epidemiologic findings will
depend upon the underlying cause.
For example, in cases involving ICSC
males outnumber females with many
patients experiencing hyperopia and
delayed retinal recovery time upon
photostress test.18,19
The ophthalmoscopic appearance
of PED will depend upon its etiology.1-17,20 Each clinical and fluorescein
angiographic likeness is unique to
the specific cause.20 A PED caused
by subretinal hemorrhage will appear
as a small, dark, elevated subretinal
nodule and will demonstrate a fluorescein pattern consistent with blockage
throughout the angiogram.20 Serous
PED appears as a single, creamy yellow, well-circumscribed round or oval
subretinal lesion demonstrating a fluorescein pattern of fast filling hyperfluorescence contained within the boundaries of the attached RPE.20 Drusenoid
PED appear similar to coalesced soft
drusen and demonstrate a fluorescein
pattern of staining with fading over
the course of the angiogram without evidence of leakage or ooze.20
Fibrovascular PED exhibit mottled and
elevated subretinal irregularities with
fluorescein patterns that demonstrate
a slow stippling hyperfluorescence
that increases in size and intensity
over the course of the angiogram.20
There may be pooling of the dye in the
recirculation phase with evidence of
lacy-leakage in cases that have occurred
secondary to choroidal neovascularization (CNV).20 Overlying RPE defects
(clumping or mottling) are commonplace in cases of longstanding PED
that have spontaneously resolved.
Lesions may vary in size from 1/5 of
a disc diameter (DD) to over 5 DD,
but most are less than 1 DD.2,3,5-7,914,16,17,20,21 The small size is due to the
fact that the RPE is tightly adherent to
Bruch’s membrane and fluid does not
easily extravasate between these two
layers. Leakage into the neurosensory
retina occurs only in cases of concurrent RPE junction failure with central
serous retinal detachment.1,4,9,19
Pathophysiology
RPE detachment is a non-specific
anatomical alteration that may result
from any number of vitreo-choroidal
disorders.1-24 A definitive pathomechanism underlying the development
of PED has not yet been completely
elucidated.24 One theory suggests
that the PED separates from Bruch’s
membrane as a result of increased
choroidal pressure.24 A contrasting
view, related to AMD, is that CNV
forms and contracts producing scarring, which in turn produces a secondary tractional tear.24 An alternative
pathogenetic theory hypothesizes that
an underlying disease (or idiopathic
condition) sets the stage for reduced
hydraulic conductivity of Bruch’s
membrane.10,11,22,23 Here, increased
deposition of lipids, fibrin, enhanced
collagen cross-linking and alteration in
the ratio of tissue-dissolving enzymes
and their inhibitors contribute to the
RPE release.10,22,23 Serous PED result
from idiopathic, AMD-related and
ICSC etiologies. In selected cases the
mechanics of neovascular vessel formation produces fibrovascular PED.23,24
In cases where the pathophysiologic
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 51
VITREOUS AND RETINA
Augenheilkd. 2008;225(2):138-45.
64. Joussen AM, Rizzo S, Kirchhof B, et al. Heavy
silicone oil versus standard silicone oil in as vitreous
tamponade in inferior PVR (HSO Study): interim analysis. Acta Ophthalmol. 2011;89(6):483-9.
65. Arevalo JF, Espinoza JV. Single-session combined
photodynamic therapy with verteporfin and intravitreal anti-vascular endothelial growth factor therapy
for chronic central serous chorioretinopathy: a pilot
study at 12-month follow-up. Graefes Arch Clin Exp
Ophthalmol. 2011;249(8):1159-66.
66. Ossewaarde-van Norel J, Berg EM, Sijssens KM,
Rothova A. Subfoveal serous retinal detachment in
patients with uveitic macular edema. Arch Ophthalmol.
2011;129(2):158-62.
67. Matsuo T, Himei K, Ichimura K, Yanai H, et al.
Long-term effect of external beam radiotherapy of optic
disc hemangioma in a patient with von Hippel-Lindau
disease. Acta Med Okayama. 2011;65(2):135-41.
68. Mandal S, Naithani P, Venkatesh P, Garg S.
Intravitreal bevacizumab (avastin) for circumscribed
choroidal hemangioma. Indian J Ophthalmol.
2011;59(3):248-51.
69. Shukla D, Kanungo S, Prasad NM, Kim R. Surgical
outcomes for vitrectomy in Eales’ disease. Eye (Lond).
2008;22(7):900-4.
51A
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mechanisms are amplified by subretinal neovascular or capillary rupture,
hemorrhagic PED ensue. When soft
lipofuscin coalesce to create an environment that erodes the RPE barrier
junction, drusenoid PED occur.10,20
Ischemia and hypoxia have been
implicated in the pathophysiology of
AMD. These processes share a possible common thread in the pathogenesis of PED.22 The common
pathologic feature of all diseases that
produce PED is impaired retinal oxygen metabolism.22 Confluent drusen,
serous or hemorrhagic retinal detachment, retinal edema, vitreoretinal
adhesion and other disease processes
may all contribute to relative retinal
hypoxia by increasing retinal elevation and the retinal distance from the
choriocapillaris.22 This mechanism
results in impaired diffusion and convection of oxygen towards the retina.22
Hypoxia-inducible-factor is known to
exist in subretinal neovascularization
and hypoxia is the main stimulus for
the production of VEGF.22 Further,
thickening of Bruch’s membrane and
any detachment of the retina or RPE
increases the distance between the
choriocapillaris and the retina, reducing the oxygen flux from the choroid
to the outer retina.22 Retinal elevation
and choroidal ischemia can combine
forces to reduce choroidal oxygen
delivery to the outer retina and produce retinal hypoxia.22 Hypoxia leads
to production of VEGF leading to
neovascularization and tissue edema,
creating the potential for RPE breakdown, PED and a cycle that has the
potential to result in CNV formation
before or after PED.22
An interesting association has
recently surfaced linking ICSC with
the Helicobacter pylori (HP) infection.25
In one case, a recurrence of ICSC
was associated with HP-positivity and
improvements of both retinal findings
and visual acuity were significantly cor52A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 52
related with a successful eradication of
the bacterium.25 In a second case, the
prevalence of HP infection was found
to be significantly higher in ICSCaffected subjects compared to age- and
sex-matched controls from the same
country.25 ICSC seems to be a disease
of choroidal microcirculation dysfunction.25 In fact, several vascular abnormalities, such as localized vasoconstriction and impaired fibrinolysis have been
demonstrated in ICSC.25 Focal occlusion of the choriocapillaries, decreased
foveal choroidal blood flow, secondary
RPE defects and serous macular detachment are all consequences.25
AMD, choroidal neovascular
membranes, high myopia, hereditary
choroidal degeneration, OHS and
tumors of the choroid have all been
identified as precipitating conditions
in the development of RPE detachment.7-11,23-26 Uncomplicated idiopathic serous detachments of the RPE
often resolve spontaneously.
Management
There is no direct or interventional
treatment for PED. Those caused by
more complicated processes associated with generalized damage to the
choriocapillaris may be complicated
by hemorrhage, choroidal neovascular
membrane formation and disciform
scarring.2,3,5-7,9-14,16,17,20,21
Treatment is directed at the
underlying cause. If there is an ocular
infection or inflammation it must be
diagnosed and managed. All PED,
especially those secondary to AMD
must undergo investigation for CNV
(optical coherence tomographyOCT, fluorescein angiography-FA).
If CNV is detected, it can be treated
with injectable therapy or laser surgery.6,13,14,23 If there is no CNV, and
drusen or choroidal atrophy are present, vitamin therapy can be attempted
to arrest high risk drusen and CNV
formation.27,28 Full macular transloca-
tion (FMT) with 360° retinotomy has
been examined with optimism as a
solution for patients with PED where
anti-VEGF therapy has been unresponsive or is contraindicated.29
The treatment for PED secondary to ICSC begins with treating the
underlying cause of the ICSC. Once
CNV has been ruled out, monitoring
with a home Amsler grid, cessation of
any causative medication (i.e., steroids),
oral antibiotic therapy for suspected HP
infection, aspirin therapy (100mg p.o.
q.d. then 100mg p.o. q-other-d every
five months), photocoagulation, photodynamic therapy and oral finasteride
therapy (inhibitor of dihydrotestosterone
synthesis) are all possible options.25,30-32
Most patients under the age of 55
who present with small serous PED
without evidence of other retinal or
choroidal disease typically recover
without intervention.23 Older patients
who manifest PED without angiographic evidence of choroidal neovascularization have a higher risk of
developing CNV during their lifetime.
These cases require careful semiannual dilated funduscopic examination
as well as home observation with an
Amsler grid.1,2
Clinical Pearls
• Approximately 90% of cases of
PED have or will manifest concurrent
serous neurosensory retinal detachment over the natural history of the
disorder.
• The presentation of PED requires
the clinician to rule out ICSC, CNV,
malignant choroidal tumors, choroidal
hemangioma and Best’s disease (vitelliform dystrophy). History and angiography are the most helpful factors in
making this differential diagnosis.
• PED in patients over 55 years of
age should be considered secondary to
choroidal neovascular membrane until
proven otherwise. Prompt fluorescein
angiography is suggested.
JUNE 15, 2012
6/1/12 3:31 PM
dence of central serous chorioretinopathy in Olmsted
County, Minnesota, 1980-2002. Ophthalmology.
2008;115(1):169-73.
20. Martidis A, Tennant MT. Age-related macular
degeneration. In: Yanoff M, Duker JS. Ophthalmology
2nd Ed. Mosby, Philadelphia, 2004: 925-933.
21. Loukianou E, Kisma N, Hamilton R. Complete
resolution of a giant pigment epithelial detachment secondary to exudative age-related macular
degeneration after a single intravitreal ranibizumab
(lucentis) injection: results documented by optical
coherence tomography. Case Report Ophthalmol.
2010;1(2):110-3.
22. Stefánsson E, Geirsdóttir A, Sigurdsson H.
Metabolic physiology in age related macular degeneration. Prog Retin Eye Res. 2011;30(1):72-80.
23. Symeonidis C, Kaprinis K, Manthos K, et al.
Central serous chorioretinopathy with subretinal
deposition of fibrin-like material and its prompt
response to ranibizumab injections. Case Report
Ophthalmol. 2011;2(1):59-64.
24. Lommatzsch A. Pigment epithelial detachment
in exudative macular degeneration: clinical characteristics and therapeutic options. Ophthalmologe.
2010;107(12):1115-22.
25. Giusti C. Association of Helicobacter pylori with
central serous horioretinopathy: hypotheses regarding
pathogenesis. Med Hypotheses. 2004;63(3):524-7.
26. Keane PA, Liakopoulos S, Chang KT, et al.
Comparison of the optical coherence tomographic
features of choroidal neovascular membranes in
pathological myopia versus age-related macular
degeneration, using quantitative subanalysis. Br J
Ophthalmol. 2008 Aug;92(8):1081-5.
27. Krishnadev N, Meleth AD, Chew EY. Nutritional
supplements for age-related macular degeneration.
Curr Opin Ophthalmol. 2010;21(3):184-9.
28. Millen AE, Voland R, Sondel SA, et al. Vitamin
D status and early age-related macular degeneration in postmenopausal women. Arch Ophthalmol.
2011;129(4):481-9.
29. Polito A, Cereda M, Romanelli F, Pertile G.
Macular translocation with 360 degrees retinotomy
for management of retinal pigment epithelial tear:
long-term results. Br J Ophthalmol. 2011;95(1):74-8.
30. Caccavale A, Imparato M, Romanazzi F, et al.
A new strategy of treatment with low-dosage acetyl
salicylic acid in patients affected by central serous
chorioretinopathy. Med Hypotheses. 2009;73(3):4357.
31. Wang M, Munch IC, Hasler PW, et al. Central
serous chorioretinopathy. Acta Ophthalmol.
2008;86(2):126-45.
32. Forooghian F, Meleth AD, Cukras C, et al.
Finasteride for chronic central serous chorioretinopathy. Retina. 2011;31(4):766-71.
RETINITIS PIGMENTOSA
Signs and Symptoms
Retinitis pigmentosa (RP) is a
group of inherited disorders affecting
one in 3,000 to 7,000 people.1,2 It is
characterized by abnormalities of the
photoreceptors (rods and cones) or
the retinal pigment epithelium (RPE)
of the retina, which lead to progressive visual loss.1-14 The predominant
symptom is bilateral progressive
visual field and acuity loss often proceeding to blindness.1-13 These diseases are transmitted through genetic
pedigrees echoing all known modes
of inheritance.3 To date, 45 causative
genes/loci have been identified in
non syndromic RP (for the autosomal dominant, autosomal recessive,
X-linked, and digenic forms).3 The
most common form of RP is a rodcone dystrophy.3
Syndromic RP is defined as the
disease and its variations with associated groupings of signs, symptoms
and systemic findings involving
one or more organ systems.3,14 The
disease process has many variations
with the potential for both early
or delayed onset.15 Most patients
with RP are diagnosed in the second or third decade of life.5-12
Bardet-Biedl syndrome (BBS) and
Usher syndrome (US) are the most
prevalent syndrome forms involving
RP.1,3,7,11,12,16,17 Together they make
up almost a quarter of the patients
with RP.12 Bardet-Biedl syndrome is
defined by the association of retinopathy, obesity, hypogonadism, renal
dysfunction, postaxial polydactyly and
mental retardation.1,3,11,12 Usher syndrome is characterized by the combination of congenital or early-onset
sensorineural deafness, RP and variable degrees of vestibular dysfunction.11,12,16 Kearns-Sayre syndrome
(KS) is a rare disorder consisting
of ptosis, limited movement of the
eyes and atypical retinal pigmentary
changes.7,17 Occasionally KS manifests other neurological and endocrinological symptoms such as ataxia,
dementia, diabetes and hyperaldosteronism.7 Refsum’s syndrome is characterized by defective peroxisomal
alpha oxidation of phytanic acid with
JUNE 15, 2012 R E V IE W O F O P T O ME T R Y
001_ro0612_hndbk.indd 53
VITREOUS AND RETINA
1. Anand R. Serous detachment of the neural retina.
In: Yanoff M, Duker JS. Ophthalmology 2nd Ed.
Mosby, Philadelphia, 2004: 990-996.
2. Chang LK, Sarraf D. Tears of the retinal pigment
epithelium: an old problem in a new era. Retina.
2007;27(5):523-34.
3. Barkmeier AJ, Carvounis PE. Retinal pigment epithelial tears and the management of exudative agerelated macular degeneration. Semin Ophthalmol.
2011;26(3):94-103.
4. Wang M, Munch IC, Hasler PW, et al. Central
serous chorioretinopathy. Acta Ophthalmol.
2008;86(2):126-45.
5. Wu PC, Chen YJ, Kuo HK. Retinal pigment epithelial tear after intravitreous triamcinolone acetonide
injection for fibrovascular pigment epithelial detachment. Chang Gung Med J. 2011;34(3):320-5.
6. Pepple K, Mruthyunjaya P. Retinal pigment epithelial detachments in age-related macular degeneration: classification and therapeutic options. Semin
Ophthalmol. 2011;26(3):198-208.
7. Spaide RF. Enhanced depth imaging optical
coherence tomography of retinal pigment epithelial
detachment in age-related macular degeneration. Am
J Ophthalmol. 2009;147(4):644-52.
8. Uyama M, Wada M, Nagai Y, et al. Polypoidal
choroidal vasculopathy: natural history. Am J
Ophthalmol. 2002;133(5):639-48.
9. Gupta P, Gupta V, Dogra MR, et al. Morphological
changes in the retinal pigment epithelium on spectraldomain OCT in the unaffected eyes with idiopathic
central serous chorioretinopathy. Int Ophthalmol.
2010;30(2):175-81.
10. Wasmuth S. Pathogenetic concepts for pigment epithelial detachment in exudative AMD.
Ophthalmologe. 2010;107(12):1109-14.
11. Georgalas I, Heatley C, Ezra E. Retinal pigment
epithelium detachment associated with vitreomacular traction syndrome-case report. Int Ophthalmol.
2009;29(5):431-3.
12. Lommatzsch A, Heimes B, Gutfleisch M, et al.
Retinal angiomatous proliferation with associated
pigment epithelium detachment: anti-VEGF therapy.
Ophthalmologe. 2011;108(3):244-51.
13. Gutfleisch M, Heimes B, Schumacher M, et
al. Long-term visual outcome of pigment epithelial
tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD.Eye (Lond).
2011;25(9):1181-6.
14. Barkmeier AJ, Carvounis PE. Retinal pigment epithelial tears and the management of exudative agerelated macular degeneration. Semin Ophthalmol.
2011;26(3):94-103.
15. Sheth HG, Laverde-Konig T, Raina J. TINUassociated retinal pigment epithelium detachments:
a possible novel posterior segment feature. Int
Ophthalmol. 2009;29(3):179-81.
16. Schütt F, Schaal K, Dithmar S. Photodynamic
therapy for bilateral idiopathic detachment of the
RPE. Klin Monbl Augenheilkd. 2007;224(7):603-5.
17. Gass JD, Bressler SB, Akduman L, et al.
Bilateral idiopathic multifocal retinal pigment epithelium detachments in otherwise healthy middleaged adults: a clinicopathologic study. Retina.
2005;25(3):304-10.
18. Ito Y, Horiguchi M, Miyake Y, Awaya S.
Extrafoveal photostress recovery testing with a
scanning laser ophthalmoscope. Jpn J Ophthalmol.
1997;41(4):255-9.
19. Kitzmann AS, Pulido JS, Diehl NN, et al. The inci-
53A
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clinical features that include retinitis
pigmentosa, polyneuropathy, anosmia and hearing loss.12,13,18 BassenKornzweig disease is an autosomal
recessive disorder featuring altered
lipoprotein metabolism characterized
by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis
from early infancy.19,20
Patients with RP may present
with varying symptoms, which are
often gradual and insidious with
many patients failing to recognize the
advancing manifestations until the
disease has progressed significantly.1-24
When symptoms are reported, they
initially include difficulty with night
vision (nyctalopia), difficulty with
vision in bad weather as well as loss of
peripheral vision.1-8,23 Many patients
with RP will also experience visually
debilitating photopsia as the disorder
progresses.21,22 This phenomenon is
believed to represent aberrant electrical impulses from the degenerating
retina.21 Central visual acuity is generally not affected until very late stages,
although variants have been encountered that cause devastating macular
compromise early in the disease course
(e.g., X-linked recessive RP, RP
inversa).8,23,24 Color vision typically
remains intact as long as visual acuity
is better than 20/40.8,23 Most patients
experience their greatest reductions in
central vision between the ages 50 to
80 years.5-13
The ophthalmoscopic appearance of
RP involves attenuation of the retinal
arterioles, intraneural retinal pigment
(bone spicules) in the midperipheral
retina and at perivascular locations,
thinning and atrophy of the RPE in
the mid and far periphery, preservation of macular integrity (except in
the condition of RP inversa [macular
presentation] and RP sine pigmento
[without pigment]), gliotic atrophy of
the axons composing the optic nerve
54A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 54
(waxy pallor) and choriocapillaris atrophy with increased visibility into the
choroid.5-13,24-28 There is a correlation
with acquired optic disc drusen in RP.9
In the traditional forms of RP, the
appearance and function of the macula
and optic nerve remain normal in the
early stages of the disease’s development; however, tissue changes in
response to the pathology may provoke
preretinal gliosis (cellophane maculopathy), which may lead to macular hole,
cystoid macular edema and focal RPE
defects.29,30 Additional ophthalmologic
findings within the vast expression of
RP include ectopic lentis, microspherophakia (Weill-Marchesani syndrome),
atypical cataract formation, pigment
cells in the vitreous, posterior vitreous detachment and associated vitreous hemorrhage.31-34 Most patients
with retinitis pigmentosa are myopic
although high hyperopia has been
reported.34-36 There is also a correlation
with keratoconus.37
Pathophysiology
The pathophysiology of retinitis
pigmentosa is complex.38-46 The common theme of the disease, in virtually
all forms, stems from genetic and
mitochondrial defects that produce
disturbances in the RPE leading to
destruction of the photoreceptors’
outer segment disc membranes.2,8,45
The resultant accumulation of metabolic by-products creates disruption of
the normal retinal function advancing
varying combinations of lipofuscin
deposition, retinal gliosis, photoreceptor loss, choriocapillaris occlusion,
choroidal atrophy and RPE hyperplasia.2,8,44,45 As the RPE alterations
progress, the blood-retina barrier
becomes eroded, resulting in intraretinal and subretinal leakage. The clinical
manifestation is the loss of visual field,
nyctalopia, and eventual formation of
cystic macular edema and acuity loss in
later stages of the disorder.24-30 There
are many recognized forms of retinitis
pigmentosa and while most present
with similar findings and outcomes,
some presentations are atypical.44
Classification of RP may be made on
the basis of inheritance pattern (autosomal dominant, autosomal recessive,
X-linked, simplex-no family members,
multiplex-multiple genes), age of
onset (congenital, childhood onset,
juvenile onset, adult onset), predominant photoreceptor involvement (rodcone, cone-rod), or location of retinal
involvement (central, pericentral, sectoral, peripheral).5-13,24,44-47
Electrodiagnostic testing remains
the gold standard for diagnosis.1-3,24,26,38-40 In RP, both the electroretinogram (ERG) and multifocal
electroretinogram (mERG) show
significantly diminished red, white,
blue and 30hz flicker waves.35,36 The
electro-oculogram (EOG) and dark
adaptometry remain as staples in diagnosis and monitoring.5-13,39,40 New
testing being evaluated by researchers
includes pupillary light reflex evaluation in conjunction with optical coherence tomography as an indicator of
photoreceptor dysfunction in patients
with advancing typical retinitis pigmentosa.41-43 Fundus autofluorescence
(FAF), which measures the density
of lipofuscin granules, has emerged
as a potential tool as well.25,41-43
Genetic testing can determine the
risk of expression in offspring and
identify specific gene defects in the
affected.1-4,9-25
Management
There is no known treatment to
diminish or reverse the progressive
retinal dysfunction encountered in
retinitis pigmentosa.1-53 Management
therefore is three pronged: 1) Prompt
diagnosis, 2) Rectify the treatable
associated ocular and systemic complications (i.e., refractive error, cataract
formation, macular edema, vitreous
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brightness, contrast, color, movement,
shape, resolution visual field size.5
No trial patients have shown signs of
implant rejection, infection, inflammation, erosion, neovascularization,
retinal detachment, or migration.5
Animal models have led to the
development of therapeutic strategies aimed at identifying and curing specific genetic disorders (gene
therapy).1-4,44-47 Newly developed
algorithms are being designed to
slow down or even stop the process of photoreceptor degeneration. These include growth factors,
calcium blocker applications and
vitamin supplements. The use of
stem or precursor cells is also being
investigated.5,6,9,54 The newest treatment options include trophic factor
therapy, visual cycle inhibitors and
cell transplantation.55 A radically different approach has been given the
name neural prosthetics (“artificial
vision”).55 Rewiring of inner retinal
circuits are known to occur naturally
in RP making researchers believe it is
possible to create visually useful percepts by stimulating retinal ganglion
cells electrically.55 This has lead to the
development of techniques to induce
photosensitivity in cells that are not
normally light sensitive as well as the
development of what is being termed
“the bionic retina.”55 The use of
molecular engineering and nanotechnology to render cells light-sensitive
and to target ion channels in appropriate cell types (e.g., bipolar cell)
and/or cell region (e.g., dendritic tree
vs. soma) continues and offers promise where there was none before.55
Findings in some controlled trials
indicate that nutritional interventions, including vitamin A palmitate
and omega-3-rich fish, slow progression of disease in many patients.56-58
Patients having retinitis pigmentosa
placed on vitamin A therapy with
docosahexaenoic acid, 1,200mg/d,
VITREOUS AND RETINA
hemorrhage, hearing loss, dyslipidemia.) and 3) Suggest counseling to
maintain quality of life.1-53 While
the suspicion of RP is based upon
clinical appearance, there are retinopathological conditions that mimic
its distinctive retinopathy. These may
include rubella retinopathy, syphilitic
retinopathy, cytomegalovirus retinopathies, toxoplasmosis, cancer-associated
retinopathy, retinal drug toxicity secondary to thioridazine, chlorpromazine
or chloroquine, pigmented paravenous
retinochoroidal atrophy and traumatic
retinopathy.48-53
Visual field analysis and electrodiagnostic testing along with dark adaptometry should always be obtained to
confirm suspected cases.1-3,24,26,36-38
FAF can provide information regarding the integrity of the photoreceptor
layer, serving as a secondary instrument for both diagnosis and therapeutic monitoring.41,42
A pedigree can be done to determine the inheritance pattern and to
assess risk to offspring.1-4,14,15,44,46-48
Low-vision services are indicated as
the disorder affects normal visual function.5,36 Field expansion devices, infrared blocking sun lenses and contrast
enhancing filters may all be helpful.
Visual field analysis and evaluation
for cataract development or macular
edema should be performed at least
biannually.
The artificial silicon retina (ASR)
microchip is a new technology
designed to be implanted into the
subretinal space to treat vision loss.5
The ASR microchip is a 2-mm diameter silicon-based device that contains
approximately 5,000 microelectrodetipped microphotodiodes.5 It is powered by incident light.5 Visual function
improvements have been documented
in patients and included unexpected
improvements in retinal areas distant
from the implant.5 Subjective improvements included improved perception of
Peripheral “bone spicules” are the hallmark
sign of retinitis pigmentosa.
demonstrated a slowed the course of
disease over the following two-year
period.58 Lutein supplementation of
12mg/d also has shown promise for
slowing loss of midperipheral visual
field in nonsmoking adults with retinitis pigmentosa taking vitamin A.57
Supplementation therapy is not free of
controversy. As there is no universally
agreed upon regimen and the affects
of long-term use remain in question.
The literature also suggests that while
patients may experience some degree
of measurable visual preservation they
do not seem to benefit functionally
and must be closely medically monitored while on these preparations.44
Clinical Pearls
• The earliest clinical indicators
such as attenuation of the retinal arterioles, midperipheral intraneural retinal
pigment (bone spicules), perivascular
pigmentary hyperplasia, thinning and
atrophy of the RPE in the mid and
far periphery are frequently detectable
before the emergence of macular signs
or subjective symptoms.
• It is often beneficial to recommend psychological or family counseling early in the course of this disease
as the process has no cure.54,59
• Patients should be educated
regarding the need for periodic examination to reassess status as well as
manage ongoing refractive and mobility needs.
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• The potential for visual enhancement with low-vision devices and
vision rehabilitation should be
explained and explored.
1. Ferrari S, Di Iorio E, Barbaro V, et al. Retinitis
pigmentosa: genes and disease mechanisms. Curr
Genomics. 2011;12(4):238-49.
2. Sahel J, Bonnel S, Mrejen S, Paques M. Retinitis
pigmentosa and other dystrophies. Dev Ophthalmol.
2010;47:160-7.
3. Hamel C. Retinitis pigmentosa. Orphanet J Rare
Dis. 2006;1(1):40.
4. Koenekoop RK. Why do cone photoreceptors
die in rod-specific forms of retinal degenerations?
Ophthalmic Genet. 2009;30(3):152-4.
5. Chow AY, Chow VY, Packo KH, et al. The artificial
silicon retina microchip for the treatment of vision
loss from retinitis pigmentosa. Arch Ophthalmol.
2004;122(4):460-9.
6. Dufier JL. Early therapeutic trials for retinitis pigmentosa. Bull Acad Natl Med. 2003;187(9):1685-92;
discussion 1692-4.
7. Park SB, Ma KT, Kook KH, et al. Kearns-Sayre syndrome -3 case reports and review of clinical feature.
Yonsei Med J. 2004;45(4):727-35.
8. Delyfer MN, Leveillard T, Mohand-Said S, et al.
Inherited retinal degenerations: therapeutic prospects.
Biol Cell. 2004;96(4):261-9.
9. Obuchowska I, Mariak Z. New approaches towards
pathogenesis, diagnosis, natural course and complications of optic disc drusen. Klin Oczna. 2004;106(12):98-101.
10. Ali RR. Prospects for gene therapy. Novartis
Found Symp. 2004;255:165-72.
11. Koenig R. Bardet-Biedl syndrome and Usher syndrome. Dev Ophthalmol. 2003;37:126-40.
12. Bamiou DE, Spraggs PR, Gibberd FB, et
al. Hearing loss in adult Refsum’s disease. Clin
Otolaryngol. 2003;28(3):227-30.
13. Hims MM, Diager SP, Inglehearn CF. Retinitis
pigmentosa: genes, proteins and prospects. Dev
Ophthalmol. 2003;37:109-25.
14. Sahni JN, Angi M, Irigoyen C, et al. Therapeutic
challenges to retinitis pigmentosa: from neuroprotection
to gene therapy. Curr Genomics. 2011;12(4):276-84.
15. Chang S, Vaccarella L, Olatunji S, et al. Diagnostic
challenges in retinitis pigmentosa: genotypic multiplicity and phenotypic variability. Curr Genomics.
2011;12(4):267-75.
16. Yan D, Liu XZ. Genetics and pathological
mechanisms of Usher syndrome.J Hum Genet.
2010;55(6):327-35.
17. Fleischhauer J, Njoh WA, Niemeyer G. Syndromic
retinitis pigmentosa: ERG and phenotypic changes.
Klin Monbl Augenheilkd. 2005;222(3):186-90.
18. Rüether K, Baldwin E, Casteels M, et al. Adult
Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. Surv Ophthalmol.
2010;55(6):531-8.
19. Grant CA, Berson EL. Treatable forms of retinitis
pigmentosa associated with systemic neurological disorders. Int Ophthalmol Clin. 2001;41(1):103-10.
20. Sani MN, Sabbaghian M, Mahjoob F, et al.
Identification of a novel mutation of MTP gene in
a patient with abetalipoproteinemia. Ann Hepatol.
2011;10(2):221-6.
21. Lanier KT, Joy JT, Morris RW. Nonclassic retinitis
56A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 56
pigmentosa: A challenging clinical diagnosis solved
by pedigree analysis and electrodiagnostic testing.
Optometry. 2010;81(4):181-7.
22. Bittner AK, Diener-West M, Dagnelie G.
Characteristics and possible visual consequences
of photopsias as vision measures are reduced in
retinitis pigmentosa. Invest Ophthalmol Vis Sci.
2011;52(9):6370-6.
23. Jacobson SG, Roman AJ, Aleman TS, et al.
Normal central retinal function and structure preserved
in retinitis pigmentosa. Invest Ophthalmol Vis Sci.
2010;51(2):1079-85.
24. Sieving PA. Retinitis pigmentosa and related disorders. In: Yanoff M, Duker JS. Ophthalmology 2nd Ed.
Mosby, Philadelphia, 2004: 813-823.
25. Han KH, Kim JW. Electrophysiologic Finding
of Retinitis Pigmentosa Inversus and Differential
Diagnosis from Peripapillary Choroidal Dystrophy. J
Korean Ophthalmol Soc. 1996;37(2):275-283.
26. Zhang Q, Zulfiqar F, Xiao X, et al. Severe retinitis
pigmentosa mapped to 4p15 and associated with
a novel mutation in the PROM1 gene. Hum Genet.
2007;122 (3-4):293-9.
27. Yang C, Liu Y, Lu X, et al. Sporadic bilateral
retinitis pigmentosa sine pigmento associated with
atypical Peutz-Jeghers syndrome. Can J Ophthalmol.
2010;45(2):184-5.
28. Ferrucci S, Anderson SF, Townsend JC. Retinitis
pigmentosa inversa. Optom Vis Sci. 1998;75(8):560-70.
29. Thobani A, Fishman GA. The use of carbonic
anhydrase inhibitors in the retreatment of cystic macular lesions in retinitis pigmentosa and X-linked retinoschisis. Retina. 2011;31(2):312-5.
30. Giusti C, Forte R, Vingolo EM. Clinical pathogenesis of macular holes in patients affected by retinitis
pigmentosa. Eur Rev Med Pharmacol Sci. 2002;6(23):45-8.
31. Ponjavic V, Andréasson S, Abrahamson M, et al.
Clinical expression of X-linked retinitis pigmentosa in
a Swedish family with the RP2 genotype. Ophthalmic
Genet. 1998;19(4):187-96.
32. Watanabe A, Akiyama G, Tsuneoka H. A case
of retinitis pigmentosa requiring vitrectomy because
of repeated vitreous hemorrhage. Case report
Ophthalmol. 2011;2(2):256-61.
33. Hong PH, Han DP, Burke JM, Wirostko WJ.
Vitrectomy for large vitreous opacity in retinitis pigmentosa. Am J Ophthalmol. 2001;131(1):133-4.
34. Jethani J, Mishra A, Shetty S, Vijayalakshmi P.
Weill-Marchesani syndrome associated with retinitis
pigmentosa. Indian J Ophthalmol. 2007;55(2):142-3.
35. Lee SH, Yu HG, Seo JM, et al. Hereditary and
clinical features of retinitis pigmentosa in Koreans. J
Korean Med Sci. 2010;25(6):918-23.
36. Bogd nici C, Rusu C, Mo oc I, Cr maru C.
Retinitis pigmentosa--clinical and genetic aspects with
low vision. Oftalmologia. 2008;52(2):64-71.
37. Grünauer-Kloevekorn C, Duncker GI. Keratoconus:
epidemiology, risk factors and diagnosis. Klin Monbl
Augenheilkd. 2006;223(6):493-502.
38. Maiti A, Uparkar M, Natarajan S, et al. Principal
components’ analysis of multifocal electroretinogram in retinitis pigmentosa. Indian J Ophthalmol.
2011;59(5):353-7.
39. Pojda-Wilczek D. Electroretinogram and electrooculogram in retinal degeneration. Klin Oczna.
1999;101(6):481-5.
40. Kiser AK, Mladenovich D, Eshraghi F, et al.
Reliability and consistency of dark-adapted psychophysical measures in advanced eye disease. Invest
Ophthalmol Vis Sci. 2006;47(1):444-52.
41. Chen RW, Greenberg JP, Lazow MA, et al.
Autofluorescence imaging and spectral-domain optical coherence tomography in incomplete congenital
stationary night blindness and comparison with retinitis pigmentosa. Am J Ophthalmol. 2012;153(1):143154.
42. Liu Y, Liu DN, Meng XH, Yin ZQ. Transient pupillary light reflex in relation to fundus autofluorescence
and dark-adapted perimetry in typical retinitis pigmentosa. Ophthalmic Res. 2011;47(3):113-121.
43. Wakabayashi T, Sawa M, Gomi F, Tsujikawa
M. Correlation of fundus autofluorescence with
photoreceptor morphology and functional changes
in eyes with retinitis pigmentosa. Acta Ophthalmol.
2010;88(5):177-83.
44. Shintani K, Shechtman DL, Gurwood AS. Review
and update: current treatment trends for patients with
retinitis pigmentosa. Optometry. 2009;80(7):384-401.
45. Cottet S, Schorderet DF. Mechanisms of
apoptosis in retinitis pigmentosa. Curr Mol Med.
2009;9(3):375-83.
46. Clark GR, Crowe P, Muszynska D, et al.
Development of a diagnostic genetic test for simplex and autosomal recessive retinitis pigmentosa.
Ophthalmology. 2010;117(11):2169-77.
47. Jin ZB, Mandai M, Yokota T, et al. Identifying
pathogenic genetic background of simplex or multiplex
retinitis pigmentosa patients: a large scale mutation
screening study. J Med Genet. 2008;45(7):465-72.
48. Richa S, Yazbek JC. Ocular adverse effects of
common psychotropic agents: a review. CNS Drugs.
2010;24(6):501-26.
49. Vasconcelos-Santos DV, Dodds EM, Oréfice F.
Review for disease of the year: differential diagnosis
of ocular toxoplasmosis. Ocul Immunol Inflamm.
2011;19(3):171-9.
50. Zambon F, Silva FL, Cavalcante AF, et al. Syphilitic
retinitis and panuveitis simulating acute retinal necrosis:
case report. Arq Bras Oftalmol. 2010;73(3):288-90.
51. Shields JA, Shields CL, Shah PG, et al. Lack of
association among typical congenital hypertrophy
of the retinal pigment epithelium, adenomatous
polyposis, and Gardner syndrome. Ophthalmology.
1992;99(11):1709-13.
52. Cymerys E, Pecold K, Paszkowski J, et al. Retinal
changes in patients with familial adenomatous polyposis. Klin Oczna. 2006;108(1-3):70-2.
53. Zamel R, Khan R, Pollex RL, Hegele RA.
Abetalipoproteinemia: two case reports and literature
review. Orphanet J Rare Dis. 2008;3(7):19.
54. Sahni JN, Angi M, Irigoyen C, et al. Therapeutic
challenges to retinitis pigmentosa: from neuroprotection
to gene therapy. Curr Genomics. 2011;12(4):276-84.
55. Zarbin M, Montemagno C, Leary J, Ritch R.
Artificial vision. Panminerva Med. 2011;53(3):167-77.
56. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795-809.
57. Berson EL, Rosner B, Sandberg MA, et al.
Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol.
2010;128(4):403-11.
58. Berson E, Rosner B, Sandberg M, et al. Further
evaluation of DHA in patients with RP receiving vitamin
A treatment. Arch Ophthalmol 2004;122(9):1306-14.
59. Chang TG, Wang CH, Chiu NY, Hsu WY.
Application of electroconvulsive therapy in treatment of retinitis pigmentosa comorbid with major
depressive disorder and panic disorder. J ECT.
2011;27(4):57-8.
JUNE 15, 2012
6/1/12 3:32 PM
NEURO-OPHTHALMIC DISEASE
Signs and Symptoms
The patient with arteritic anterior
ischemic optic neuropathy (AAION)
will typically be elderly (with an average age of 75 years), more commonly
female, Caucasian, and will present
with a loss of vision and visual field.1-3
The visual loss is typically profound.1-3
Visual acuity may initially, in rare
instances, be quite good; however, acuity usually deteriorates quickly into the
range of of 20/200 to no light perception.3 While the vision loss is typically
not accompanied by frank eye pain,
the patient will frequently complain of
scalp pain, headache, and jaw claudication.1-5 The vision loss is typically unilateral, but may be bilateral or rapidly
sequential.3 The field defect in testable
eyes includes central scotomas associated with acuity loss, as well as altitudinal
or arcuate patterns.3 Unless the case is
bilateral, an afferent pupil defect will be
present. Visual loss may be rapidly progressive over several days.3,6,7 Patients
may recount several occurrences of
amaurosis fugax or intermittent diplopia and ophthalmoparesis preceding
the onset of the AAION.8
Patients with AAION will usually
present with a prodrome of anorexia,
weight loss, decreased appetite (all
due to discomfort while eating from
jaw claudication), fever and malaise.4,9
There will be a relative afferent papillary defect and dyschromatopsia.
Funduscopically, the involved optic
disc will be swollen, edematous, pale
and atrophic, often with associated
splinter hemorrhages.1,4 The disc
edema is often described as “chalky
white.” After the initial ischemic event,
the disc will undergo a glaucoma-like
optic disc degeneration with cupping,
though there will often be pallor of the
remaining neuroretinal rim.10,11
NEURO-OPHTHALMIC DISEASE
ARTERITIC ANTERIOR
ISCHEMIC OPTIC
NEUROPATHY
Patients experiencing AAION typically have rheumatologic disease, often
manifested by polymyalgia rheumatica.
Typically, following the event of acute
vision loss, the patient will test positively for giant cell arteritis (GCA).12
Pathophysiology
Arteritic anterior ischemic optic
neuropathy is caused by infarction
of the short posterior ciliary arteries
supplying the anterior optic nerve.
Fluorescein angiography and color
Doppler imaging readily demonstrate
non-filling of the posterior ciliary
arteries and significant delay in choroidal filling times.13-15 These vessels,
as well as the ophthalmic and portions of the central retinal arteries,
are compromised by an infiltration
of the vessels’ walls by inflammatory
macrophages, lymphocytes and multinucleate giant cells. As most arteries
are affected in GCA, there usually is
an attendant constellation of systemic
symptoms. Due to the widespread
vascular involvement in GCA, there
is a propensity for the fellow eye to
become similarly involved, often quite
rapidly, with severe bilateral vision
loss ensuing.16-19
Patients with GCA and AAION
have been found to have serologic
abnormalities that not only may contribute to the development of AAION,
but also may prove useful diagnostically.
A strong association between IgG anticardiolipin antibodies and AAION secondary to biopsy-proven giant cell arteritis has been identified.20,21 An elevated
level of IgG anticardiolipin antibodies
may be a risk factor to thrombotic complications, such as AAION, in patients
with GCA.20,21 Elevated platelet count
is often seen in patients with GCA and
AAION. Thrombocytosis is considered
to be especially predictive of vision loss
and the excess platelets may lead to
thrombosis.22-24 Often, plasma viscosity
is elevated and may reflect a more spe-
Pale disc edema in arteritic anterior ischemic
optic neuropathy.
cific component of the acute inflammatory response.25
Management
Elderly patients with unilateral sudden vision loss and a pale edematous
optic disc should be presumed to have
ischemic optic neuropathy. The history should be probed for the concurrent ocular and systemic symptoms to
determine if the patient has GCA and
AAION. A Westergren erythrocyte
sedimentation rate (ESR) should be
ordered immediately for these patients.
In most AAION cases, this will be
grossly elevated. It must be noted
that 15% of patients with GCA will
have a normal ESR.26 Thus, a normal
ESR does not preclude the diagnosis
of AAION, especially in the presence
of constitutional symptoms suggestive of GCA. Elevated white blood
cell and platelet count, as well as IgG
anticardiolipin antibodies, may also
be diagnostic.20-24 C-Reactive protein
(CRP) is also elevated in patients with
AAION secondary to GCA and is
now considered a mandatory test in
the diagnosis of patients with GCArelated complications.22,24-27 In fact,
the CRP may be a better diagnostic
marker of GCA-related AAION than
the ESR. However, like a normal ESR,
it is possible to have a normal CRP in
a patient suffering from GCA. The
finding of an elevated ESR and a normal CRP is consistent with GCA.28 At
a minimum, patients with presumed
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001_ro0612_hndbk.indd 57
57A
6/1/12 3:32 PM
AAION must be evaluated with ESR,
CRP, and complete blood count with
differential on an emergency basis.
Should the diagnostic evaluation
(elevated ESR & CRP, thrombocytosis, increased plasma viscosity, etc.)
and/or clinical presentation (systemic
signs and symptoms of GCA) indicate
AAION, then a temporal artery biopsy
must be performed to examine for the
presence of inflammatory cells in the
muscular walls of the artery.29-31 If the
patient is either suspected to have, or
diagnosed with, AAION, then systemic steroids must be initiated immediately in order to prevent vision loss
progressing to the other eye.4,27,31-33
Steroid therapy should not be withheld
pending the biopsy. The treatment
can be initiated in suspicious cases
before the biopsy while awaiting the
results. The dosage and route of steroid
administration cannot been scientifically determined through controlled studies due to the high morbidity of this
disease. However, anecdotal evidence
suggests that the best known current
therapy involves hospital admission
with 1g-2g IV methylprednisolone for
two to three days, followed by chronic
use of oral steroids (60mg to 100mg
q.d. of prednisone).32-40 This aggressive
therapy has been shown to have the
best outcome in regards to preservation
of existing vision and well as rare visual
recovery of involved eyes.
While the vision loss associated with
AAION is typically devastating and
considered irreversible even with prompt
treatment, there have been anecdotal
reports of visual recovery, often associated with IV steroid use.32-36 Oral
steroids are tapered and maintained for
prolonged periods; an increase in systemic symptoms is not a reliable indicator of disease reactivation.35 In spite of
aggressive therapy, GCA-related vision
loss has been seen to frequently progress
to the fellow eye, giving this disease a
guarded prognosis.16
58A REVI EW OF OPTOME TRY
001_ro0612_hndbk.indd 58
There have been attempts to
identify non-steroidal therapies for
patients with manifestations of GCA.
Methotrexate and azathioprine have
been used as steroid-sparing agents
based on anecdotal evidence. More
recently, evidence is emerging that
antitumor necrosis factor-alpha may
be efficacious.41 However, success
with medications other than steroids
is merely anecdotal. A controlled
study looking at methotrexate as an
adjunctive therapy along with steroids
did not demonstrate any benefits.42
It has been noted that antiplatelet
or anticoagulant therapy may reduce
the risk of ischemic events in patients
with GCA. Low-dose aspirin has
been shown in studies to decrease
the rate of cranial ischemic complications secondary to giant cell arteritis
and decreases the rate of visual loss
and cerebrovascular accidents. Low
dose aspirin therapy has been recommended as an adjunct to steroids in
the management of patients with
GCA.43-49
Clinical Pearls
• Any patient over the age of 60
years with sudden unilateral vision loss
and a pale edematous disc must be
considered to have GCA and AAION.
• The pallor in AAION has been
described as chalky white.
• This is a true emergency, and
warrants immediate consultation with
a physician (typically a neurologist or
neuro-ophthalmologist) specifically
skilled in the management of GCA
and AAION. Further, any elderly
patient presenting with headache, head
pain or, especially, amaurosis fugax
must be evaluated for GCA.
• Central retinal artery occlusion
(CRAO), while usually caused by
embolism, occurs due to GCA in 2%
to 10% of cases. Any patient in the
proper demographic over the age of
65 years presenting with CRAO must
be assumed to have GCA until proven
otherwise. Single or multiple cotton
wool spots in this demographic should
also be considered as possible signs of
GCA.
• Though visual recovery has
occurred in patients with AAION
(typically with high dose steroid
therapy), do not expect improvement.
Instead, direct efforts at preserving the
existing level of vision in the involved
as well as fellow eye.
1. Hayreh SS. Ischaemic optic neuropathy. Indian J
Ophthalmol. 2000;48(3):171-94.
2. Gonzalez-Gay MA, Garcia-Porrua C, Llorca J, et al.
Visual manifestations of giant cell arteritis. Trends and
clinical spectrum in 161 patients. Medicine (Baltimore).
2000;79(5):283-92.
3. Liu GT, Glaser JS, Schatz NJ, et al. Visual morbidity
in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology. 1994;101(11):1779-85.
4. Wilk A, Kazimierczuk K. Optic nerve neuropathy in the course of giant cell arteritis. Klin Oczna.
2003;105(3-4):217-20.
5. McFadzean RM. Ischemic optic neuropathy and giant
cell arteritis. Curr Opin Ophthalmol. 1998;9(6):10-7.
6. Goh KY, Lim TH. Giant cell arteritis causing bilateral
sequential anterior ischaemic optic neuropathy--a case
report. Singapore Med J. 2000;41(1):32-3.
7. Fathilah J, Jamaliah R. Giant cell arteritis with panocular involvement in an Indian male. Med J Malaysia.
2003;58(1):111-4.
8. Hayreh SS, Podhajsky PA, Zimmerman B. Ocular
manifestations of giant cell arteritis. Am J Ophthalmol.
1998;125(4):509-20.
9. Gonzalez-Gay MA, Garcia-Porrua C, Amor-Dorado
JC, et al. Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population. Arthritis Rheum.
2004;51(4):652-5.
10. Hayreh SS, Jonas JB. Optic disc morphology
after arteritic anterior ischemic optic neuropathy.
Ophthalmology. 2001;108(9):1586-94.
11. Danesh-Meyer HV, Savino PJ, Sergott RC. The
prevalence of cupping in end-stage arteritic and
nonarteritic anterior ischemic optic neuropathy.
Ophthalmology. 2001;108(3):593-8.
12. Gonzalez-Gay MA. Giant cell arteritis and polymyalgia rheumatica: two different but often overlapping conditions. Semin Arthritis Rheum. 2004;33(5):289-93.
13. Valmaggia C, Speiser P, Bischoff P, et al.
Indocyanine green versus fluorescein angiography in the
differential diagnosis of arteritic and nonarteritic anterior
ischemic optic neuropathy. Retina. 1999;19(2):131-4.
14. Siatkowski RM, Gass JD, Glaser JS, et al.
Fluorescein angiography in the diagnosis of giant cell
arteritis. Am J Ophthalmol. 1993;115(1):57-63.
15. Ghanchi FD, Williamson TH, Lim CS, et al. Colour
Doppler imaging in giant cell (temporal) arteritis: serial
examination and comparison with non-arteritic anterior
ischaemic optic neuropathy. Eye. 1996;10 ( Pt 4):45964.
16. Zborowska B, Ell J, McGhee-Collett M, et al.
Progressive visual loss in a patient with presumed temporal arteritis despite treatment: how to make the diagnosis. Clin Experiment Ophthalmol. 2004;32(3):335-6.
JUNE 15, 2012
6/1/12 3:32 PM
NON-ARTERITIC ANTERIOR
ISCHEMIC OPTIC
NEUROPATHY
Signs and Symptoms
Non-arteritic anterior ischemic
optic neuropathy (NAAION) typically presents as a painless, unilateral
disturbance of vision. Patients are older
but not necessarily elderly, generally
in the 55- to 65-year-old age group.
The onset of NAAION may occur
as early as the late 30s and early 40s.1
Men and women are affected equally,
although there are racial disparities,
with the disease being most prevalent
in Caucasians.1,2 Many patients with
NAAION have some underlying systemic disease, although they may not
be aware of any health problems at
the time of presentation. Most often,
vascular disorders such as hypertension,
diabetes, and/or atherosclerosis are
present. It has also been demonstrated
Hyperemic disc edema in a case of non-arteritic
anterior ischemic optic neuropathy.
that elevated plasma homocysteine
and lipoprotein(a) levels, as well as low
vitamin B6 levels, may increase the risk
of developing NAAION.3
In contrast to the arteritic variety,
vision loss in NAAION tends to occur
gradually. While some patients report
a rapid decline in acuity over several
days, 45% of cases present with a history of vision loss that worsens over
two weeks, with another 29% reporting
progression of the visual deterioration over 30 days.4 Visual acuity may
be moderate to poor; about half of
patients present with 20/60 or better, while roughly a third have entering acuity of less than 20/200.2 It is
exceedingly rare to encounter no light
perception (NLP) vision in patients
with NAAION. Visual field defects
most commonly include inferior altitudinal, inferior arcuate, inferior nasal
and cecocentral scotomas.1
Examination of these patients
reveals a relative afferent pupil defect
(RAPD) in the involved eye. There
is generally little pain or other associated symptoms, a feature that helps to
distinguish this condition from other
optic neuropathies. Ophthalmoscopy
reveals disc edema, which may be
diffuse or segmental.1,5 Disc hemorrhages are common, occurring in
more than two-thirds of patients with
NAAION.1 In addition, the optic disc
is characteristically hyperemic, often
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001_ro0612_hndbk.indd 59
NEURO-OPHTHALMIC DISEASE
matica and giant cell arteritis in older patients: diagnosis
and pharmacological management. Drugs Aging.
2011;28(8):651-66.
41. Ward TN, Levin M, Wong RL. Headache caused
by Giant Cell Arteritis. Curr Treat Options Neurol.
2004;6(6):499-505.
42. Hoffman GS, Cid MC, Hellmann DB, et al.;
International Network for the Study of Systemic
Vasculitides. A multicenter, randomized, doubleblind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum.
2002;46(5):1309-18.
43. Lee MS, Smith SD, Galor A, Hoffman GS.
Antiplatelet and anticoagulant therapy in patients with
giant cell arteritis. Arthritis Rheum. 2006;54(10):3306-9.
44. Fraser JA, Weyand CM, Newman NJ, Biousse V.
The treatment of giant cell arteritis. Rev Neurol Dis. 2008
Summer;5(3):140-52.
45. Pipitone N, Salvarani C. Improving therapeutic
options for patients with giant cell arteritis. Curr Opin
Rheumatol. 2008;20(1):17-22.
46. Pipitone N, Boiardi L, Salvarani C. Are steroids alone
sufficient for the treatment of giant cell arteritis? Best
Pract Res Clin Rheumatol. 2005;19(2):277-92.
47. Schmidt WA. Current diagnosis and treatment of
temporal arteritis. Curr Treat Options Cardiovasc Med.
2006;8(2):145-51.
48. Øverlie H, Kerty E. Temporal arteritis and cerebrovascular complications. Tidsskr Nor Laegeforen. 2005
3;125(21):2936-8.
49. Nesher G, Berkun Y, Mates M, et al. Low-dose aspirin and prevention of cranial ischemic complications in
giant cell arteritis. Arthritis Rheum. 2004;50(4):1332-7.
Image courtesy of Dr. Andy White
17. Chan CC, Paine M, O’Day J. Steroid management in
giant cell arteritis. Br J Ophthalmol. 2001;85(9):1061-4.
18. Machova L, Pavelka K, Kubena T, et al. Clinical
features and therapy of giant cell temporal arteritis.Cesk
Slov Oftalmol. 2001;57(1):33-7.
19. Liu GT, Glaser JS, Schatz NJ, et al. Visual morbidity
in giant cell arteritis. Clinical characteristics and prognosis
for vision. Ophthalmology. 1994;101(11):1779-85.
20. Watts MT, Greaves M, Rennie IG, et al.
Antiphospholipid antibodies in the aetiology of ischaemic
optic neuropathy. Eye. 1991;5(Pt 1):75-9.
21. Ezpeleta D, Rodriguez-Mahou M, Munoz-Blanco
JL. Giant cell arteritis, bilateral anterior ischemic optic
neuropathy and anticardiolipin antibodies. Rev Neurol.
1999;29(12):1185-7.
22. Costello F, Zimmerman MB, Podhajsky PA, et
al. Role of thrombocytosis in diagnosis of giant cell
arteritis and differentiation of arteritic from non-arteritic
anterior ischemic optic neuropathy. Eur J Ophthalmol.
2004;14(3):245-57.
23. Lincoff NS, Erlich PD, Brass LS. Thrombocytosis in
temporal arteritis rising platelet counts: a red flag for giant
cell arteritis. J Neuroophthalmol. 2000;20(2):67-72.
24. Liozon E, Herrmann F, Ly K, et al. Risk factors for
visual loss in giant cell (temporal) arteritis: a prospective
study of 174 patients. Am J Med. 2001;111(3):211-7.
25. Finke C, Schroeter J, Kalus U, Ploner CJ. Plasma viscosity in giant cell arteritis. Eur Neurol. 2011;66(3):159-64.
26. von Blotzeim SG, Borruat FX. Giant cell arteritis and
normal sedimentation rate: more than an exception! Klin
Monatsbl Augenheilkd. 1996;208(5):397-9.
27. Hayreh SS, Podhajsky PA, Zimmerman B.
Occult giant cell arteritis: ocular manifestations. Am J
Ophthalmol. 1998;125(4):521-6.
28. Parikh M, Miller NR, Lee AG, et al. Prevalence of a
normal C-reactive protein with an elevated erythrocyte
sedimentation rate in biopsy-proven giant cell arteritis.
Ophthalmology. 2006;113(10):1842-5.
29. Lichtstein DM, Caceres LR. Heeding clues to giant
cell arteritis. Prompt response can prevent vision loss.
Postgrad Med. 2004;115(5):91-5.
30. Hall JK, Volpe NJ, Galetta SL, Liu GT, et al. The
role of unilateral temporal artery biopsy. Ophthalmology.
2003;110(3):543-8.
31. Diamond JP.Treatable blindness in temporal arteritis.
Br J Ophthalmol. 1991;75(7):432.
32. Hayreh SS, Zimmerman B, Kardon RH. Visual
improvement with corticosteroid therapy in giant cell
arteritis. Report of a large study and review of literature.
Acta Ophthalmol Scand. 2002;80(4):355-67.
33. Chan CC, Paine M, O’Day J. Steroid management in
giant cell arteritis. Br J Ophthalmol. 2001;85(9):1061-4.
34. Foroozan R, Deramo VA, Buono LM, et al. Recovery
of visual function in patients with biopsy-proven giant cell
arteritis. Ophthalmology. 2003;110(3):539-42.
35. Postel EA, Pollock SC. Recovery of vision in a
47-year-old man with fulminant giant cell arteritis. J Clin
Neuroophthalmol. 1993;13(4):262-70.
36. Kim N, Trobe JD, Flint A, et al. Late ipsilateral recurrence of ischemic optic neuropathy in giant cell arteritis. J
Neuroophthalmol. 2003;23(2):122-6.
37. Hayreh SS. Management of ischemic optic neuropathies. Indian J Ophthalmol. 2011;59(2):123-36.
38. Scheurer RA, Harrison AR, Lee MS. Treatment of
Vision Loss in Giant Cell Arteritis. Curr Treat Options
Neurol. 2011 Oct 27. [Epub ahead of print].
39. Gonzalez-Gay MA, Martinez-Dubois C, Agudo M, et
al. Giant cell arteritis: epidemiology, diagnosis, and management. Curr Rheumatol Rep. 2010;12(6):436-42.
40. Schmidt J, Warrington KJ. Polymyalgia rheu-
59A
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displaying dilation of the overlying
arterioles (which is sometimes erroneously diagnosed as neovascularization).
The retinal veins are typically dilated
and tortuous. Significant concurrent
retinopathy may be present, depending upon the severity of the patient’s
underlying systemic condition.
Finally, a key diagnostic characteristic of NAAION involves a small,
crowded optic disc with minimal
cupping in the contralateral eye. This
“disc at risk,” as some have called it, is
recognized as a significant risk factor
for the development of NAAION in
predisposed individuals.1,6,7
Pathophysiology
NAAION represents an infarction
of the anterior portion of the optic
nerve, typically involving the paraoptic
branches of the short posterior ciliary
arteries.7,8 By definition, this infarction
occurs in the absence of inflammation,
demyelination or compression.9 The
vasculopathic etiology is usually hypertension or diabetes, both of which are
often accompanied by arteriosclerosis.
According to one report, diabetes is
the most consistently identified vasculopathic risk factor in NAAION.6
Genetic factors and smoking may also
play a role.10,11
Hayreh and others have proposed
that NAAION results from dysfunctional vascular autoregulatory
mechanisms at the level of the optic
nerve.8,12-14 This may occur as a result
of transient nocturnal arterial hypotension, overtreatment for systemic
hypertension, or simply because of the
“crowding” of neurons within the optic
disc of these patients and associated
poor perfusion. Optic disc drusen have
also been identified as a potential causative factor, although this may simply
represent coincidental pathology in
congenitally small optic discs.15
There have been numerous
reports of vision loss presumed from
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001_ro0612_hndbk.indd 60
NAAION in patients using phosphodiesterase type-5 (PDE-5) inhibitors for the management of erectile
dysfunction.16-20 However, these
reports which have suggested a relationship between PDE-5 inhibitor
use and NAAION are case reports
and small series observations without
adequate controls or monitoring of
co-variables. Additionally, the small
number of cases compared against
the widespread use of these medications makes it difficult to conclude a
causal relationship. Still, it is recommended that men experiencing any
form of vision loss while using these
medications stop their use immediately and seek medical attention.
Further, it is recommended that
patients be made aware of this possible adverse event prior to using the
medications. It is felt that men with
a history of myocardial infarction or
hypertension have a greater risk of
experiencing NAAION while using
these medications.17
Cataract surgery is a known risk for
developing NAAION. Furthermore,
patients with unilateral NAAION are
at a significantly higher risk of developing NAAION in the fellow eye after
cataract extraction.21 This also should
be a consideration when planning
fellow-eye surgery.
Management
Appropriate management for
NAAION begins with making the
correct diagnosis. NAAION must
be differentiated from demyelinating optic neuropathy, which tends to
present abruptly in younger patients,
and arteritic anterior ischemic optic
neuropathy (AAION), which tends to
present apoplectically in older patients.
While there are no specific laboratory
studies that can confirm a diagnosis of
NAAION, an erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) should be ordered for any
older patient in whom the diagnosis
is uncertain. Taken together, the ESR
and CRP have a specificity of 97% for
giant cell arteritis, the primary etiology
of AAION.22 Likewise, MRI of the
brain, chiasm, and optic nerve should
be performed on any younger patients
with this differential diagnosis to rule
out paraventricular white matter lesions
that may be seen in multiple sclerosis.
The prognosis for NAAION is
guarded, but better than the prognosis seen in AAION. In general,
visual acuity improves by three or
more lines in 43% of patients at six
months.3 Involvement of the fellow eye
occurs just 18% of the time, and may
take three years to occur.3 Recurrent
NAAION in the same eye is rare,
occurring in less than 5% of cases.23,24
There is no specific, universally
accepted treatment for NAAION.
NAAION eyes can spontaneously
recover some visual function. Optic
nerve sheath fenestration was investigated in the early 1990’s, but abandoned as a therapy because of poor
efficacy and high risk.25 Likewise, a
study published in 2000 suggested that
treatment with levodopa may be beneficial for patients with NAAION26, but
numerous articles have since refuted
this research and therapy.27,28 Even
daily aspirin therapy has been recommended as prophylactic therapy, but
the five-year cumulative benefit was
shown to be less than 3%.29
Recently, intravitreal injections of
ranibizumab and erythropoietin individually have been noted to increase
visual function in eyes with NAAION,
but again these were very small, uncontrolled cases.30,31 Intravitreal injection
of triamcinolone acetonide (IVTA)
likewise has been seen to improve visual function in eyes with NAAION.32-34
Most of these were case reports with
no control group. Larger, controlled
studies are needed before intravitrealinjected triamcinolone acetonide can
JUNE 15, 2012
6/1/12 3:32 PM
Clinical Pearls
• Dr. Larry Gray described the
detection of NAAION as “diagnosing in the negative.” Essentially, this
means that we arrive at a diagnosis of NAAION by eliminating all
other possible neuropathies. Rule out
AAION and demyelinating disease
first, followed by infectious, inflammatory, infiltrative, and compressive
etiologies. Most of these other conditions have a specific therapy that may
help restore vision or prevent further
vision loss. No such therapy exists for
NAAION.
• Systemic corticosteroids, while a
mainstay of therapy for AAION and
other optic neuropathies, are apparently of no benefit in NAAION.
• Current research on neuroprotective agents (e.g., memantine) has
shown some benefit in treating animal
models of ischemic optic neuropathy.38 Human trials with agents such
as brimonidine unfortunately have
not shown efficacy in the treatment of
NAAION.39,40
1. Gray LG. NAION: Diagnosing in the negative. Rev
Optom. 2000;137(6):83-98.
2. Johnson LN, Arnold AC. Incidence of nonarteritic and
arteritic anterior ischemic optic neuropathy. Populationbased study in the state of Missouri and Los Angeles
County, California. J Neuroophthalmol. 1994;14(1):3844.
3. Giambene B, Sodi A, Sofi F, et al. Evaluation of
traditional and emerging cardiovascular risk factors in
patients with non-arteritic anterior ischemic optic neuropathy: a case-control study. Graefes Arch Clin Exp
Ophthalmol. 2009;247(5):693-7.
4. Ischemic Optic Neuropathy Decompression Trial
Study Group. Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the
ischemic optic neuropathy decompression trial. Arch
Ophthalmol 1996;114(11):1366-74.
5. Hayreh SS. Anterior ischemic optic neuropathy.
Differentiation of arteritic from non-arteritic type and its
management. Eye 1990;4(Part 1):25-41.
6. Burde RM. Optic disc risk factors for nonarteritic
ischemic optic neuropathy. Am J Ophthalmol. 1993;
116(6):759-64.
7. Arnold AC. Pathogenesis of nonarteritic anterior
ischemic optic neuropathy. J Neuroophthalmol. 2003;
23(2):157-63.
8. Collignon-Robe NJ, Feke GT, Rizzo JF. Optic
nerve head circulation in nonarteritic anterior ischemic
optic neuropathy and optic neuritis. Ophthalmology.
2004;111(9):1663-72.
9. Hayreh SS: Anterior ischemic optic neuropathy. Arch
Neurol. 1981;38(11):675-8.
10. Johnson LN, Kuo HC, Arnold AC. HLA-A29 as a
potential risk factor for nonarteritic anterior ischemic optic
neuropathy. Am J Ophthalmol. 1993:115(4):540-2.
11. Salomon O, Rosenberg N, Steinberg DM, et al.
Nonarteritic anterior ischemic optic neuropathy is associated with a specific platelet polymorphism located on
the glycoprotein Ibalpha gene. Ophthalmology. 2004;
111(1):184-8.
12. Chung SM, Gay CA, McCrary III JA. Nonarteritic
ischemic optic neuropathy. The impact of tobacco use.
Ophthalmology. 1994;101(4):779-82.
13. Hayreh SS, Zimmerman MB, Podhasjsky P, Alward
WL. Nocturnal arterial hypotension and its role in
optic nerve head and ocular ischemic disorders. Am J
Ophthalmol. 1994;117(5):603-24.
14. Hayreh SS. Ischaemic optic neuropathy. Indian J
Ophthalmol. 2000;48(3):171-94.
15. Purvin V, King R, Kawasaki A, Yee R. Anterior ischemic optic neuropathy in eyes with optic disc drusen.
Arch Ophthalmol. 2004;122(1):48-53.
16. Thurtell MJ, Tomsak RL. Nonarteritic anterior ischemic optic neuropathy with PDE-5 inhibitors for erectile
dysfunction. Int J Impot Res. 2008;20(6):537-43.
17. McGwin G Jr, Vaphiades MS, Hall TA, Owsley C.
Non-arteritic anterior ischaemic optic neuropathy and
the treatment of erectile dysfunction. Br J Ophthalmol.
2006;90(2):154-7.
18. Bella AJ, Brant WO, Lue TF, Brock GB. Nonarteritic anterior ischemic optic neuropathy (NAION)
and phosphodiesterase type-5 inhibitors. Can J Urol.
2006;13(5):3233-8.
19. Carter JE. Anterior ischemic optic neuropathy and
stroke with use of PDE-5 inhibitors for erectile dysfunction: cause or coincidence? J Neurol Sci. 2007;262(12):89-97.
20. Laties AM. Vision disorders and phosphodiesterase
type 5 inhibitors: a review of the evidence to date. Drug
Saf. 2009;32(1):1-18.
21. Lam BL, Jabaly-Habib H, Al-Sheikh N, et al. Risk
of non-arteritic anterior ischaemic optic neuropathy
(NAION) after cataract extraction in the fellow eye of
patients with prior unilateral NAION. Br J Ophthalmol.
2007;91(5):585-7.
22. Hayreh SS, Podhajsky PA, Raman R, Zimmerman B.
Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997;123(3):285-96.
23. Borchert M, Lessell S. Progressive and recurrent
nonarteritic anterior ischemic optic neuropathy. Am J
Ophthalmol. 1998;106(4):443-9.
24. Hayreh SS, Podhajsky PA, Zimmerman B. Ipsilateral
recurrence of nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2001;132(5):734-42.
25. The Ischemic Optic Neuropathy Decompression
Trial Research Group. Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy
(NAION) is not effective and may be harmful. JAMA
1995;273(8):625-32.
26. Johnson LN, Guy ME, Krohel GB, et al. Levodopa
may improve vision loss in recent-onset, nonarteritic
anterior ischemic optic neuropathy. Ophthalmology.
2000;107(3):521-6.
27. Beck RW. Does levodopa improve visual function in
NAION? Ophthalmology. 2000;107(8):1431-4; discussion 1435-8.
28. Hayreh SS. Does levodopa improve visual function in
NAION? Ophthalmology 2000;107(8):1434-8.
29. Beck RW, Hayreh SS, Podhajsky PA, et al. Aspirin
therapy in nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1997;123(2):212-7.
30. Bajin MS, Selver OB, Taskin O, et al. Single intravitreal ranibizumab injection in eyes with acute non-arteritic
anterior ischaemic optic neuropathy. Clin Exp Optom.
2011;94(4):367-70.
31. Modarres M, Falavarjani KG, Nazari H, et al.
Intravitreal erythropoietin injection for the treatment of
non-arteritic anterior ischaemic optic neuropathy. Br J
Ophthalmol. 2011;95(7):992-5.
32. Yaman A, Selver OB, Saatci AO, Soylev MF.
Intravitreal triamcinolone acetonide injection for acute
non-arteritic anterior ischaemic optic neuropathy. Clin
Exp Optom. 2008;91(6):561-4.
33. Jonas JB, Spandau UH, Harder B, Sauder G.
Intravitreal triamcinolone acetonide for treatment of acute
nonarteritic anterior ischemic optic neuropathy. Graefes
Arch Clin Exp Ophthalmol. 2007;245(5):749-50.
34. Sohn BJ, Chun BY, Kwon JY. The effect of an
intravitreal triamcinolone acetonide injection for acute
nonarteritic anterior ischemic optic neuropathy. Korean J
Ophthalmol. 2009;23(1):59-61.
35. Kaderli B, Avci R, Yucel A, et al. Intravitreal triamcinolone improves recovery of visual acuity in nonarteritic
anterior ischemic optic neuropathy. J Neuroophthalmol.
2007;27(3):164-8.
36. Atkins EJ, Bruce BB, Newman NJ, Biousse V.
Treatment of nonarteritic anterior ischemic optic neuropathy. Surv Ophthalmol. 2010;55(1):47-63.
37. Kerr NM, Chew SS, Danesh-Meyer HV. Non-arteritic
anterior ischaemic optic neuropathy: a review and
update. J Clin Neurosci. 2009 Aug;16(8):994-1000.
38. Kim TW, Kim DM, Park KH, Kim H. Neuroprotective
effect of memantine in a rabbit model of optic nerve
ischemia. Korean J Ophthalmol. 2002;16(1):1-7.
39. Fazzone HE, Kupersmith MJ Leibmann J.
Does topical brimonidine tartrate help NAION? Br J
Ophthalmology. 2003;87(9):1193-4.
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001_ro0612_hndbk.indd 61
NEURO-OPHTHALMIC DISEASE
be considered an effective therapy.
One study comparing four eyes of four
patients treated with 4mg of intravitreal triamcinolone acetonide against six
NAAION eyes receiving no treatment
found that IVTA provided relatively
improved recovery of visual acuity and
relatively rapid resolution of optic disc
swelling, but it did not provide visual
field improvement.35 Based upon these
results, the researchers felt a larger,
controlled clinical trial was warranted
before making a conclusion and recommendation.
Effectively, there is no specific treatment available for NAAION.36,37 The
only recommendations are to aggressively manage the predisposing and
precipitating factors. This means better
control of blood sugar, blood pressure,
cholesterol levels, and smoking cessation for all patients with NAAION.
Those with severe vision loss may benefit from a low-vision consultation.
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40. Wilhelm B, Lüdtke H, Wilhelm H; BRAION Study
Group. Efficacy and tolerability of 0.2% brimonidine
tartrate for the treatment of acute non-arteritic anterior
ischemic optic neuropathy (NAION): a 3-month, doublemasked, randomised, placebo-controlled trial. Graefes
Arch Clin Exp Ophthalmol. 2006;244(5):551-8.
BENIGN EPISODIC PUPILLARY
MYDRIASIS
Signs and Symptoms
The patient experiencing benign
pupillary mydriasis is typically female,
though this has occurred in males as
well to a much lesser degree. Also,
the patient is younger, with a typical
occurrence between the ages of 20 and
40 years.1-6 There may be a concurrent
medical history of migraine headache,
but otherwise the patient is systemically well.7,8 There has been an isolated
report of a patient with unilateral
mydriasis as well as other focal neurologic abnormalities including loss of
smell and associated pleocytosis (cells
in the cerebrospinal fluid), all of which
resolved within several days.9
The condition is defined by unilateral dilation of the pupil. Rarely is the
condition bilateral.10 The anisocoria
may be quite marked with several millimeters of size difference between
the involved pupil and the pupil in
the fellow eye. The anisocoria is often
greater in bright illumination. The
pupil will react, albeit sluggishly, to
light and near stimuli. The dilation is
transient, lasting minutes to weeks.16 Often, the patient will be isocoric
in the office, but present a history of
transient pupil dilation. The event is
unilateral and there is a concurrent
blurring of vision, especially at near. If
tested, there will be a dysfunction of
the patient’s ipsilateral accommodation
during an episode of mydriasis. There
will often be an ipsilateral headache,
which may be either dull or throbbing,
but not debilitating and not typical of
migraine. There will be no associated
lid or ocular motility disorders.
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Transient anisocoria lasting a day in a patient with benign episodic pupil mydriasis.
Pathophysiology
Benign episodic pupillary mydriasis
has a characteristic triad of findings: (1)
episodic, transient unilateral pupil dilation, usually in young healthy females;
(2) peculiar sensations in and about the
affected eye with progression to headache or possible associated migraine;
and (3) defective accommodation without evidence of lid or ocular motility
dysfunction. The underlying etiology of
benign episodic pupillary mydriasis is
unknown. While the anisocoria is greater in bright room illumination pointing
to a painful dysfunction within the parasympathetic pupillary pathway, there is
no associated ocular motility disorder
suggestive of compressive aneurysmal
cranial nerve III palsy.
It has been postulated that brief
spasms of segments of the pupil radial
muscle leads to this intermittent dilation. However, in those cases, the pupil
will often be tadpole-shaped. In true
cases of benign episodic pupil mydriasis, the pupil is round. Thus, this is
not a plausible explanation. There
have been instances where an irritative
lesion in Pancoast’s tumor compressed
sympathetic fibers near the superior
cervical ganglion, resulting in a reverse
Horner’s syndrome that resolved with
the removal of the tumor. However,
this phenomenon did not have the
same characteristics as benign episodic
pupillary mydriasis.
It is commonly believed that benign
episodic pupillary mydriasis occurs due
to an atypical migraine phenomenon. It
is not uncommon for ophthalmoplegic
migraines to present with anisocoria.
However, the anisocoria in migraine
tends to last longer, particularly with
repeated episodes. Also, in these types
of migraines, there is ophthalmoplegia.
Benign episodic pupillary mydriasis is
unique as an entity because it does not
have ophthalmoplegia as a component
of its presentation.
A report examining the relationship between migraine and mydriasis
strongly suggested a pathogenic link
between the pupil dysfunction and
migraine, rather than a simultaneous coexistence of two independent
disorders.11 Other theories attempting
to explain the presentation included
a latent Adie’s pupil that could have
been triggered by migraine; a ciliary
ganglionic dysfunction produced by the
migraine process and an episodic ciliary
ganglionitis with migraine features.11
Ciliary ganglioplegic migraine was
proposed as a term identifying a possible anatomic source of the migrainerelated pupil dysfunction.11
Medical examination of patients
with benign episodic pupillary mydriasis, including serology, MRI, cerebral
angiography and lumbar puncture with
CSF analysis has failed to disclose any
associated abnormalities.
Management
The most important aspect in management of benign episodic pupillary
mydriasis is correct diagnosis. To this
end, it must be differentiated from
JUNE 15, 2012
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Clinical Pearls
• With a sudden dilation of the
pupil, most practitioners worry that
there is a life threatening aneurysm.
While there have been cases reported
where an aneurysm compressed CN
III without initially involving the
pupil, there has never been a reported
instance where an aneurysm compressed CN III involving only the pupil
and not ocular motility. If the pupil is
dilated and there is no ocular motility
deficit, you can rest assured that there
isn’t an aneurysm.
• Sudden unilateral pupil dilation in
a young healthy female with concurrent
headache and near vision disturbance
occurs more commonly than realized
and should be considered to be benign
episodic pupillary mydriasis until proven other wise.
• Pupillary mydriasis, pupil dysfunction and accommodation anomalies
can occur pharmacologically from
exposure to parasympatholytic agents
such as scopolamine from motion sickness preparations and the handling of
certain plants, such as jimson weed.
In these cases, the pupil will be totally
unreactive to light and near stimuli.
The use of pilocarpine 1% solution will
also fail to produce miosis.
• Pupillary mydriasis and dysfunction can also occur due to overuse
of sympathomimetic agents, such as
those found in over the counter topical allergy and whitening/vasoconstriction medications. In these cases,
the pupil will be responsive to light
and near stimuli.
1. Sowka J, Guastella P. Benign episodic pupillary
mydriasis. Southern J Optom. 1994;12(3): 26-7.
2. Chadha V, Tey A, Kearns P. Benign episodic unilateral mydriasis. Eye (2007) 21,118–9.
3. Balaguer-Santamaria JA, Escofet-Soteras C,
Chumbe-Soto G, Escribano-Subias J. Episodic benign
unilateral mydriasis. Clinical case in a girl. Rev Neurol.
2000;31(8):743-5.
4. Jacobson DM. Benign episodic unilateral
mydriasis. Clinical characteristics. Ophthalmology.
1995;102(11):1623-7.
5. Manai R, Timsit S, Rancurel G. Unilateral benign episodic mydriasis. Rev Neurol (Paris). 1995;151(5):344-6.
6. Hallett M, Cogan DG. Episodic unilateral mydriasis in otherwise normal patients. Arch Ophthalmol.
1970;84(2):130-6.
7. Evans RW, Jacobson DM. Transient anisocoria in a
migraineur. Headache. 2003;43(4):416-8.
8. Woods D, O’Connor PS, Fleming R. Episodic unilateral mydriasis and migraine. Am J Ophthalmol. 1984
15;98(2):229-34.
9. Takeda K, Sakuta M, Takano T. Recurrent episodic unilateral mydriasis with pleocytosis in the
cerebrospinal fluid--a case report. Rinsho Shinkeigaku.
1989;29(9):1186-8.
10. Zak TA. Benign episodic bilateral juvenile internal
ophthalmoplegia. J Pediatr Ophthalmol Strabismus.
1983;20(1):8-10.
11. Barriga F, López de Silanes C, Gili P, et al. Ciliary
ganglioplegic migraine: Migraine-related prolonged
mydriasis. Cephalalgia. 2010 Sep 16. [Epub ahead of
print].
DUANE’S RETRACTION
SYNDROME
Signs and Symptoms
Duane’s retraction syndrome (DRS)
is a congenital, non-progressive disorder of ocular motility that is characterized by limited abduction, limited
adduction, or both. The hallmark clinical signs that allow for differentiation
from other strabismus syndromes are
the classic retraction of the globe and
NEURO-OPHTHALMIC DISEASE
tonic pupil syndrome, pharmacologically dilated pupil, and pupil involvement from compression-related
aneurysmal cranial nerve III palsy.
In aneurysm-related CN III palsy,
there will be ophthalmoplegia and
ptosis, whereas motility and eyelid
position is normal in benign episodic
pupillary mydriasis. In tonic pupil
syndrome, there will be no return to
normal size; thus it is not episodic. In
a pupil pharmacologically dilated by
a parasympatholytic agent, there will
be no direct or accommodative pupillary responses. Further, there will be
no response to the administration of
topical pilocarpine. Once benign episodic pupillary mydriasis is diagnosed,
no further testing or management is
necessary beyond patient education
and reassurance.
Duane’s Retraction Syndrome Type I. Right
abduction deficit (above) with retraction of the
right eye on adduction (below).
narrowing of the palpebral fissure upon
attempted adduction of the involved
eye.1-4 Most cases are unilateral, with
a greater preponderance for left-eye
involvement.1-3 Additionally, the
majority of cases are isolated, meaning
that there are no accompanying congenital anomalies. Most DRS patients
present with an orthophoric posture,
although some will demonstrate esotropia or exotropia in primary gaze, along
with a compensatory head posture that
is adopted to maintain single simultaneous binocular vision.1,2 Unusual associations can include crocodile tearing
and Marcus Gunn jaw-winking, both
forms of aberrant innervation phenomena.5,6 Undiagnosed or uncorrected
DRS can lead to amblyopic vision loss
in about 10% of patients.1
Huber described three distinct types
of DRS in 1974, and these categorizations are still widely used today.7
• Type I represents the most common variant, occurring in 75% to 80%
of cases.1 Its characteristic presentation includes “marked limitation or
complete absence of abduction, normal or
only slightly defective adduction [along
with] narrowing of the palpebral fissure
and retraction of the affected eyeball on
adduction [and] widening of the palpebral
fissure on attempted abduction.”7 Women
are affected more commonly than men
in Type I, with a ratio of 60:40.3
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• Type II is seen less commonly, in
approximately 5% to 10% of cases.1 It
may be described clinically as a “… limitation or complete defect of adduction with
exotropia of the affected eye. Abduction
appears to be normal or only slightly limited. There is further distinct narrowing of
the palpebral fissure and retraction of the
globe on attempted adduction.”7 Type II
DRS shows no real gender differences
in clinical practice.1
• Type III accounts for ~10% to
20% of all DRS cases. It is defined
as a “… limitation or absence of both
abduction AND adduction of the affected
eye. There is further characteristic retraction of the globe and narrowing of the
palpebral fissure on attempted adduction.”1 Clinicians are more likely to
observe an upshoot or downshoot
of the affected globe on attempted
adduction in Type III as opposed to
the other two forms of DRS.1
Up to 30% of DRS cases demonstrate systemic associations, including
such conditions as: limb abnormalities,
cardiac abnormalities, neurosensory
deafness, Goldenhar syndrome (oculovertebralauricular dysplasia), KlippelFeil syndrome (shortness of neck
secondary to cervical vertebrae absence
or fusion), Wildervanck syndrome
(Klippel-Feil + labyrinthine deafness)
and Marfan syndrome.8
Pathophysiology
DRS may be described as a congenital cranial dysinnervation disorder. The
condition is characterized by abnormal
development of the cells in the abducens
nucleolus (CN VI), resulting in restricted or absent abduction and erroneous
innervation of the lateral rectus muscle
by branches emanating from oculomotor nuclei (CN III). Anatomic and
histologic pathology show that, between
four and eight weeks of gestation, there
is maldevelopment or injury to developing structures of the CN VI nucleus and
nerve(s). Branches from the third nerve
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are then redirected to the lateral rectus,
causing a wide spectrum of anomalous
innervations.4 The fact that DRS seems
to demonstrate a familial inheritance
pattern in at least 10% of cases suggests
that the condition is not simply due
to a sporadic mutation or to trauma.9
Although numerous chromosomal
abnormalities may be associated with
DRS, two important loci have been
mapped; these are 8q13 (DRS Type I)
and 2q31 (DRS Type II).10 A number
of cases have also been reported in association with chromosomal duplications
and rearrangements.10-13 While autopsy
studies are limited, individuals with
absent CN VI nerves and/or nuclei have
been reported.14,15 The exact pathophysiology remains elusive, but mechanically, DRS is explained by the poorly
understood development of abnormal
communication with the lateral rectus
via the inferior division of cranial nerve
III. This “miswiring” produces the classic, dual, electromyographic firing of the
recti upon attempted adduction, resulting in globe retraction and palpebral
fissure narrowing.
Management
The initial step in managing patients
with DRS is differentiating this essentially benign condition from other disorders of ocular motility. Some of the
motility disorders that must be ruled
out include: acquired sixth nerve palsy,
internuclear ophthalmoplegia, congenital esotropia with significant medial
rectus contractures, Graves disease with
extraocular muscle involvement and
medial orbital wall fracture with incarceration of the medial rectus.3 Testing
of suspected DRS patients should
include a thorough family history,
cover test in primary gaze and determination of habitual head position,
careful evaluation of motility patterns
including versions (binocular), ductions
(monocular) and possibly even forced
duction testing. If systemic complica-
tions are suspected, a comprehensive
physical examination and neuroimaging may also be warranted.3
In most cases, therapeutic intervention is unnecessary for patients with
DRS, as they typically develop effective
sensory adaptations to overcome their
limitations of motility. The major indications for surgical management are
an abnormal head position of greater
than 15° and/or a significant deviation
in primary position of gaze, where the
risk of amblyopia appears certain.16
Options typically include horizontal
rectus muscle recession or vertical rectus muscle transposition. “Y-splitting”
of the lateral rectus muscle with recession and resuturing of the sections
above and below the original axis may
be employed for patients with significant up/downshoot, or severe globe
retraction.17 Amblyopia in DRS is
treated conventionally by prescribing
full correction spectacles, direct patching therapy and intensive, well-monitored vision therapy.
Clinical Pearls
• DRS has a prevalence of 0.1% in
the general population and accounts for
1% to 5% of all strabismus cases.3,4,8,16
• Since systemic abnormalities are
present in a significant number of cases,
a complete health examination with
blood work, hearing and EKG is recommend for all new diagnoses of DRS.
• The differential diagnosis for
DRS should include epicanthal folds,
congenital esotropia with and without
an accommodative component, convergence excess, accommodative excess,
excessive hyperopia with resultant
esotropia, Brown’s syndrome (limited
elevation and adduction secondary to
a restriction of the superior oblique via
inflammation or scarring in the area of
the trochlear tendon), double elevator
palsy (congenital limitation of up gaze),
Mobius syndrome (congenital unilateral or bilateral limitation of horizontal
JUNE 15, 2012
6/1/12 3:33 PM
1. Andrews CV, Hunter DG, Engle EC. Duane
Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens
K, eds. GeneReviews [Internet]. Seattle (WA): University
of Washington, Seattle; 1993-. 2007 [updated 2010
Feb 18].
2. Park WH, Son DH, Yoon SW, et al. The clinical
features of Korean patients with Duane’s retraction syndrome. Korean J Ophthalmol. 2005;19(2):132-5.
3. Bhola R, Graff JM. Duane Retraction Syndrome: 31
year-old Male with Globe Retraction. June 1, 2006.
Available at: www.EyeRounds.org/cases/56-DuanesRetraction-Syndrome.htm. Accessed February 10,
2012.
4. Yüksel D, Optican LM, Lefèvre P. Properties of saccades in Duane retraction syndrome. Invest Ophthalmol
Vis Sci. 2005;46(9):3144-51.
5. Mugundhan K, Thiruvarutchelvan K, Sivakumar S.
Congenital crocodile tears with Duane’s syndrome—
congenital cranial dysinnervation syndrome. J Assoc
Physicians India. 2011;59:316.
6. Oltmanns M, Khuddus N. Duane retraction syndrome
type I, marcus gunn jaw-winking and crocodile tears
in the same eye. J Pediatr Ophthalmol Strabismus.
2010;47 Online:e1-3.
7. Huber A. Electrophysiology of the retraction syndromes. Br J Ophthalmol. 1974;58(3):293-300.
8. Kothari M, Manurung F, Mithiya B. Simultaneous
occurrence of Duane Retraction Syndrome with
Marfan Syndrome. Case Reports in Ophthalmological
Medicine. 2011, Article ID 784259, 3 pages.
doi:10.1155/2011/784259.
9. Kirkham TH. Inheritance of Duane’s syndrome. Br J
Ophthalmol. 1970;54(5):323-9.
10. Smith SB, Traboulsi EI. Duane syndrome in the
setting of chromosomal duplications. Am J Ophthalmol.
2010;150(6):932-8.
11. Weis A, Bialer MG, Kodsi S. Duane syndrome
in association with 48,XXYY karyotype. J AAPOS.
2011;15(3):295-6.
12. Gómez-Lado C, Eirís J, Martínez-Yriarte JM,
et al. Duane’s syndrome and 22 marker chromosome: a possible cat-eye syndrome. Acta Paediatr.
2006;95(11):1510-1.
13. Versteegh FG, von Lindern JS, Kemper J, et al.
Duane retraction syndrome, a new feature in 22q11
deletion syndrome? Clin Dysmorphol. 2000;9(2):135-7.
14. Hotchkiss MG, Miller NR, Clark AW, Green WR.
Bilateral Duane’s retraction syndrome: a clinical-pathologic case report. Arch Ophthalmol. 1980;98(5):870-4.
15. Miller NR, Kiel SM, Green WR, Clark AW. Unilateral
Duane’s retraction syndrome (type 1). Arch Ophthalmol.
1982;100(9):1468-72.
16. Barbe ME, Scott WE, Kutschke PJ. A simplified
approach to the treatment of Duane’s syndrome. Br J
Ophthalmol. 2004;88(1):131-8.
17. Rao VB, Helveston EM, Sahare P. Treatment of
upshoot and downshoot in Duane syndrome by recession and Y-splitting of the lateral rectus muscle. J
AAPOS. 2003;7(6):389-95.
HORNER’S SYNDROME
Signs and Symptoms
Horner’s syndrome is characterized
by an interruption of the oculosympathetic nerve supply somewhere between
its origin (in the hypothalamus) and
the eye.1-9 The classic clinical findings
associated with Horner’s syndrome are
ptosis, pupillary miosis, facial anhidrosis, apparent enophthalmos, increased
amplitude of accommodation, heterochromia of the irides (if congenital or
occurring before the age of two years),
paradoxical contralateral eyelid retraction, transient decrease in intraocular
pressure and changes in tear viscosity.1-9 Horner’s syndrome has no predilection for age, race, gender or geographic location. Horner’s syndromes
of congenital origin present around the
age of two years with heterochromia
and absence of a horizontal eyelid fold
or crease in the ptotic eye.1-5,9 Iris
pigmentation (which is under sympathetic control during development) is
completed by the age of two, making
heterochromia an uncommon finding
in Horner’s syndromes acquired later
in life.1-3 Old photographs can aide the
clinician in distinguishing congenital
Horner’s by documenting heterochromia present at birth.1-5
Pathophysiology
Sympathetic innervation to the eye
consists of a three-neuron arc.1-10 The
first neuron originates in the dorsolateral
hypothalamus. It descends through the
reticular formation of the brainstem
and travels to the ciliospinal center of
Budge, between the levels of the eighth
cervical and fourth thoracic vertebrae
(C8-T4) of the spinal cord. There, it
synapses with second order neurons
whose preganglionic cell bodies give rise
to axons that exit the white rami communicantes of the spinal cord via the
anterior horn. These axons pass over the
apex of the lung and enter the sympathetic chain in the neck, synapsing in
the superior cervical ganglion.1-9 Here,
cell bodies of third order neurons give
rise to postganglionic axons that course
to the eye with the internal carotid
artery via the cavernous sinus.1-10 Fibers
from these axons form the long and
short posterior ciliary nerves of the eye.
These sympathetic nerve fibers course
anteriorly through the uveal tract and
join the fibers of long posterior ciliary
nerves, which course with branches of
the fifth cranial nerve, to innervate the
dilator of the iris. Postganglionic sympathetic fibers also innervate the muscle
of Mueller, responsible for the initiation
of eyelid retraction during eyelid opening. Postganglionic sympathetic fibers
responsible for facial sweating follow
the external carotid artery to the sweat
glands of the face.1-10 Interruption at
any location along this pathway (preganglionic or postganglionic) will induce
an ipsilateral Horner’s syndrome.
Management
The diagnosis of a suspected
Horner’s syndrome can be accomplished with pharmacological testing.5-9
In this dysfunction, there is a lack
of the sympathetic neurotransmitter
norepinephrine. The iris dilator does
not receive sympathetic stimulation in
Horner’s syndrome, thus accounting
for the miosis that increases in dim
light conditions and the dilation lag
(relative to the normal contralateral
pupil) when the lights go down.
Topically applied 10% cocaine
works as an indirect-acting sympathomimetic agent, producing pupillary
dilation in the normally innervated
pupil by inhibiting the reuptake of
norepinephrine at the nerve ending.4-9
A Horner’s pupil will dilate poorly
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NEURO-OPHTHALMIC DISEASE
eye movements + facial nerve palsy),
congenital fibrosis syndrome (congenital ptosis and external ophthalmoplegia
with limited horizontal gaze), CN VI
palsy, Grave’s disease and orbital pseudotumor.
• In general, children with DRS
benefit the most from surgical intervention. Adults are usually not candidates for surgery unless the condition is
cosmetically unacceptable.
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Left ptosis and miosis in a patient with Horner’s
syndrome.
Reversal of ptosis and miosis 30 minutes after
instillation of apraclonidine.
compared to the normal eye because
of the absence of norepinephrine at
the nerve ending.4-9 The test should
be evaluated thirty minutes after the
instillation of the drops to ensure
accuracy. The cocaine test is used to
confirm or deny the presence of a
Horner’s syndrome. A positive cocaine
test does not localize the lesion.1-9
However, topical liquid cocaine is
a controlled substance and not readily
available, and Paredrine (hydroxyamphetamine, Akorn), historically used
to localize the lesion, is no longer
available. To that end, it appears
that Iopidine (apraclonidine 1% and
0.5%, Alcon) can be used effectively
to diagnose Horner’s syndrome.11-16
Apraclonidine is an alpha-2 adrenergic agonist that seems to also stimulate alpha-1 receptors to a negligible
degree in the normal state. Pupil dilation in suspected Horner’s syndrome
is considered diagnostic. The theory
is that the Horner’s syndrome pupil
undergoes denervation hypersensitivity
with upregulation of both the number
and sensitivity of available receptors.
When a very weak alpha-1 adrenergic
agonist is applied, the hypersensitive
pupil dilates while the normal pupil
has no effect. In most cases, there will
actually be a reversal of the anisocoria, which is easier to appreciate than
the asymmetric dilation induced by
cocaine. It appears that the most readily available agent, apraclonidine 0.5%,
is at least as sensitive and specific in
the diagnosis of Horner’s syndrome as
is cocaine.15,16
There exist concerns with apraclonidine testing. The main concern
is the possibility of false-negative
responses.12,14 This can occur if reversal
of anisocoria is demanded to make the
diagnosis, as reversal may not occur
in all patients—though there may
be sympathetic effects such as ptosis
improvement or some degree of mydriasis in the affected eye.14 Additionally,
false-negative results may occur if
apraclonidine is used too early after the
onset of Horner’s syndrome because
it takes time, typically several weeks,
before denervation hypersensitivity
develops. However, there are reports of
positive apraclonidine tests only several
hours after the onset of symptoms and
Horner’s syndrome.13,17
The common etiologies of acquired
Horner’s syndrome include, but are
not limited to: trauma, aortic dissection, carotid dissection, tuberculosis,
and Pancoast syndrome.1-9 Aortic dissection is a tear in the intimal region
of the ascending aorta near the aortic
valve.1-9 It often occurs along the right
lateral wall of the ascending aorta
where the hydraulic stress is the greatest.1-9 Compression of adjacent tissues
(e.g., superior cervical ganglia, superior vena cava, bronchus, esophagus)
by the expanding dissection, can result
in Horner’s syndrome, superior vena
cava syndrome, vocal cord paralysis,
hoarseness, dysapnea, and dysphagia.
Patients with long-standing systemic
hypertension, Marfan’s syndrome
and Ehler’s Danlos syndrome are at
increased risk.1-9
In that the oculosympathetic plexus
travels with the abducens nerve for a
short distance within the cavernous
sinus, the combination of a Horner’s
syndrome and cranial nerve VI paralysis indicates a parasellar lesion within
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the cavernous sinus. Typically the
lesion is an aneurysm of the parasellar
internal carotid artery.18,19
If the patient reports recent ipsilateral neck trauma, neck and face
pain, ipsilateral transient monocular
visual loss, or contralateral transient
weakness or numbness, acute cervical
carotid dissection must be immediately suspected. In this case, there
is a substantial risk of hemispheric
(middle cerebral artery distribution)
stroke within the first two weeks of
onset. Cervical carotid dissection is
a relatively common cause of acute
onset Horner’s syndrome.20-22
The patient should be questioned
for a history of previous accidental
or surgical trauma to the neck, upper
spine or chest. Trauma, including
carotid endarterectomy and epidural anesthesia, is a common cause of
Horner’s syndrome.23,24 The patient
should also be questioned regarding
any history of migraine headache.
As the oculosympathetic plexus
courses over the lung apex, various pulmonary diseases can cause a
Horner’s syndrome. Pancoast syndrome is a malignancy of the superior
pulmonary sulcus carcinoma, with
subsequent destruction of the thoracic
inlet and involvement of the brachial
and oculosympathetic plexuses.25
Most cases involve non-small cell lung
carcinoma. The oculosympathetic
plexus is prone to compression by a
malignant space-occupying lesion as
it courses over the superior aspect of
the lung. This would cause a second
order lesion. The Horner’s syndrome
is accompanied by shoulder pain radiating to the axilla and scapula. There
is also atrophy of the hand and arm
with resultant muscle weakness. Bony
structures of the chest are often invaded by the malignancy, especially the
thoracic vertebrae and ribs. Clinical
characteristics of Pancoast syndrome
include shoulder pain, loss of limb
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6/5/12 9:42 AM
the upper chest, neck and brain must
be done.28 It is recommended to order
magnetic resonance imaging (MRI) of
the chest to include the lung apex and
brachial plexus, magnetic resonance
angiography (MRA) or CT angiography of the neck and cervical spine, and
MRI of the middle cranial fossa. Even
with such extensive testing, a cause is
rarely uncovered with such untargeted
evaluations.28
In general, the treatment for
Horner’s syndrome depends upon
the cause. In many cases, there
is no treatment that improves or
reverses the condition. Treatment
in acquired cases is directed toward
eradicating the cause. Recognizing
the signs and symptoms is tantamount to early diagnosis, as is making expedient referrals to appropriate
medical specialists.
Clinical Pearls
• Horner’s syndrome can be considered not just a diagnosis, but also
a finding that should be investigated
for a cause. Diagnosing Horner’s syndrome is not the challenge. The challenge is finding the cause.
• In cases where the onset is acute
and the exam gives no clues as to the
cause, the patient must be imaged from
the chest to the brain.
1. Wilkins RH, Brody IA, Durham NC. Horner’s syndrome. Arch Neurol 1968;19:540-2.
2. Horner F. Uber eine form von ptosis. Klin Monatsbl
Augenh 1869;7:193.
3. Tantum LA. Pupil anomalies. In: Onofrey BE (ed).
Clinical optometric pharmacology and therapeutics.
Philadelphia; JB Lippincott,1991;13:1-13.
4. Burde RM, Savino,RJ, Trobe JD. Anisocoria and
abnormal pupillary light reaction. In: Burde, RM, Savino,
PJ, Trobe, JD (eds). Clinical Decisions in NeuroOphthalmology, 2nd ed. St. Louis.; Mosby, 1992:32146.
5. Myles WM, Maxner CE. Localizing value of concurrent
sixth nerve paresis and postganglionic Horner’s syndrome. Can J Ophthalmol 1994;29(1):39-42.
6. Maloney WF, Younge BR, Moyer NJ. Evaluation of the
causes and accuracy of pharmacologic localization in
Horner’s syndrome. Am J Ophthalmol 1980;90(3):394402.
7. Bates AT, Chamberlain S, Champion M, et al.
Pholedrine: a substitute for hydroxyamphetamine as a
diagnostic eyedrop test in Horner’s syndrome. J Neurol
Neurosurg Psychiatry 1995;58(2):215-7.
8. Thompson HS, Pilley SFJ. Unequal pupils: a flow chart
for sorting out the anisocorias. Surv Ophthalmol 1976;
21(1):45-8.
9. Cullom RD, Chang B. Neuro-ophthalmology: Horner’s
Syndrome. In: Cullom RD, Chang B (eds). The Wills Eye
Manual, 2nd ed. Philadelphia; JB Lippincott, 1993:241-6.
10. Alstadhaug KB. Acquired Horner’s syndrome.
Tidsskr Nor Laegeforen. 2011;131(9-10):950-4.
11. Mughal M, Longmuir R. Current pharmacologic
testing for Horner syndrome. Curr Neurol Neurosci Rep.
2009;9(5):384-9.
12. Dewan MA, Harrison AR, Lee MS. False-negative
apraclonidine testing in acute Horner syndrome. Can J
Ophthalmol. 2009;44(1):109-10.
13. Lebas M, Seror J, Debroucker T. Positive apraclonidine test 36 hours after acute onset of horner
syndrome in dorsolateral pontomedullary stroke. J
Neuroophthalmol. 2010;30(1):12-7.
14. Kawasaki A, Borruat FX. False negative apraclonidine
test in two patients with Horner syndrome. Klin Monbl
Augenheilkd. 2008;225(5):520-2.
15. Koc F, Kavuncu S, Kansu T, et al. The sensitivity
and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol.
2005;89(11):1442-4.
16. Freedman KA, Brown SM. Topical apraclonidine
in the diagnosis of suspected Horner syndrome. J
Neuroophthalmol. 2005;25(2):83-5.
17. Cooper-Knock J, Pepper I, Hodgson T, Sharrack B.
Early diagnosis of Horner syndrome using topical apraclonidine. J Neuroophthalmol. 2011;31(3):214-6.
18. Rose J, Jacob P, Jacob T. Horner syndrome and
VI nerve paresis as a diagnostic clue to a hidden lesion.
Natl Med J India. 2010;23(6):344-5.
19. Mangat SS, Nayak H, Chandna A. Horner’s syndrome and sixth nerve paresis secondary to a petrous
internal carotid artery aneurysm. Semin Ophthalmol.
2011;26(1):23-4.
20. Rohrweck S, España-Gregori E, Gené-Sampedro
A, et al. Horner syndrome as a manifestation of
carotid artery dissection. Arch Soc Esp Oftalmol.
2011;86(11):377-9.
21. Willett GM, Wachholtz NA. A patient with internal
carotid artery dissection. Phys Ther. 2011;91(8):1266-74.
22. Flaherty PM, Flynn JM. Horner syndrome due to
carotid dissection. J Emerg Med. 2011;41(1):43-6.
23. Goel S, Burkat CN. Unusual case of persistent
Horner’s syndrome following epidural anaesthesia and
caesarean section. Indian J Ophthalmol. 2011;59(5):38991.
24. Barbara R, Tome R, Barua A, et al. Transient Horner
syndrome following epidural anesthesia for labor: case
report and review of the literature. Obstet Gynecol Surv.
2011;66(2):114-9.
25. Sartori F, Rea F, Calabro F, et al. Carcinoma of the
superior pulmonary sulcus. J Thorac Cardiovasc Surg.
1992;104:679-83.
26. Bansal M, Martin SR, Rudnicki SA, et al. A rapidly
progressing Pancoast syndrome due to pulmonary
mucormycosis: a case report. J Med Case Reports.
2011;5:388.
27. Ikeuchi T, Tokutake T, Sakamaki Y, et al.
Progression of cluster headache to Raeder’s syndrome
with marked response to corticosteroid therapy: a case
report. Rinsho Shinkeigaku 2005;45(4):321-3.
28. Almog Y, Gepstein R, Kesler A. Diagnostic
value of imaging in horner syndrome in adults. J
Neuroophthalmol. 2010;30(1):7-11.
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NEURO-OPHTHALMIC DISEASE
function, atrophy of the muscles of
the hand, Horner’s syndrome and
dullness of feeling in the region of the
upper chest.25
A true Pancoast tumor usually
extends through the visceral pleura into
the parietal pleura and chest wall. The
tumor is considered to be epithelial in
its histopathology, but its exact origin
remains uncertain. Despite its small
size and general lack of metastasis,
Pancoast tumor has a rapid and almost
universal mortality rate. Approximately
80% to 90% of all lung cancers are
linked or associated with smoking.25
Occasionally a Pancoast syndrome
may be from a infectious etiology, such
mucormycosis or tuberculosis. If the
infectious agent or tuberculosis tubercle
occupies a position at the lung apex,
it may compress preganglionic sympathetic axons producing a Horner’s
syndrome.26
The unique presentation of unilateral headache, partial Horner’s
syndrome and V1 sensory disturbance,
in the presence of negative neuroimaging studies may identify the rare entity
know as Raeder’s syndrome.27 This
vasculopathic postganglionic malady
produces a painful Horner’s syndrome
that may be remedied, in most cases,
with pharmacologic agents. There has
been a report in the literature linking
this unusual syndrome to the cluster
migraine headache.27
Based upon the history and physical
findings, patients with Horner’s syndrome should undergo a targeted evaluation if the cause is not already clear.
In many cases such as recent trauma,
the cause may be known or, in the case
of associated acute neck and face pain,
suspected with a degree of certainty. In
these cases, medical evaluation and neuroimaging may be unnecessary or may
be targeted to the suspected etiology. If,
in the course of examination, no diagnostic clues are identified, a non-targeted evaluation consisting of imaging of
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