Lesion	HSV Dendrite	HZV Pseudodendrite
Appearance	Delicate, fine, lacy ulcer	Coarse, ropy, elevated, ’painted-on’ lesion
		Smaller, less branching than HSV dendrite
	Terminal bulbs	Blunt ends (no terminal bulbs)
	Epithelial cells slough	Epithelial cells are swollen and heaped-up
Staining	Base with fluorescein	Poor with fluorescein and rose bengal
	Edges with rose bengal
Treatment	Do not use steroids	Good response to steroids

Note: Active viral replication in epithelial lesions occurs in both HSV and HZV

Other causes of pseudodendrite: Acanthamoeba, tyrosinemia II, epithelial healing ridge

Chickenpox

Findings

papillary conjunctivitis, ‘pock’ lesions on bulbar conjunctiva and at limbus, keratitis (dendritic, disciform, interstitial)

Fungi

Types

Molds (filamentous): form hyphae

SEPTATE: most common cause of fungal keratitis; most common in southern / southwestern United States – Fusarium (F. solani is most virulent), Aspergillus, Cuvularia, Paecilomyces, Penicillium, Phialophora

NONSEPTATE: Mucor (rare cause of keratitis)

Yeast: Candida (most common cause of mycotic ocular infections in northern United States), Cryptococcus (associated with endogenous endophthalmitis; rarely keratitis)

Dimorphic fungi: grow as yeast or mold – Histoplasma, Blastomyces, Coccidioides

Risk factors

Molds: corneal injury especially from tree branch or vegetable material, soft contact lens wear

Yeast: therapeutic soft contact lens wear, topical steroid use, nonhealing epithelial defect, decreased host resistance

Findings

satellite infiltrates, feathery edges, endothelial plaque; can penetrate Descemet’s membrane

Treatment

topical antifungal (natamycin 5% [filamentous], clotrimazole [Aspergillus], amphotericin B 0.15% [yeast], flucytosine 1%, ketoconazole 2%, miconazole 1%, itraconazole 1%, fluconazole 0.5%); cycloplegic

Corneal epithelium is significant barrier to natamycin penetration

Acanthamoeba

22 species; exists as trophozoite or cyst

90% initially misdiagnosed as HSV

Risk factors

cleaning soft contact lenses with homemade saline solution; swimming or hot tubbing while wearing contact lenses

Prevention

heat disinfectant (75°C)

Findings

epithelial cysts (can look like EKC with subepithelial infiltrates and punctate keratopathy), perineural infiltrate (enlarged corneal nerves, decreased corneal sensation, pain [perineuritis]), ring-shaped infiltrate, corneal edema, pseudodendrite, iritis, hypopyon (30–40%), scleritis; may perforate

Diagnosis

calcofluor white, Giemsa stain, culture (non-nutrient agar with E. coli overlay; can grow on blood or chocolate agar but not as well), confocal microscopy

Pathology

oval amoebic double-walled cysts in stroma

Treatment

débridement if infection limited to epithelium (may be curative), topical agents

Antibacterial: neomycin, paromomycin (Humatin) 1% 6-8×/day

Antifungal: miconazole 1%, clotrimazole 1%; ketoconazole or itraconazole (oral)

Antiparasitic: propamidine isethionate (Brolene) 0.1% 6×/day, hexamidine (Desomedine) 0.1%, pentamidine (Biocide), polyhexamethylene biguanide (PHMB, Baquacil; swimming pool cleaner) 0.02%, chlorhexidine 0.02%

Steroid: controversial

30% recurrence after penetrating keratoplasty

Onchocerciasis

(See Ch. 8, Uveitis)

Leprosy

(See Ch. 8, Uveitis)

Epstein-Barr Virus (EBV)

Findings

multifocal stromal keratitis; may rarely have episcleritis, follicular conjunctivitis, uveitis, optic neuritis

Diagnosis

Antibodies: viral capsid antigen IgM and IgG and early antigen-diffuse (EA-D) peak at 6–12 weeks; viral capsid antigen (VCA)-IgM and Epstein-Barr nuclear antigen (EBNA) are detectable for life; heterophile antibodies (IgM that reacts to horse and sheep blood cells) peak at 2–3 weeks and last 1 year (Monospot test)

Lymphocytosis: occurs in 70%; peaks at 2–3 weeks

Liver enzymes: elevated

Ectasias

Keratoconus

90% bilateral; onset typically around puberty

Associations

Systemic conditions: atopy (eye rubbing), Down’s syndrome, connective tissue disease (Ehlers-Danlos syndrome, Marfan’s syndrome, osteogenesis imperfecta)

Ocular conditions: aniridia, retinitis pigmentosa, VKC, Leber’s congenital amaurosis, ectopia lentis, floppy eyelid syndrome, CHED, posterior pPolymorphous dystrophy (PPMD)

Findings

inferior corneal protrusion, stromal thinning at cone apex (apical thinning), apical scarring, Fleischer ring (epithelial iron deposition at base of cone), Vogt’s striae (fine deep striae anterior to Descemet’s membrane; disappear with external pressure), prominent corneal nerves, scissors reflex on retinoscopy, Munson’s sign (angulation of lower lid on downgaze due to corneal protrusion), Rizzutti’s sign (conical reflection of light from temporal light source on nasal iris); may develop hydrops

Hydrops: acute corneal edema and clouding due to break in Descemet’s membrane; painful or painless; decreased IOP; heals over 6–10 weeks; scarring can occur occasionally with stromal neovascularization

Pathology

breaks in Bowman’s membrane, stromal folds, superficial scarring, stromal thinning; Descemet’s is normal unless hydrops has occurred (breaks with curled edges covered by adjacent endothelial cells and new Descemet’s)

DDx

contact lens-induced corneal warpage, pellucid marginal degeneration, keratoglobus

Diagnosis

corneal topography (irregular astigmatism, central or inferior steepening), keratometry (steep readings, irregular mires)

Treatment

contact lenses (rigid, piggyback) for visual improvement; rigid contact lenses do not stop progression of disease. Corneal collagen crosslinking, Intacs (to stop progression); penetrating keratoplasty for advanced cases; supportive for hydrops (topical steroids, cycloplegic, bandage contact lens)

Posterior Keratoconus

(See Ch. 5, Pediatrics / Strabismus)

Keratoglobus

Rare, sporadic, globular corneal deformity

Associated with connective tissue disorders, Leber’s congenital amaurosis

Findings

bilateral corneal thinning, maximal in midperiphery at base of protrusion

Treatment

CL (rigid), penetrating keratoplasty

Dystrophies

Inherited genetic disorders (usually defective enzyme or structural protein)

AD except macular, type 3 lattice, gelatinous, and nystagmus-associated form of CHED, which are AR

Genetics

many dystrophies have a mutation of the BIGH3 (TGFBI) gene on chromosome 5. These dystrophies tend to be AD and include granular, Avellino’s, lattice types 1 and 3, Reis-Bucklers’, and Thiel-Behnke’s

Onset by age 20 years, except anterior basement membrane dystrophy (ages 30–40), pre-Descemet’s (ages 30–40), and Fuchs’ (ages 40–50)

Not associated with systemic diseases, except central crystalline dystrophy (associated with hypercholesterolemia with or without hyperlipidemia), and type 2 lattice (Meretoja’s syndrome associated with systemic amyloidosis)

Affect central cornea, except Meesmann’s, macular, fleck, CHED, and CHSD, which extend to limbus

Anterior Basement Membrane (Cogan’s Microcystic; Map-Dot-Fingerprint) (AD)

Most common anterior corneal dystrophy

Usually bilateral, can be asymmetric; primarily affects middle-aged women

Symptoms more common in those >30 years old

Symptoms

usually asymptomatic; may have pain, redness, tearing, irritation (recurrent erosions), or decreased vision (subepithelial scarring)

Findings

irregular and often loose epithelium with characteristic appearance (map, dot, fingerprint):

Map lines: subepithelial connective tissue

Microcysts: white, putty-like dots (degenerated epithelial cells trapped in abnormal epithelium)

Fingerprints: parallel lines of basement membrane separating tongues of reduplicated epithelium

May develop recurrent erosions (10% with the dystrophy get erosions, 50% with erosions have the dystrophy) or decreased vision or monocular diplopia from subepithelial scarring (irregular astigmatism)

Pathology

epithelial reduplication with excess subepithelial and intraepithelial production of basement membrane material and collagen (due to poor epithelial adhesion to basement membrane) (Figure 7-11)

Figure 7-11 ABMD demonstrating cysts and aberrant production of basement membrane material in the epithelium.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

Treatment

none unless symptomatic. For erosions, treat with lubrication, hypertonic saline (Muro 128 5% ointment qhs × 3–12 months); if recurs, consider bandage contact lens, epithelial débridement, anterior stromal puncture / reinforcement, diamond burr (débride and polish Bowman’s membrane), laser (PTK with excimer laser, or micropuncture with Nd : YAG laser (1 mJ, aim just below epithelium)); also, consider treatment with matrix metalloproteinase-9 inhibitors (doxycycline 50 mg PO bid × 2 months and topical steroids tid × 2–3weeks); débridement for subepithelial scarring

Meesmann’s (AD)

Mapped to chromosomes 12q12 and 17

Appears early in life

Minimal symptoms, good vision

Findings

tiny epithelial vesicles, most numerous interpalpebrally, extend to limbus

Pathology

epithelial cells contain PAS-positive material (peculiar substance); thickened epithelial basement membrane (Figure 7-12)

Figure 7-12 Meesmann’s dystrophy with Periodic Acid-Schiff stain.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

No treatment

Gelatinous Drop–Like (AR)

Mapped to chromosome 1p32

Rare; occurs in 1st decade

Symptoms

decreased vision, photophobia, tearing

Findings

central, mulberry-like, subepithelial opacity

Pathology

absence of Bowman’s layer; amyloid

Reis-Bucklers’ (Corneal Dystrophy of Bowman’s Membrane Type I) (AD)

Mapped to chromosome 5q31 (BIGH3)

Appears early in life

Findings

subepithelial, irregularly shaped rings with scalloped edges and geographic gray-white reticular opacification, greatest centrally; epithelial erosions, corneal scarring

Pathology

absence of Bowman’s layer and replacement by connective tissue; irregular saw-toothed epithelium; curly filaments (electron microscopy); stain with Masson’s trichrome

Treatment

penetrating keratoplasty (recurrence is common)

Thiel-Behnke’s Dystrophy (Corneal Dystrophy of Bowman’s Membrane Type II) (AD)

Mapped to chromosomes 5q31 and 10q24

Honeycomb pattern; BIGH3 gene defect

Stromal

Mnemonic

Marilyn Monroe Always Gets Her Men in LA County

Refers to name of dystrophy, substance deposited in cornea, special stain (for the 3 classic dystrophies)

Macular, Mucopolysaccharide, Alcian blue, Granular, Hyaline, Masson’s trichrome

Lattice, Amyloid, Congo red

Lattice

Mapped to chromosome 5q31 (BIGH3)

Deposits present in 1st decade of life

Symptoms

pain, decreased vision in 2nd–3rd decade of life

Findings

branching refractile lines in anterior stroma (best seen in retroillumination), central subepithelial white dots, stromal haze with ground-glass appearance, peripheral cornea typically clear (depends on type); eventually recurrent erosions with scarring

Types

Type I (Biber-Haab-Dimmer) (AR): classic lattice dystrophy; starts centrally, spares periphery, no systemic amyloid; BIGH3 gene defect

Type II (Meretoja’s syndrome) (AR): Mapped to chromosome 9q32-34 (GSN); Finnish descent; systemic amyloidosis (facial mask; dry, lax skin; blepharochalasis, dermatochalasis; pendulous ears; cranial and peripheral nerve palsies); corneal involvement more peripheral and moves centrally

Type III (AR): Japanese descent, adult onset, thicker lattice lines, limbus to limbus, no recurrent erosions; BIGH3 gene defect

Pathology

amyloid deposits, stain with Congo red, thioflavin T, metachromatic with crystal violet, apple-green birefringence and dichroism with polarization microscopy (Figure 7-15)

Figure 7-15 Deposits in lattice dystrophy.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

Treatment

penetrating keratoplasty (recurrence more likely than in macular or granular, but less likely than in Reis-Bucklers’)

Avellino’s

Mapped to chromosome 5q31 (BIGH3)

First identified in family from Avellino, Italy

Findings

appears like granular dystrophy with interspersed lattice lines; granular deposits occur early in anterior stroma, lattice findings occur later in deeper stroma; stromal haze; may get erosions

Pathology

hyaline and amyloid deposits; stain with Masson’s trichrome and Congo red

Central Crystalline (Schnyder’s) (AD)

Mapped to chromosome 1p36

Slowly progressive, rarely reduces vision enough to require corneal transplantation

Findings

minute yellow-white crystals just beneath Bowman’s membrane in central doughnut-like pattern, diffuse stromal haze, dense arcus with age, limbal girdle of Vogt; no recurrent erosions; hyperlipidemia or hypercholesterolemia (33%); may have short forearms and genu valgum

Pathology

cholesterol and neutral fat deposits, stain with oil-red-O

Can recur in graft

Fleck (Francois-Neetans’) (AD)

Congenital, nonprogressive, asymmetric or unilateral

Usually not present before age 15

Vision usually not affected

Findings

discrete, flat, gray-white, dandruff-like speck and ring-shaped opacities, extending to periphery; decreased corneal sensation

Associated with limbal dermoid, keratoconus, central cloudy corneal dystrophy (Francois’), punctate cortical lens changes, pseudoxanthoma elasticum, atopy

Pathology

glycosaminoglycan and lipid deposits, stain with Alcian blue and colloidal iron (GAGs), Sudan black and oil-red-O (lipid)

Central Cloudy (Francois’) (AD)

Nonprogressive

Vision usually not affected

Findings

multiple, nebulous, polygonal gray areas separated by crack-like intervening clear zones (looks similar to crocodile shagreen); most dense centrally and posteriorly, fade anteriorly and peripherally

Posterior Amorphous Stromal (AD)

Early in life, minimally progressive or nonprogressive

Findings

diffuse gray-white stromal opacities concentrated in posterior stroma, mostly centrally but extends to periphery

Associated with hyperopia, central thinning, flat corneal topography, anterior iris abnormalities, fine iris processes extending to Schwalbe’s line

Congenital Hereditary Stromal (CHSD)

(See Ch. 5, Pediatrics / Strabismus)

Endothelial

Cornea Guttata

Associated with aging and with corneal endothelial dystrophy

Beaten metal appearance

Most never develop corneal edema

Pathology

thickened Descemet’s with localized excrescences of collagen; variable endothelial size and shape and reduced number on specular microscopy

Posterior Polymorphous (PPMD) (AD, Occasionally AR)

Mapped to chromosome 20p11

Minimally or nonprogressive; occurs early in life

Vision usually normal

Endothelium behaves like epithelium, forming multiple layers with occasional migration of cells into angle causing glaucoma (15%)

Findings

isolated grouped vesicles, geographically shaped discrete gray lesions, broad bands with scalloped edges; variable amounts of stromal edema, corectopia, and broad iridocorneal adhesions

Pathology

irregular blebs or vacuoles at level of Descemet’s surrounded by gray opacification, thickened Descemet’s, abnormal endothelial cells (resemble epithelial cells; contain keratin, microvilli, desmosomes)

DDx

Haab’s striae in congenital glaucoma, ICE syndrome

Treatment

penetrating keratoplasty for endothelial decompensation, can recur in graft

Congenital Hereditary Endothelial (CHED)

(See Ch. 5, Pediatrics / Strabismus)

Miscellaneous

Delle(n)

Focal thinning(s) from dehydration due to adjacent area of elevation (i.e. pingueculum, pterygium, filtering bleb)

Treatment

lubrication; punctal occlusion to raise tear film; may require removal of inciting lesion

Descemetocele

Extreme focal thinning of cornea in which only Descemet’s membrane remains

Due to corneal melt (see Corneal melt section)

High risk of perforation

Bullous Keratopathy

Corneal edema with epithelial bullae, thickened stroma, but no guttata

Due to loss or dysfunction of endothelial cells

May develop fibrovascular pannus

Etiology

aphakia, pseudophakia (rigid AC IOL), vitreocorneal touch, iridocorneal touch, sequela of severe or chronic keratitis

Pathology

blister-like elevations of corneal epithelium, damaged hemidesmosomes

DDx of corneal edema

aphakic bullous keratopathy (ABK), PBK, inflammation, infection, Fuchs’ dystrophy, PPMD, CHED, hydrops, acute angle-closure glaucoma, congenital glaucoma, graft failure, contact lens overwear, hypotony, birth trauma, ICE syndrome, anterior segment ischemia, Brown-McLean syndrome

Brown-McLean Syndrome: peripheral corneal decompensation in aphakic patients, central cornea clear

ETIOLOGY: uncertain, possibly mechanical irritation from floppy peripheral iris

Familial Dysautonomia (Riley-Day Syndrome)

(See Ch. 5, Pediatrics / Strabismus)

Exposure Keratopathy

Desiccation of corneal epithelium due to CN 7 lesion (failure to close eyelids)

Findings

epithelial defects; may develop infection, melt, perforation

Treatment

lubrication, moisture chamber goggles, lid taping at bedtime; consider tarsorrhaphy, lid weights

Contact Lens-related Problems

SPK

mechanical or chemical (solutions)

3 and 9 o’clock staining

due to poor wetting of peripheral cornea; refit lens

Abrasion

increased risk of infection in CL wearers

Treatment: topical antibiotics, never patch

Infiltrates

hypoxia, antigenic reaction to preservatives in CL solutions, infection

Treatment: stop CL wear, topical antibiotics

Edema

epithelial microcystic edema due to altered metabolism; associated with extended wear CL

Treatment: decrease wear time; switch to daily wear lenses

Giant papillary conjunctivitis (GPC)

sensitivity to CL material, deposits on CL, or mechanical irritation

Treatment: stop CL wear, topical allergy medication

Superior limbic keratoconjunctivitis (SLK)

may be due to hypersensitivity or toxic reaction to thimerosal

Treatment: resolves with discontinuation of lens wear

Neovascularization

superficial, deep, sectoral, or 360°; due to chronic hypoxia

Treatment: refit lens with increased oxygen transmission; stop lens wear if significant vascularization

Corneal warpage

irregular astigmatism related to lens material (hard > rigid gas-permeable [RGP] > soft), fit, and length of time of wear; not associated with corneal edema. Usually asymptomatic; may have contact lens intolerance, blurred vision with glasses, loss of best spectacle-corrected visual acuity, or change in refraction (especially axis of astigmatism); corneal topography is abnormal (irregular astigmatism)

Treatment: discontinue lens wear; repeat refraction and corneal topography until stable

Corneal Transplant Failure

Early (primary)

poor tissue or surgery

Late

allograft rejection (delayed onset [at least 2 weeks]); homograft reaction

Risk factors

young age, stromal vascularization, previous graft failure, post chemical burns, inflammatory disease

Symptoms

decreased vision, redness, pain, irritation

Findings

Epithelial rejection line (‘battle’ line of host-versus-donor epithelium): occurs in 10%, often precedes more destructive rejection events

Endothelial rejection: anterior chamber reaction, keratitic precipitates, graft edema, Khodadoust rejection line (moves across cornea destroying endothelium, resulting in stromal edema)

Other findings: subepithelial infiltrates, new KP, increased IOP (trabeculitis from AC reaction)

Treatment

Endothelial rejection: IV steroids (methylprednisone 500 mg; reduces risk of subsequent rejection episodes [33% vs 67% for oral steroids]), topical steroids (40% reversal rate alone), oral steroids

Epithelial rejection or stromal infiltrates with no graft swelling: treat with topical therapy alone

Prognosis

graft survival rate for treating endothelial rejections with a single pulse of IV steroids is 90% when presents within 1 week and 67% when presents later than 1 week (probably due to irreversible damage to endothelial cells despite reversal of rejection)

Epithelial Downgrowth

Can occur following almost any intraocular surgery; increased risk with complicated surgery associated with hemorrhage, inflammation, vitreous loss, or incarcerated tissue

Surface epithelium grows through wound into eye, covering anterior segment structures

Appears as advancing line on corneal endothelium

Epithelium can cover the endothelium (leading to edema) and the angle (resulting in glaucoma); contact inhibition by healthy endothelium may inhibit this

Pathology

multilayered nonkeratinized squamous epithelium; PAS stains conjunctival goblet cells (differentiates between corneal and conjunctival epithelium) (Figure 7-16)

Figure 7-16 Epithelial downgrowth with epithelium present on corneal endothelium, angle, and iris, and into vitreous.

(From Yanoff M, Fine BS: Ocular Pathology, 5th edn, St Louis, Mosby, 2002.)

DDx of retrocorneal membrane

mesodermal dysgenesis, ICE syndrome, trauma, posterior polymorphous dystrophy, disciform keratitis (HSV or HZV), alkali burn

Diagnosis

argon laser application to surface of iris produces white burn if iris involved; helps delineate extent of epithelial membrane

Treatment

excision of epithelial membrane and involved tissue with cryotherapy to remaining corneal membrane; high-power laser ablation of entire membrane may occasionally work; complete excision is difficult

Prognosis

poor, often develop secondary glaucoma

Fibrous Ingrowth

Fibrous proliferation through wound into AC

Less progressive and destructive than epithelial downgrowth

Fibroblasts originate from episclera or corneal stroma

Graft-Versus-Host Disease (GVHD)

Ominous complication of bone marrow transplant (BMT)

3 requirements

Graft must contain immunologically competent cells

Host must possess important transplantation isoantigens lacking in graft (so host appears foreign)

Host must not be able to mount immunologic reaction against graft

Types of bone marrow transplants

Autologous: patient’s own stored marrow

Syngeneic: marrow from identical twin

Allogeneic: marrow from HLA-matched donor

Complications

Acute: hemorrhage and infection (first 100 days following BMT [period of aplasia])

Late: GVHD (T lymphocytes in transplanted marrow recognize antigens of host as foreign, become sensitized, and attack host’s organs; minor histocompatability antigens are the inciting antigens, cytotoxic T cells are the effectors)

Occurs primarily in allogeneic grafts

50% develop acute GVHD (50% mortality); 20–40% develop chronic GVHD

Acute GVHD is biggest risk factor for chronic GVHD

Findings

hemorrhagic cicatricial conjunctivitis, pseudomembranes, symblepharon, punctate keratitis, keratoconjunctivitis sicca, lagophthalmos, entropion, microvascular retinopathy (4–10%), optic neuropathy (2%; thought to be due to cyclosporine [ciclosporin], resolves with discontinuation)

Other findings

Acute GVHD: maculopapular rash on palms and soles, pruritus, GI involvement (diarrhea), elevated liver enzymes

Chronic GVHD: sclerodermatoid or lichenoid skin changes, Sjögren’s-like syndrome

Diagnosis

skin, liver, intestinal biopsy

Treatment

cyclosporine, high-dose systemic steroids; treat ocular complications

Prognosis

acute GVHD (stage 2 or higher) occurs in 12% and has a 90% mortality; chronic GVHD 10-year survival = 40%

Iridocorneal Endothelial Syndrome (ICE)

(See Ch. 10, Anterior Segment)

Multiple Endocrine Neoplasia (MEN)

MEN 1 (Werner’s syndrome)

Mapped to chromosome 11

Neoplasias of pituitary, parathyroid, and islet cells of pancreas

Findings: visual field defects from pituitary tumors

MEN 2a (Sipple’s syndrome) (AD)

Mapped to chromosome 10

Medullary thyroid carcinoma, pheochromocytoma, parathyroid adenomas

Findings: prominent corneal nerves

Pathology: thickened conjunctival nerves contain numerous Schwann cells and partially myelinated axons; thickened corneal nerves are due to an increased number of axons per nerve fiber bundle

Diagnosis: elevated calcitonin and vanillylmandelic acid

MEN 2b (Sipple-Gorlin syndrome) (AD)

Mapped to chromosome 10

Medullary thyroid carcinoma, pheochromocytoma, mucosal and GI neuromas, marfanoid habitus

Eye findings: prominent corneal nerves, conjunctival neuroma (87%), eyelid neuroma (80%), dry eye (67%), prominent perilimbal blood vessels (40%)

DDx of prominent corneal nerves: leprosy, Acanthamoeba, Down’s syndrome, neurofibromatosis, keratoconus, congenital glaucoma, Refsum’s disease, Fuchs’ corneal endothelial dystrophy, failed corneal graft, keratoconjunctivitis sicca, trauma, advanced age, ichthyosis, posterior polymorphous dystrophy

Tumors

Corneal Intraepithelial Neoplasia (CIN)

(See Conjunctiva section)

Squamous Cell Carcinoma (SCC)

(See Conjunctiva section)

Scleral Disorders

Scleritis

Inflammation of sclera

More common in females; onset age 30–60 years

>50% bilateral

Etiology

50% associated with systemic disease

Collagen vascular diseases (RA [20% of all cases of scleritis; only 3% of patients with RA develop scleritis; 75% of RA-related scleritis is bilateral], SLE, polyarteritis nodosa), vascular disease (Wegener’s granulomatosis, giant cell arteritis, Takayasu’s disease), relapsing polychondritis, sarcoidosis, ankylosing spondylitis, Reiter’s syndrome, Crohn’s disease, ulcerative colitis, infections (syphilis, TB, leprosy, HSV, HZV), gout, rosacea

Classification

Anterior: 98%

DIFFUSE (40%): most benign; widespread involvement

PATHOLOGY: sclera thickened, diffuse granulomatous inflammation of scleral collagen

NODULAR (44%): focal involvement; nodule is immobile

PATHOLOGY: zonal necrotizing granuloma, fibrinoid necrosis, chronic inflammation, fusiform thickening, immune complex deposition with complement activation; once collagen has been destroyed, inflammation recedes, uvea herniates into defect

NECROTIZING (14%): associated with life-threatening autoimmune disease (5-year mortality rate = 25%)

WITH INFLAMMATION: focal or diffuse, progressive, pain and redness; vascular sludging and occlusion; underlying blue uveal tissue may be visible giving redness a ‘violaceous’ hue; 40% lose vision; 60% have ocular complications: anterior uveitis, sclerosing keratitis, cataract, glaucoma, peripheral corneal melt, scleral thinning

WITHOUT INFLAMMATION (scleromalacia perforans): minimal symptoms, minimal injection; scleral thinning, marked ischemia; seldom perforate; females with severe rheumatoid arthritis; 8-year mortality rate = 21%

Posterior: 2%; usually unilateral; very painful

Usually no associated systemic disorder

80% have anterior scleritis

FINDINGS: thickened and inflamed posterior sclera, chorioretinal folds, amelanotic fundus mass, ON edema; may have vitritis, macular edema, limitation of motility, ptosis, proptosis, exudative RD, elevated IOP (forward shift of lens-iris diaphragm due to ciliochoroidal detachment)

B-SCAN ULTRASOUND: pocket of fluid in Tenon’s space (sclerotenonitis), T sign, thickened sclera

FA: early patchy hypofluorescence, late staining, disc leakage

CT SCAN: thickening of posterior sclera with contiguous involvement of orbital fat (T sign)

DDX: choroidal tumor, orbital pseudotumor (IOI), uveal effusion syndrome, VKH, thyroid-related ophthalmopathy, orbital tumors

Symptoms

pain, redness, photophobia

Findings

diffuse or sectoral area of deep injection (violaceous hue), tender to touch, chemosis, scleral edema; may have scleral nodule, scleral thinning, AC reaction (33%), keratitis (acute stromal keratitis, sclerosing keratitis, marginal keratolysis); chorioretinal folds and serous RD in posterior scleritis

Treatment

oral NSAID, consider oral steroids or immunosuppressive agents; treat underlying disorder; topical steroids are not effective; sub-Tenon’s steroid injection is contraindicated; may require patch graft for perforation

Complications

keratitis, cataract, uveitis, glaucoma

Wegener’s Granulomatosis

Systemic disease of necrotizing vasculitis and granulomatous inflammation involving sinuses, respiratory system, kidneys, and orbit

Males > females

Findings (60%)

nasolacrimal duct obstruction, proptosis, painful ophthalmoplegia, conjunctivitis, chemosis, KCS, episcleritis, necrotizing scleritis (most common type of ocular involvement), keratitis, cotton-wool spots, arterial narrowing, venous tortuosity, choroidal thickening, CME, CRAO, optic nerve involvement

Other findings

upper respiratory tract (hemoptysis), renal failure (major cause of death), hemorrhagic dermatitis, cerebral vasculitis, weight loss, peripheral neuropathy, fever, arthralgia, saddle nose (destruction of nasal bones)

Diagnosis

C-ANCA positive in 67%

Treatment

systemic steroids and immunosuppressives (cyclophosphamide)

Complications

fatal if untreated

Takayasu’s Disease

Narrowing of large branches of aorta

Diminished pulsations in upper extremities

Decreased blood pressure in upper extremities, increased BP in lower extremities

Findings

scleritis, amaurosis fugax, ocular ischemia, AION

Polyarteritis Nodosa

Systemic vasculitis affecting medium-sized and small arteries

Males > females

Findings

necrotizing sclerokeratitis, vascular occlusions, ischemic optic neuropathy, rarely aneurysms of retinal vessels

Other findings

kidneys (nephritic or nephrotic syndrome, hypertension, renal failure), heart (MI, angina, pericarditis), intestines (pain, infarction), arthritis, peripheral neuropathy

Relapsing Polychondritis

Multisystem disorder characterized by recurrent episodes of inflammation in cartilaginous tissues throughout body

Findings (60%)

episcleritis, scleritis, iritis, conjunctivitis, keratoconjunctivitis sicca (KCS), exudative RD, optic neuritis, proptosis, CN 6 palsies

Other findings

migratory polyarthritis, fever, diffuse inflammation of cartilage (nose, ear, trachea, larynx)

Treatment

topical or systemic steroids; dapsone

Surgery

Penetrating Keratoplasty (PK; PKP)

Full-thickness corneal graft / transplant

Most common indications

bullous keratopathy (pseudophakic, aphakic), keratoconus, graft failure, corneal scar; Peter’s anomaly (children)

Success rate

90% of grafts are clear at 1 year (>90% for keratoconus; 65% for HSV)

Complications

rejection (20%), failure, glaucoma, suprachoroidal or expulsive hemorrhage, endophthalmitis, recurrence of pathology

Collaborative Corneal Transplant Treatment Study (CCTS)

ABO blood type incompatability is a possible risk factor for rejection

HLA matching is not cost-effective or advantageous

High-risk status: vascularization of cornea in 2 quadrants, history of previous graft rejection, glaucoma, extensive PAS, traumatic or hereditary ocular surface disorders

Donor screening

Contraindications for donor corneas: septicemia, lymphoma or leukemia, systemic malignancy with ocular metastasis, anterior segment tumors (choroidal melanoma is not a contraindication), Creutzfeldt-Jakob disease, rabies, subacute sclerosing panencephalitis, PML, HIV, hepatitis B and C (neither HIV nor hepatitis C has ever been transmitted)

Tissue preservation

4°C moist chamber: use within 48 hours

M-K medium (McCarey-Kaufman): TC-199 medium with dextran (5% concentration) and gentamicin stored at 4°C; use within 48 hours

Chondroitin sulfate: acts as antioxidant and membrane growth factor

K-Sol (Kaufman): chondroitin sulfate in TC-199 at 4°C; discontinued

Corneal storage media (CSM): from Minnesota Lions Eye Bank researchers plus mercaptoethanol (antioxidant) and chondroitin sulfate; discontinued with introduction of dexsol and optisol

Dexsol: minimal essential medium with chondroitin sulfate and dextran 1% (osmotic agent to keep cornea thin)

Optisol: hybrid of K-Sol, Dexsol, and CSM, plus vitamins, amino acids, and antioxidants; as effective as dexsol but keeps cornea thinner

Many media contain pH indicators that change color with a change in pH (i.e. microbial contamination)

Lamellar Keratoplasty (ALK, DALK)

Partial or full-thickness stromal graft composed of epithelium, Bowman’s membrane, and stroma. Anterior lamellar keratoplasty (ALK) involves a stromal dissection, while deep anterior lamellar keratoplasty (DALK) entails replacement of stromal tissue down to the level of Descemet’s membrane. The dissection can be performed manually, with an air bubble or viscoelastic

Indications

stromal pathology (scar, dystrophy) and keratoconus (DALK)

Contraindications

corneal endothelial dysfunction

Complications

graft rejection, suture-related complications, and interface opacification can occur with both procedures; intraoperative Descemet’s membrane tear or perforation can occur with DALK requiring conversion to penetrating keratoplasty.

Endothelial Keratoplasty (EK)

Descemet’s Stripping and Automated Endothelial Keratoplasty (DSAEK)

Endothelium is manually stripped and replaced by donor lenticule composed of endothelium, Descemet’s membrane, and thin layer of stroma prepared with a microkeratome

Indications

corneal edema due to Fuchs’ dystrophy and bullous keratopathy

Complications

endothelial rejection, lenticule separation or displacement

Alternatives

Descemet’s Membrane Endothelial Keratoplasty (DMEK; requires peripheral iridotomy / iridectomy), Descemet’s Membrane and Automated Endothelial Keratoplasty (DMAEK; lenticule has peripheral ring of stroma) require smaller incision and may have better vision

Keratophakia

Donor lenticule is placed between the cornea and a microkeratome created lamellar section to correct aphakia

Contraindications

thinned corneas, infants, glaucoma

Keratomileusis

Lamellar section is removed, frozen, shaped on a cryolathe, then replaced in stromal bed to correct myopia or hyperopia. Donor lenticule can be used instead (Figure 7-17)

Figure 7-17 Keratomileusis. In a myopic keratomileusis, a corneal button is raised using a microkeratome, and it is reshaped using a cryolathe (upper part). When the button is replaced, the central cornea is flattened (lower part).

(From Chang SW, Azar DT: Automated and manual lamellar surgical procedures and epikeratoplasty. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Contraindications

glaucoma

Epikeratophakia (Epikeratoplasty)

Epithelium is removed and a lathed donor lenticule is placed to correct myopia or hyperopia (Figure 7-18)

Figure 7-18 Epikeratoplasty. A preshaped donor lenticule is sutured to the recipient stromal bed to correct myopia and hyperopia.

(From Chang SW, Azar DT: Automated and manual lamellar surgical procedures and epikeratoplasty. In Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)

Can be performed in children; reversible

Contraindications

blepharitis, dry eye, lagophthalmos

Pathology

2 Bowman’s membranes (donor lenticule and patient)

Astigmatic Keratotomy (AK)

99% depth arcuate or straight incisions typically placed at the 7 or 8 mm optical zone (OZ) to correct astigmatism

Various nomograms exist (i.e. Lindstrom ARC-T)

Do not make arcuate incisions >90° (decreased efficacy, increased instability)

When combined with RK, do not cross incisions (creates wound gape and instability)

Limbal / corneal relaxing incisions (LRI / CRI) are performed at 10–12 mm OZ, usually at time of cataract surgery with preset diamond knife (500–600 µm depth)

Radial Keratotomy (RK)

Deep radial corneal incisions to correct low to moderate myopia

Effect dependent on number of incisions, depth of incisions, size of optical zone, patient age

Number of incisions: the greater the number of incisions, the greater the effect; never use more than 8 incisions (additional incisions have limited effect and cause greater destabilization of the cornea)

Incision depth: the deeper the incision, the greater the effect; diamond knife is set at 100% of thinnest pachymetry measurement (usually paracentral inferotemporal region; temporal < inferior < nasal < superior)

Optical zone: the smaller the diameter of the OZ (the longer the incision), the greater the effect; do not make OZ <3 mm (visual aberrations [starburst])

Patient age: the older the patient, the greater the effect

Patient sex: greater effect in males than in females

Technique

American (downhill cut [toward limbus], safer but shallower) vs Russian (uphill cut [toward central cornea], deeper but risk of invading OZ); combined technique with special knife gives deep cut with safety

Complications

undercorrection or overcorrection, perforation, infection, scarring, irregular astigmatism, progressive hyperopia (in PERK study, 43% had ≥1.00 D of hyperopia after 10 years), glare / starburst, fluctuating vision

Results

85% achieved 20/40 or better vision after initial procedure; 96% achieved 20/40 or better after enhancement, 85% achieved 20/25 or better after enhancement

Photorefractive Keratectomy (PRK)

Laser ablation of corneal surface to correct myopia, hyperopia, and astigmatism

Excimer (excited dimer) laser

argon-fluoride (wavelength = 193 nm; far ultraviolet), energy = 64 eV

Functions as a ‘cold’ laser (breaks molecular bonds to ablate tissue; no thermal damage)

Each pulse removes approximately 0.25 µm of corneal tissue

Depth of ablation is related to diameter of optical zone and amount of intended correction

Munnerlyn equation

depth = (refractive error/3) × OZ²

Example: 12 µm for 6 mm OZ and 1 D of myopia

Advantages of PRK

precise removal of tissue, minimal adjacent tissue damage

Disadvantages of PRK

involves visual axis, risk of haze / scarring, regression, requires removal of epithelium

Contraindications

collagen vascular, autoimmune, or immunodeficiency disorders; pregnancy; corneal ectasia; keloid formation; isotretinoin (Accutane), amiodarone, sumatriptan (Imitrex)

Cautions

unstable refraction (change of >0.5 D/year), systemic diseases that affect wound healing (diabetes, atopy, connective tissue diseases, immunocompromised status), herpes keratitis (HSV or HZV), ocular inflammation (keratitis, acne rosacea, pannus that extends into visual axis)

Complications

undercorrection or overcorrection, haze / scarring, delayed reepithelialization, sterile infiltrates, infection, decentered ablation, central island, irregular astigmatism, keratectasia, regression, glare, halos, dry eye, glaucoma or cataract (from steroids)

Corneal haze: risk and severity increases with deeper ablations and postoperative ultraviolet (UV) radiation exposure; results in decreased vision with regression of effect. Oral vitamin C 1000 mg/day for 1 week before surgery and 2 weeks postoperatively, and avoidance of UV exposure may help prevent haze

Treatment of complications

Enhancements: it is recommended to wait at least 3 months or until the refraction and corneal topography are stable before performing an enhancement for overcorrection or undercorrection

Haze: treat with topical steroids; consider application of mitomycin C 0.02% for 2 minutes along with scar débridement with either a diamond burr or a superficial excimer laser treatment (PTK). Once the haze is reduced, the refraction can change dramatically, so do not treat residual refractive error at time of haze removal

Irregular astigmatism: rigid gas-permeable contact lens, wavefront-guided retreatment

Laser in Situ Keratomileusis (LASIK)

Combination of keratomileusis and excimer laser ablation to correct myopia, hyperopia, and astigmatism

Corneal flap created with mechanical or laser microkeratome and laser ablation performed on underlying stromal bed

Advantages of LASIK

more rapid healing, less discomfort, less risk of haze, less postoperative medications

Disadvantages of LASIK

flap complications

Complications

Intraoperative: flap complication (buttonhole, incomplete, or irregular flap, free cap) epithelial abrasion or sloughing, programming error, decentered ablation.

Immediate postoperative: diffuse lamellar keratitis (DLK, sands of Sahara), central toxic keratopathy, infection, flap dislocation, flap striae, epithelial ingrowth, central island, irregular astigmatism, dry eye, undercorrection or overcorrection, night vision problems (glare, halos)

Delayed postoperative: dry eye, late DLK, late flap slip, undercorrection or overcorrection, keratectasia, photophobia (from laser keratome, 1–3 weeks to 3 months postop, treat with topical steroids)

Treatment of complications

Buttonhole (increased risk with steep corneas), incomplete or irregular flap: replace flap, do not perform ablation; when cornea stabilizes, either cut a new flap or perform surface ablation (PRK / PTK)

Free cap (increased risk in cases of flat corneas): place free cap in moisture chamber epithelial side down, perform ablation, then replace cap and let dry

Epithelial slough or corneal abrasion: increased risk with certain microkeratomes and in eyes with epithelial basement membrane dystrophy; increases risk of developing DLK and epithelial ingrowth

Treat with bandage contact lens and close follow-up. If large defect occurs in first eye, consider postponing treatment of second eye

Flap striae or flap dislocation: replace flap and stretch; consider use of epithelial débridement, hypotonic saline or sterile water, ironing with a warm spatula, or suturing (interrupted radials or antitorque)

DLK: inflammation within flap interface; etiology often unknown; increased risk with epithelial defect. Late DLK may result from increased intraocular pressure, epithelial defect, and cornea ulcer

Treat with frequent topical steroids for grades I and II, and flap lifting and interface irrigation for grades III and IV; consider a short pulse of oral steroids

Central toxic keratopathy: noninflammatory central corneal opacity and hyperopic shift; appears on postop day 3–5, usually preceded by DLK. No treatment. Spontaneously resolves in 2–18 months. May also occur after PRK

Epithelial ingrowth: nests of epithelium growing under the flap; more common in eyes with epithelial basement membrane dystrophy and after enhancements. Ingrowth that is progressive or affects the vision is treated with flap lifting and débridement of the stromal bed and flap undersurface. Consider radial sutures if ingrowth recurs, Consider Nd : YAG laser treatment

Irregular ablation (decentered, irregular astigmatism): requires custom or wavefront-guided retreatment

Corneal ectasia (keratectasia): treatment of eyes with a preexisting ectasia (keratoconus, forme fruste keratoconus, pellucid marginal degeneration) or excessive depth of ablation in normal corneas (residual stromal depth <250 µm) can result in progressive myopic astigmatism and corneal ectasia. Treat with corneal collagen crosslinking to halt progression. A rigid gas-permeable contact lens can help with visual improvement, but will not stop progression. Consider Intacs to improve the shape of the cornea, or penetrating keratoplasty for severe cases.

Dry eye: can worsen postoperatively if untreated prior to surgery; can also occur in patients without pre-existing dry eye. Superior hinged flap may cause greater dryness than is caused by nasal hinged flap. Treat with frequent lubrication; consider punctal occlusion and topical cyclosporine

Glare / halos: often due to residual refractive error. The role of scotopic pupil size as a contributing factor is controversial (may have been a risk with older laser ablations, but is not a risk factor with modern laser ablations). Treatment options include pharmacologic miosis (Alphagan-P or iilocarpine), or retreatment with larger optical zone or blend zone

Infectious keratitis: uncommon but serious complication; most common organisms are Gram-positive cocci and atypical Mycobacteria. Suspected infection requires lifting flap and culturing; treat with fortified topical antibiotics (vancomycin and amikacin); may require flap amputation

Laser-Assisted Epithelial Keratomileusis (LASEK)

Variation of PRK; epithelial flap is created with alcohol, excimer laser is applied, and epithelial flap is replaced

Advantages of LASEK

may have less risk of haze than PRK

Disadvantages of LASEK

slower visual recoevery than with PRK.

Complications

same as with PRK. undercorrection or overcorrection, haze / scarring, delayed reepithelialization, infection, decentered ablation, central island, irregular astigmatism, regression, glare / halos, dry eye, stromal incursion (with mechanical flap device)

Risk of haze can be reduced with oral vitamin C and avoidance of UV exposure

Phototherapeutic Keratectomy (PTK)

Use of excimer laser to ablate corneal pathology limited to anterior of cornea

Indications

superficial scars, dystrophies, irregularities, residual band keratopathy, recurrent erosions

Can use confocal microscopy to determine depth of pathology

Complications

recurrence of pathology, reactivation of HSV, induced hyperopia or irregular astigmatism

Intracorneal Inlays

A thin, contact lens-like, implant placed in the central optical zone beneath a corneal flap to correct myopia, hyperopia, astigmatism, or presbyopia without removing corneal tissue

Potential technologies: implant thickness and shape alters the corneal curvature, implant has power, or implant acts as a pinhole.

Advantages

reversible, adjustable, no removal of tissue

Complications

undercorrection or overcorrection, irregular astigmatism, glare, halos, flap striae, epithelial ingrowth, DLK, infection, implant decentration or extrusion

Intrastromal Corneal Ring Segments (Intacs)

Ring segment implants placed into peripheral corneal channels outside the visual axis to correct low to moderate myopia. Implants flatten the cornea without cutting or removing tissue from the central optical zone. Also used to reshape corneas with keratoconus or post-LASIK ectasia (Figure 7-19)

Figure 7-19 Slit-lamp photograph of the intrastromal corneal ring segments in position in patient’s cornea.

(Courtesy of Mr. Thomas Loarie. From Friedman NJ, Husain SE, Kohnen T et al: Investigational refractive procedures. In: Yanoff M, Duker JS [eds]: Ophthalmology, London, Mosby, 1999.)