INFECTIOUS DISEASE

ruptured bullae with patching or BSCL. Common cause for transplant. If cataract is visually significant, consider triple procedure (PK/cataract extraction/IOL) if pachymetry >620 mm centrally (normally about 520 mm) or cell count <1200. However, if patient is asymptomatic without edema or morning symptoms, go ahead with best phacoemulsification through scleral tunnel, with generous use of viscoelastic.

Posterior polymorphous membrane dystrophy (PPMD): autosomal dominant or recessive, chromosome 20q11-cen (like CHED type 2) defect of endothelial cells that behave like epithelial cells (similar to ICE syndrome except PPMD is bilateral and congenital). ‘‘Nests’’ of endothelial cells look like ‘‘snail tracks’’ with vesicular gray lesions and opacities in Descemet’s membrane and on endothelium. Onset is at birth to age 1; bilateral but asymmetric, usually asymptomatic. Openor closed-angle glaucoma seen in 15% of cases. Epithelial-like cells in endothelium have desmosomes, microvilli, and keratin staining. VA usually normal; rarely requires PK but can recur after graft.

Infectious Disease

ACANTHAMOEBA Ubiquitous protozoan found especially in stagnant, contaminated water, nonsterile contact lens solution, and hot tubs. Typically inoculated, with corneal trauma causing a keratitis with pain out of proportion to the corneal ulcer, PEE or epithelial irregularity (may mimic HSV), multifocal stromal infiltrates and late ring infiltrate, radial neuritis with prominent corneal nerves, and hypoesthesia. Can also cause meningitis from diving into contaminated water, with transmission through the cribriform plate.

Usually first treated as a bacterial keratitis, but when it is suspected, do culture or biopsy and stain with H & E and periodic acid. Look for mobile trophozoite (active) or double-walled cysts (inactive). Can also stain with Calcoflour white (not clinically practical, as fluorescent microscope is needed to see stain binding to cell wall; also positive for fungi). Culture cornea and CL case or lenses; may see tracks of the trophozoites on Escherichia coli nonnutrient agar. May need corneal biopsy at border of infiltrate and normal tissue.

Treat with debridement, oral ketoconazole, polyhexamethylene biguanide (PHMB) 0.02% (made from swimming pool cleaner), acridene orange, 0.01% propamidine (Brolene; available in Europe), or Neosporin. Requires months of topical treatment, and often requires systemic treatment. May require palliative PK if infection is nearing the limbus or to debulk infectious burden; otherwise, wait 6 months after infection clears for PK.

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ADENOVIRUS Predominantly follicular conjunctivitis with preauricular lymphadenopathy in 50% of cases. May have subconjunctival hemorrhage or membranes.

Epidemic keratoconjunctivitis (EKC): serotypes 8, 11, and 19 (mnemonic: 8 þ 11 ¼ 19); symptoms peak 5 to 7 days; mixed papillary and follicular conjunctivitis. Progresses from diffuse PEE, to diffuse PEK (day 3), to deep focal PEK (day 7), to subepithelial infiltrates (day 15), and finally to gray epithelial infiltrates (day 17). Give supportive care, and avoid steroids, as prolonged taper is often necessary to prevent the recurrence of subepithelial infiltrates. The developing world is especially prone to pandemics of acute follicular conjunctivitis—set up mass screening clinics utilizing ‘‘no touch’’ exam techniques and provide supportive care.

Pharyngeal conjunctival fever (PCF): adenovirus serotypes 3, 4, 7 (mnemonic: 3 þ 4 ¼ 7); EKC with fever and pharyngitis. Provide supportive treatment.

BACTERIAL KERATITIS Predisposed by trauma, preexisting corneal disease, eyelid abnormalities, steroids, CLW (extended CLW has 5 risk of daily CLW, which has 2 greater risk than rigid gas-permeable contact lens wear) mostly from poor lens case hygiene, anterior segment surgery (RK and AK have 0.25 to 0.70% incidence, photorefractive keratectomy 1.2%), and smoking. Most cases occur from staphylococcus, streptococcus, or Pseudomonas associated with CLW. May also be from:

Actinomyces: filamentous bacteria, obligate, anaerobic, not acid-fast. Grows on vitamin K–dependent blood agar; may also cause canaliculitis. Sensitive to penicillin.

Atypical mycobacterium: indolent ‘‘cracked windshield’’ infiltrate associated with trauma or foreign body. Grows on acid-fast stain and Lowenstein-Jensen medium. Treat with amikacin plus erythromycin.

Interstitial crystalline keratopathy (ICK): colonization along corneal lamella from Streptococcus viridans with crystalline or feathery appearance; usually occurs in a corneal graft while patient is on steroids or after LASIK.

Moraxella: gram-negative diplobacilli; dumbell shaped with flat ends. Grows on Lo¨ffler’s medium or 5% CO2 at 37 C blood agar; may cause opportunistic infection in alcoholic or debilitated patients.

Nocardia: typically from trauma or foreign body; mimics fungal keratitis. Treat with Polytrim.

Sterile infiltrates associated with CLW: small multiple infiltrates, usually peripheral, with intact epithelium, no cell in AC, minimum pain.

CHLAMYDIA Cause of trachoma (serotypes A–C; mnemonic: trAChoma), adult inclusion conjunctiva (types D–K), and lymphogranuloma

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venerum (types L1–L3). Obligate intracellular organism that demonstrates intracytoplasmic inclusion bodies.

Trachoma: a major cause of preventable blindness in the world from chronic conjunctival reinfections with upper lid scarring, entropion, secondary bacterial keratitis, and eventual corneal scarring. Endemic in the Middle East and spread by houseflies and fomites.

Diagnosis made by two of these: conjunctiva follicles on superior tarsus, limbal follicles, superior pannus, Herbert’s pits (scarred remnants of involuted limbal follicles), Arlt’s line (linear conjunctival scar across superior tarsus). Culture to confirm diagnosis (need to scrape and break cells open).

Staging: MacCallan staging describes course—immature follicles, mature follicles, conjunctival scarring, and inactive. World Health Organization (WHO) staging describes severity based on five signs—conjunctival follicles, diffuse conjunctival inflammation, tarsal conjunctival scarring, trichiasis, and corneal opacification.

Treat with erythromycin or tetracycline 500 mg tid for 3 weeks and topical. Large populations can prevent infection by washing hands and face at least once a day (do not even need soap).

Adult inclusion conjunctivitis (AIC): sexually active direct or indirect contact with follicular conjunctivitis, superior micropannus, and no membranes, unlike neonatal chlamydia infection. Course waxes and wanes for 1 to 2 weeks after exposure. Diagnose with chlamydia immunofluorescence (take sample before applying fluorescein), culture, or Giemsa stain. Treat with macrolides (e.g., Zithromax 1 g singledose or erythromycin) or tetracycline for 3 weeks. Considered a sexually transmitted disease; thus, rule out gonorrhea and syphilis, and recommend treatment for partner.

CONJUNCTIVITIS, BACTERIAL Constitutes only 5% of conjunctivitis cases; papillary reaction with purulent discharge, slow onset. Most cases resolve spontaneously; patients usually have other risk factors (immunocompromised, trauma, etc.).

CONJUNCTIVITIS, NEONATAL, OPHTHALMIA NEONATORUM Gram stain and culture to confirm organism.

Chemical: onset within 24 hours of use of irritating agent, usually silver nitrate; few to no polymorphonuclear leukocytes (PMNs).

Bacterial: usually Streptococcus viridans. Treat with topical antibiotics except N. gonorrhoeae (rare, but may have disseminated infection such as proctitis, rhinitis, or meningitis); also treat with IV antibiotics.

Chlamydial: no follicles but may have membranes, unlike adult inclusion conjunctivitis. Intracytoplasmic inclusion bodies seen on Giemsa stain. Treat with erythromycin topical and PO for pneumonia usually 3 to 13 weeks later (not covered by silver nitrate).

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Herpetic: onset within 2 weeks after birth if infant was inoculated during delivery. Use IV acyclovir to treat concurrent pneumonitis, and use topical antiviral ointment or drops. No follicles are present, as infants are immunologically incompetent.

DEMODEX Normal commensal mites on hair follicles and in meibomian glands. Ubiquitous; causes itchy eyes, may see ‘‘sleeves’’ on lashes. Treat with lid scrubs, metronidazole topical gel.

FUNGAL KERATITIS Predisposed by trauma, foreign body (especially vegetable matter), immunocompromised, CLW. Indolent, severe pain when established; infiltrate characterized by rough textures, elevated borders, feathery margins, satellite lesions, descemetatrophic, endothelial migration. In northern United States, most likely Candida (mnemonic: near Canada); in southern United States, most likely Fusarium.

Culture on Sabaroud’s medium: 54% positive culture in 24 hours, 83% in 72 hours, 97% in 1 week (thus, hold culture at least a week even if there is negative initial growth).

Treat based on initial potassium hydroxide (KOH) preparation or fungal stain, and modify depending on culture results:

Filamentous hyphae (often Fusarium, aspergillus): treat initially with topical natamycin and oral fluconazole. May also use itraconazole (suspend 100 mg tablet in 10 cc saline) or topical Betadine.

Yeast or pseudohyphae (often Candida): treat initially with amphotericin B 0.1% or natamycin plus fluconazole oral 400 mg load.

HERPES SIMPLEX VIRUS (HSV) The leading cause of corneal blindness; caused by DNA virus that after primary infection remains latent in the trigeminal ganglion (and maybe in cornea). Pathology shows intranuclear inclusion bodies (Lipschu¨tz bodies or Cowdry type A).

Primary infection presents as unilateral follicular blepharoconjunctivitis with membranes, vesicles, and preauricular lymphadenopathy. Two thirds of cases have PEK or dendrites; <10% develop stromal keratitis or uveitis. Ten percent are bilateral; consider work-up for immunosuppressed or atopic conditions if bilateral. Treat cornea prophylactically with drops even if infection is confined to the conjunctiva.

Recurrent infection presents with dendritic keratitis, which are true ulcerations rather than epithelial swelling and elevation, as seen in HZV (active viral replication in epithelial cells produce sloughing and stain well with fluorescein, and epithelial cells neighboring the dendrite are full of virus and stain well with rose Bengal). May also have geographic ulcers, disciform stromal keratitis, necrotizing keratitis with destruction of Descemet’s membrane (may have a foreign

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body–like reaction to Descemet’s), ring KP, iridocyclitis, iris atrophy with transillumination defects, and increased IOP (trabeculitis). ‘‘Backdoor’’ infection does not need primary ocular infection (latent reactiviation after primary V2).

HSV may be implicated in ICE, Posner-Schlossman syndrome, and Fuchs’ HIC.

Epithelial HSV: geographic defect or dendritic ulcer. Treat with Viroptic 9 per day (use limited by its epithelial toxicity), acyclovir 400 mg 5 per day; consider epithelial debridement. If the cornea becomes trophic (nonhealing), stop topicals, change to orals, lubricate, and consider BSCL.

Stromal HSV: immune reaction to viral antigens, not active viral replication, with intact epithelium, stromal infiltrate, and edema; often see ring KP. Treat with steroids; consider prophylactic antivirals, PTK for corneal scarring (HSV may reactivate).

Herpetic Eye Disease Study (HEDS): use acyclovir 400 mg (do not need Viroptic) bid for 1 year for those with recurrent stromal keratitis. Hold steroids until epithelial process resolved. Three arms of study found that:

Acyclovir is not proven for stromal keratitis (but is often used) and has a benefit for iritis.

Topical steroids increase resolution of stromal keratitis, decrease progressive and persistent keratouveitis by 68%, but no change seen in visual outcome at 6 months compared with controls.

Acyclovir for keratitis does not prevent subsequent stromal keratitis or iritis.

HERPES ZOSTER VIRUS (HZV), VARICELLA ZOSTER VIRUS (VZV) DNA poxvirus that causes chickenpox, shingles, and herpes zoster ophthalmicus. In all body dermatomes, affects 24% of adults, with pitting scars. Ocular involvement is possible with trigeminal nerve infection. Hutchinson’s sign (vesicle at side of the tip of nose) indicates that nasociliary nerve is involved and ocular infection is likely. Unusual in young patients; thus, rule out malignancy or immunosuppression. Recurrent disease is common.

Epithelial infection demonstrates raised dendrites that stain best with rose Bengal (swollen and heaped up in HZV versus sloughing in HSV), corneal hypoesthesia (more pronounced than in HSV with greater risk for neurotrophic cornea). Disciform keratitis is often bilateral. May have iritis with increased IOP from trabeculitis and prominent iris atrophy. May also cause acute retinal necrosis (ARN) and Ramsay Hunt syndrome (CN VII palsy). May present with ocular symptoms without skin rash.

Treat with oral acyclovir (not topicals) 800 mg 5 times per day (higher dosage than for HSV) or Famvir 500 mg 3 times per day, or IV if

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116 CORNEA AND CONJUNCTIVA

immunosuppressed. Disciform keratitis and iritis are treated with topical steroids. Prednisone decreases postherpetic neuralgia.

Vaccination for HZV for those not previously exposed: single dose age 1 to 12 years old or two doses 4 to 8 weeks apart if over 12 years old; contraindicated in pregnancy, and no salicylates within 6 weeks (risk of Reye’s syndrome).

HUMAN PAPILLOMA VIRUS HPV (types 16 and 19) causes papilloma. Treat with observation, cryotherapy, excision with minimal manipulation, intralesional alpha-interferon, or oral cimetidine. Sessile variant in adults, usually single, at the limbus.

INTERSTITIAL KERATITIS (IK) Stromal inflammation and vascularization with later ghost vessels and scarring.

Leprosy (Hansen’s disease): may cause neurotropic keratitis or peripheral IK. Treat with dapsone or thalidomide. Two types:

Lepromatous: organism grows at room temperature; thus, anterior eye (corneal scarring), tip of nose, and skin, more affected.

Tuberculoid: grows at higher temperature; thus, internal organs affected.

Syphilis: interstitial keratitis from inflammatory response to treponemal antigen; patients typically present at age 7 to 17. Eighty percent are bilateral, and most cases are congenital infection or rarely acquired (60% of these are unilateral). Classic Hutchinson’s triad if infected in utero: IK, notched incisors, and deafness. May also have anterior uveitis, glaucoma, saddle nose, saber shins, and rhagades (linear scars around the mouth). IK typically presents as a painful red eye as a child with corneal edema and vascular ‘‘salmon patch’’ for weeks to months (patient may give a history that he or she had to stay in a dark room for several weeks), which then resolves; usually see only ghost vessels thereafter. Whenever syphilis is diagnosed for the first time, it needs to be treated with penicillin IV for 10 days. Microhemagglutination— Treponema pallidum (MHA-TP) remains positive forever; rapid plasma reagin (RPR) is positive only with disease activity.

Tuberculosis: unilateral, sectoral, peripheral IK

LOA LOA Mango fly (Chrysops genus) that has subcutaneous or subconjunctival migration.

MORAXELLA Classically causes angular blepharitis, but also conjunctivitis and keratitis. Slow-growing aerobic bacterium that grows best in blood agar, 5 to 10% CO2 at 37 C.

NEISSERIA GONORRHOEAE Hyperacute onset of conjunctivitis or keratitis; can penetrate corneal epithelium. Treat with topical and PO antibiotics. Also treat for chlamydia.

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