Vogt-Koyanagi-Harada Disease

Vogt-Koyanagi-Harada (VKH) disease is a bilateral granulomatous panuveitis with exudative retinal detachments and neurological, auditory and cutaneous manifestations, mediated by a T-cell autoimmune response against melanocyte antigens (tyrosinase family proteins).

• More common in pigmented races: Asians, Hispanics, Middle Eastern, Native American and African populations; age 20 to 50 years; women more than men (about 2:1).
• Associated with HLA-DRB1*0405 and HLA-DR4. Triggers include viral infection, and sometimes prior skin injury.
• Disease phases: prodromal, acute uveitic, convalescent, and chronic recurrent.

• Prodromal (days to 2 weeks): headache, nausea, fever, neck stiffness, meningism, tinnitus, vertigo, hearing loss (dysacusis), scalp hypersensitivity and pain, photophobia.
• Acute uveitic phase (weeks): bilateral blurred vision, diffuse choroiditis with multifocal subretinal fluid, serous exudative retinal detachments (especially inferior), disc hyperaemia and oedema, thickened choroid, mild to moderate anterior chamber reaction with granulomatous keratic precipitates, vitritis, raised pressure from angle closure caused by ciliary body oedema.
• Convalescent phase (months): depigmentation of the choroid (sunset glow fundus), Dalen-Fuchs nodules, Sugiura sign (perilimbal vitiligo), poliosis (white eyelashes and hair), vitiligo, alopecia.
• Chronic recurrent phase: recurrent granulomatous anterior uveitis, cataract, glaucoma, choroidal neovascularisation, subretinal fibrosis.

• Clinical diagnosis, based on bilateral involvement without history of trauma or surgery, with compatible ocular, neurological, auditory and skin findings.
• Fluorescein angiography: multiple pinpoint areas of early leakage at the level of the retinal pigment epithelium with later pooling in serous detachments, and disc staining.
• Enhanced depth imaging optical coherence tomography: thickened choroid, subretinal fluid with septa; B-scan: diffuse choroidal thickening; indocyanine green angiography: hypofluorescent dark dots.
• Lumbar puncture: lymphocytic pleocytosis (in about 80 percent in the first 3 weeks), audiometry, and exclusion of other causes (syphilis, tuberculosis, sarcoidosis, lymphoma, sympathetic ophthalmia).

• Early, adequate, aggressive treatment improves outcome and reduces chronic disease and sunset glow fundus.
• Initial therapy: intravenous methylprednisolone 1 g daily for 3 days (or 500 mg for milder presentations), followed by oral prednisolone 1 mg/kg daily (60 to 80 mg) tapered slowly over at least 6 months (by 5 to 10 mg every 2 weeks initially; relapses are common if tapered within 3 months).
• Topical prednisolone acetate 1 percent four times daily and cycloplegic (atropine 1 percent daily, cyclopentolate 1 percent) for anterior inflammation; pressure control.
• Steroid sparing agents early (especially in recurrent or chronic disease, or to shorten steroid exposure): ciclosporin 3 to 5 mg/kg daily, mycophenolate mofetil 1 g twice daily, azathioprine 2 mg/kg daily, methotrexate 15 to 25 mg weekly, and adalimumab 80 mg then 40 mg every 2 weeks or infliximab 5 mg/kg for refractory disease.
• Complications: cataract surgery after at least 3 months of quiet inflammation with perioperative steroid cover; glaucoma (aqueous suppressants, laser iridotomy for angle closure, filtering surgery); choroidal neovascularisation (intravitreal bevacizumab 1.25 mg or aflibercept 2 mg); subretinal fibrosis.
• Monitor visual acuity, anterior chamber activity, OCT choroidal thickness, and extraocular signs; screen for steroid effects (bone density, glucose, blood pressure).