194 UVEAL TRACT AND OCULAR INFLAMMATION

and is active against cysts, but typically use triple therapy (cannot rid cysts):

Pyrimethamine: 150 mg load, then 25 mg qid for 6 weeks. Check CBC weekly for bone marrow suppression.

Sulfadiazine: 4 g load, then 1 g qid for 6 weeks. May use Bactrim as substitute.

Folinic acid: 5 mg po qid. Leucovorin rescue to prevent megaloblastic anemia, as the protozoan cannot import folate and thus makes its own.

If macula-threatening, add clindamycin 300 mg qid (watch for pseudomembranous colitis) and prednisone 80–100 mg (avoid depot injection).

WHIPPLE’S RETINITIS Systemic malabsorption syndrome caused by Tropheryma whippelii (corynebacterium), seen in 40to 70-year-old patients with anterior or posterior uveitis. May have vitreous cells, pars plana exudates, cotton wool spots (CWS), retinal vasculitis, papilledema, nystagmus, gaze palsy, external ophthalmoplegia, dementia, ataxia, and arthritis. Diagnose with jejunal biopsy, vitreous biopsy to see periodic acid Schiff stained macrophages. Differential diagnosis: large cell lymphoma and sarcoidosis. Treat with tetracycline or penicillin.

Panuveitis/Diffuse Uveitis

General: Panuveitis and diffuse uveitis represent 18% of all cases of uveitis and have the signs and symptoms of any of the previously mentioned uveitic diseases. Technically, panuveitis is an inflammation that involves three noncontiguous ocular tissues.

PANUVEITIS, GRANULOMATOUS WITH LOCAL OCULAR DISEASE

Infectious: toxoplasmosis, toxocariasis, ARN/BARN, and ophthalmomyiasis (consider toxocara ELISA, toxoplasma serology)

Autoimmune: sympathetic ophthalmia, pars planitis, birdshot retinochoroidopathy, phacoantigenic, Fuchs’ HIC, and masquerade (consider history of injury, vitiligo, fluorescein angiography, and ultrasound)

Masquerade: intraocular lymphoma (consider thick smear, VDRL, FTA-Abs, toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex [TORCH], jejunal biopsy, toxoplasma titers, Lyme serology, HIV ELISA, and measles titer)

PANUVEITIS, GRANULOMATOUS WITH SYSTEMIC DISEASE

Infectious: HSV, tuberculosis, toxoplasmosis, helminthic, coccidiomycosis, sporotrichosis, brucellosis, cryptococcal, and Kawasaki disease

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

(consider tuberculosis skin test, chest x-ray, Toxocara titer, Toxoplasma titer, eosinophils, Brucella serology, and vitreous biopsy for fungal cultures)

Autoimmune: sarcoidosis, VKH, and amyloid (consider ACE, calcium, chest x-ray, gallium scan, anergy, conjunctival biopsy, exam for poliosis, vitiligo, and hearing problems)

Masquerade: candidiasis

PANUVEITIS, NONGRANULOMATOUS WITH LOCAL DISEASE

Infectious: ARN/BARN, endophthalmitis from surgery, injury, and endogenous (consider AC to vitreous cultures, CH50, and CIC)

Autoimmune: birdshot retinochoroidopathy, MCP, subretinal fibrosis and panuveitis, Fuchs’HIC, pars planitis, idiopathic senile vitritis, and lens-induced uveitis (consider HLA–A29, S antigen, brain CT, and EBV titers)

Masquerade: intraocular lymphoma and leukemia (consider x-ray for IOFB)

PANUVEITIS, NONGRANULOMATOUS WITH SYSTEMIC DISEASE

Infectious: tuberculosis, syphilis, Lyme disease, HSV-2, brucellosis, and giardiasis (consider VDRL, FTA-Abs, anergy panel, Lyme serology, chest x-ray, tuberculosis skin test, and giardia in stool)

Autoimmune: PAN and Behc¸et’s syndrome (consider eosinophils, CIC, C3, C4, RF, ANA, ESR, ANCA, serum lysozyme, 1-acid glycoprotein, and properdin factor B)

Masquerade: intraocular lymphoma and leukemia (consider CBC)

IDIOPATHIC Most cases (45%) are of an unknown cause, with negative work-up.

BEHC¸ ET’S Causes 10% of panuveitis from an occlusive vasculitis secondary to immune complex deposition. Usually presents in third decade. Leading cause of acquired blindness in Japan and Turkey, with an immunologic predisposition along the old Silk Road trading routes. Associated with HLA B51, the same region that codes for immune response, circulating immune complexes, and neutrophil diapodesis.

20% of patients present first to an ophthalmologist, often with explosive bilateral nonsimultaneous panuveitis; usually acute, but may be chronic, may have an evanescent, shifting hypopyon. May also present with a white-eye and posterior vasculitis (no isolated vitritis). Retinal veins are affected more than arteries, and the primary posterior presentation is BRVO from venous engorgement. ‘‘Cut-off’’ sign from obliterative vasculitis. Characterized by hemorrhage/ exudate, papilledema, and frosted branch angiitis. English walnuts may precipitate inflammation.

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

196 UVEAL TRACT AND OCULAR INFLAMMATION

Chronic relapsing course over 10 years that waxes and wanes. Chronic disease shows decreased anterior attacks, more retinal pathology; may look RP-like, with narrow, sheathed vessels and severe chorioretinal atrophy with RPE alterations. May have capillary dropout, macular ischemia, and NV.

Four major diagnostic criteria:

Aphthous oral ulcers (98%): especially hard palate and uvula

Genital ulcers

Erythema nodosum (70%): tender, raised skin lesions

Uveitis

Minor criteria: arthritis (52%; seen especially in Japan, usually the knee joint), epididymitis, intestinal involvement, vascular occlusions (8%; ‘‘angio-Behc¸et’s’’; also aneurysms, thrombus, and thrombophlebitis in 10% of cases), neurologic complications (10% have CN palsies, psychiatric disorders, vertigo, or hearing loss similar to VKH). Also cutaneous hypersensitivity (pathergy), developing a lesion with skin prick (ask about previous blood draws, shaving lesions). Acneiform lesions (58%; may be complicated by steroid use).

Differentiate from other posterior uveitis: sarcoidosis (more free to behave as it will, less explosive, indolent), venulitis (not as occlusive), and viral retinitis (larger, progressive coalescence of retinal whitening)

Treatment: immunosuppression with systemic steroids initially, then steroid sparing agents (e.g., Cytoxan, chlorambucil, cyclosporin). Consider PRP for NV.

SARCOIDOSIS Cause of 21% of panuveitis. Autoimmune, noncaseating, multisystem granulomatous inflammation that is a type 4 hypersensitivity (T cell reaction). Ocular disease may precede the systemic disease up to 7 years, and course usually runs 2 to 10 years. Thirty percent of patients with systemic disease have ocular involvement, with uveitis, lacrimal infiltration, conjunctival nodules, interstitial keratitis, or erythema nodosum.

Usually presents with iridocyclitis, mutton-fat KP, Koeppe (margin) and Busacca (stromal) iris nodules, or cataract. Characterized by dense synechia with possible glaucoma from iris bombe´ pupillary block, PAS, or TM damage (11 to 23%). Intermediate uveitis with large epithelioid cells in the anterior vitreous, snowbanking and ‘‘snowballs’’ usually 360 degrees, unlike pars planitis. Posterior uveitis is less frequent but has perivenous sheathing (‘‘candle-wax drippings’’), retinitis, CME, retinal NV, choroiditis, and granulomas of the choroid or ON.

Primarily affects Caucasians worldwide, but more prevalent in African-American patients in the United States. F > M; 20 to 50 years old. Younger patients usually have acute unilateral disease versus older patients with bilateral chronic disease. Rare in children who may only have rash, arthritis, and uveitis.

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

Work-up: consider serum ACE, lysozyme, CXR, skin testing, gallium scan, tissue biopsy if lacrimal involved or granuloma of the skin or conjunctiva, or broncho-alveolar lavage.

Treat with prednisone 80–100 mg qd and PF 1% every 1 hour; taper oral dose with response to 10–20 mg over 3 to 4 weeks. Cyclosporine for steroid-sparing agent.

SYMPATHETIC OPHTHALMIA (SO) Rare but classic chronic, bilateral, granulomatous panuveitis from immune reaction to the injured (exciting) eye, causing the fellow (sympathizing) eye to also become inflamed anywhere from 10 days to 50 years later. Estimated incidence of 0.2% of eyes postinjury, 0.007 to 0.7% postcataract extraction, 1.4% of uveitis. Sixty-five percent occur within 2 weeks to 2 months, 80% occur within 3 months, and 90% within 1 year.

Hippocrates noted injury in one eye led to disease in fellow eye. Mackenzie (1840) described first case series. Fuchs (1905) elucidated etiology. Highest incidence reported during U.S. Civil War in 1860s, then few cases in World War I and II; none in Korean or Vietnam wars.

Immune reaction against self-antigen (possible retinal S or uveal antigen). Peripheral lymphocytes reacting against melanin may account for the vitiligo and poliosis that are often seen. Anterior chamber associated immune deviation (ACAID) causes AC antigen suppression. There is a reported decreased SO incidence after glaucoma filtering surgery. Associated with HLA-A11.

Presents with insidious pain and photophobia in both eyes, with decreased VA and early loss of accommodation from cyclitis. Granulomatous iridocyclitis with large mutton-fat KP, extensive PAS, nodular thickened iris, and choroid. Dalen-Fuchs nodules are creamcolored choroidal lesions that are sub-RPE excrescences of Bruch’s membrane composed of T cells, 60–700 mm, in the midperiphery. The choroiditis spares the choriocapillaris and the retina (unlike VKH); thus, not likely to have serous RD. Patients may also have cataract, rubeosis, glaucoma, and papillitis. May look like VKH, with poliosis, vitiligo, and meningeal signs, but with an ocular trauma history. FA shows irregular choroidal filling, multiple leakage, and early hypoand later hyperfluorescence.

Differential diagnosis: VKH, phacoantigenic (SO has up to a 25% coincidence with lens-induced uveitis from traumatic etiology), syphilis, and sarcoidosis

Treatable with lifelong immunosuppression with steroids and cyclosporin. Sixty-five percent of patients retain 20/60 vision or better. Prevent SO following trauma by enucleating a blind, painful eye within 2 weeks.

SYPHILIS Sexually transmitted chronic, systemic infection caused by the spirochete Treponema pallidum, and is the cause of 1 to 3% of all uveitis.

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

198 UVEAL TRACT AND OCULAR INFLAMMATION

Is a uveitis that can be cured, it is considered the ‘‘great masquerader.’’ May be acquired or congenital if mother was in primary or secondary stage of infection. Risk increased in AIDS patients.

Screen patients with treponemal tests FTA-Abs or MHA-TP. The nontreponemal tests, VDRL and RPR, detect antilipoidal Ab produced during active treponemal infection and may be normal after treatment or in tertiary disease; also may be falsely negative with RA, SLE. Ocular involvement implies neurosyphilis; thus, do lumbar puncture, and check CSF VDRL.

Four potential stages:

Primary: incubation period of 3 weeks, followed by skin or mucous membrane chancre from 8 days to 6 weeks after infection with regional lymphadenopathy. Painless chancre heals within a few weeks. If congenital, may cause bilateral acute interstital keratitis with stromal vessels and later ghost vessels, keratouveitis, retinitis with salt and pepper fundus, RPE degeneration, and optic atrophy (looks like RP).

Secondary: if untreated, the spirochetemic stage follows within a few weeks or months after disappearance of the primary chancre, with fever, malaise, headache, generalized lymph node enlargement, arthralgias, and rash. Also may have conjunctivitis, keratitis, uveitis (granulomatous or not, can look like anything) with iris nodules. Usually not posterior, but may have focal or multifocal choroiditis, exudates around disk and arterioles, arteritis, extensive RPE hypertrophy, and papillitis neuroretinitis. Secondary stage subsides, even without antibiotic therapy, and the infection becomes latent.

Latent: untreated patients with historic or serologic evidence for syphilis but with no clinical manifestations have latent syphilis. Secondary syphilitic relapses may develop during this state of latency. Most patients stay latent.

Tertiary (neurosyphilis): 30% of untreated cases will progress to the tertiary stage, with syphilitic inflammatory lesions of the heart, aorta, brain, kidney, bone, eye, or skin. Ocular findings include Argyll-Robertson pupils with blurred vision, chorioretinitis (bilateral in 50%), vitreous haze, flame hemorrhages, chorioretinal atrophy, periarterial sheathing, diffuse neuroretinitis, IK, and punctate keratitis.

Treat with IV penicillin 12–24 million units/day for 10 days, then Benzathine penicillin G 2.4 million units IM for 3 weeks plus topical steroids for ocular inflammation. Watch for Jarisch-Herxheimer reaction (increased inflammation and exudate with treatment from death of treponemes). Check CSF every 6 months until cells, protein, and VDRL normalize.

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.

TUBERCULOSIS Aerobic bacillus with predilection for highly oxygenated tissues (lung apex and choroid) that may cause uveitis from direct infection or hypersensitivity reaction (type IV). At-risk populations: health care workers, endemic areas, indigent or immunocompromised patients. May present as a granulomatous iridocyclitis, vitritis, choroiditis with yellowwhite choroidal nodules, retinal periphlebitis, vascular occlusions, or papillitis. Check PPD (confounded by bacille Calmette-Gue´rin [BCG] vaccine and atypical Mycobacterium infections), CXR, and possibly aqueous PCR. May give a Schlaegel trial: isoniazid (INH) for 2 weeks. Treat active tuberculosis with INH, rifampin, and pyrazinamide.

VOGT-KOYANAGI-HARADA DISEASE (VKH), UVEOMENINGEOENCEPHALITIS

Cause of 18% of panuveitis, usually with severe bilateral granulomatous inflammation with bilateral serous RD, iridocyclitis, choroidal thickening, disk edema, meningeal irritation, poliosis, and vitiligo. Vogt described the first case (1906), Harada added retinal findings (1926), and Koyanagi described neurologic characteristics (1929).

Almost always presents in pigmented races, especially Asian and Native American. Sixty percent of patients are female, usually 20 to 50 years old. Rarely affects children or Caucasians. Higher incidence in Japan than in Japanese immigrants in the United States. Etiology is likely from sensitivity to melanin, as evidenced by vitiligo, poliosis, iris depigmentation with recurrent anterior attacks, ‘‘sunset glow’’ fundus with chronic posterior inflammation as the body depigments, highfrequency hearing loss (cochlea contains melanin), and neurologic symptoms (melanin in the CNS meninges). Asians have more recurrent anterior uveitis than Westerners, who have more posterior signs and symptoms.

Diagnosis: clinical findings, may have positive HLA-DR4, Dw53 in 75% of cases. Ultrasound shows diffuse low choroidal reflectivity (usually increased with posterior scleritis).

Three stages:

Prodromal stage: few days of headache, nausea, tinnitis, dysacusis or hearing loss, and orbital pain.

Uveitic or ophthalmic stage: rapid onset with bilateral posterior uveitis, choroidal fullness, retinal edema, papillitis, multifocal choroidal inflammation, and SRF accumulation with serous RD; may have ACG from annular choroidal effusion.

Convalescent stage: Dalen-Fuchs nodules are present with chorioretinal scarring. Sugiura sign is pathognomonic with perilimbal vitiligo from loss of basal melanosomes.

Differential diagnosis: syphilis (may also have bilateral serous RD) and birdshot retinochoroidopathy (may have retinal lesions associated with vitiligo)

Goodman, Ophtho Notes © 2003 Thieme

All rights reserved. Usage subject to terms and conditions of license.