What is the recommended treatment for Vogt‑Koyanagi‑Harada disease presenting with bilateral granulomatous panuveitis?

Treatment of Vogt-Koyanagi-Harada Disease

The optimal first-line treatment for acute VKH disease presenting with bilateral granulomatous panuveitis is high-dose systemic corticosteroids combined with mycophenolate mofetil (MMF) initiated simultaneously from disease onset. 1

Evidence for Combination Therapy from Onset

The superiority of early combination therapy over corticosteroids alone is striking:

• Visual acuity of 20/20 was achieved in 93.4% of eyes when MMF was combined with high-dose corticosteroids from the outset, compared to only 38% with corticosteroids alone. 1
• No eye progressed to chronic recurrent granulomatous uveitis when MMF was used from disease onset, whereas progression occurred frequently with corticosteroid monotherapy. 1
• Recurrence of inflammation ≥3 times was reduced from 18% (corticosteroids alone) to 3% (corticosteroids plus MMF). 1
• Early aggressive treatment prevents the development of "sunset glow fundus," a hallmark of chronic disease that indicates irreversible choroidal depigmentation. 1, 2

Corticosteroid Dosing Protocol

• Initiate high-dose systemic corticosteroids (prednisone 1–1.5 mg/kg/day orally or equivalent intravenous methylprednisolone) immediately upon diagnosis. 3, 4
• Continue high-dose corticosteroids for at least 2–4 weeks before beginning a slow taper over several months. 5, 2
• Premature or rapid corticosteroid tapering is a critical pitfall that leads to chronic recurrent inflammation, cataracts (25% of patients), glaucoma (33%), and subretinal neovascular membranes (10%). 5

Immunomodulatory Therapy Selection

First-Line: Mycophenolate Mofetil

• Mycophenolate mofetil should be started simultaneously with corticosteroids at disease onset, not reserved for steroid-refractory cases. 1
• MMF demonstrates superior outcomes in preventing chronic recurrent disease compared to delayed initiation. 1

Alternative First-Line: Methotrexate

• Methotrexate has comparable efficacy to MMF for inflammation control and steroid-sparing effect, with no evidence of superiority of one over the other (grade C recommendation). 6, 1
• Either MMF or methotrexate is acceptable as first-line immunomodulatory therapy when combined with corticosteroids. 6

Second-Line: Azathioprine

• Azathioprine demonstrated inflammation control in 85.5% of acute VKH cases and 90% of chronic cases, with a median time to steroid-sparing effect of 4 months. 6, 1
• However, azathioprine is based on lower-level evidence (EL 4) from small cohorts and should be reserved for patients who cannot tolerate MMF or methotrexate. 6
• Approximately 17–24% of patients discontinue azathioprine within the first year due to ineffectiveness or adverse events. 6

Second-Line: Calcineurin Inhibitors

• Tacrolimus or cyclosporine are supported by grade B recommendation for VKH disease when first-line agents fail or are contraindicated. 6, 1
• Tacrolimus may be better tolerated than cyclosporine (6% vs 37% adverse events). 6, 1
• Cyclosporine was historically used but has been largely supplanted by MMF due to superior tolerability. 3, 5

Biologic Therapy for Refractory Disease

• Adalimumab (grade A recommendation) or infliximab (grade B/C recommendation) should be added when inflammation persists despite adequate corticosteroid and conventional immunosuppressive therapy. 6, 3
• TNF-α inhibitors are particularly indicated when hypotony, persistent optic disc edema, or declining visual acuity occurs despite conventional therapy. 3

Adjunctive Ocular Management

• Topical corticosteroids should be used for anterior uveitis and episcleritis as adjunctive therapy, not as monotherapy. 1
• Intravitreal anti-VEGF therapy is indicated if choroidal neovascularization develops during the disease course. 1
• Monitor intraocular pressure at every visit when using topical corticosteroids to detect steroid-induced glaucoma early. 1

Critical Monitoring Requirements

• Regular ophthalmologic examinations are essential to detect early disease progression, including visual acuity, slit-lamp findings, and fundoscopic changes. 1
• Optical coherence tomography (OCT) should be performed to monitor for exudative retinal detachments in acute disease and choroidal thinning in chronic disease. 4, 2
• Screen for systemic adverse effects of immunosuppressive therapy with specialist oversight, including complete blood counts and liver function tests. 1

Common Pitfalls to Avoid

• Never use corticosteroids as monotherapy beyond the initial weeks—this is the single most important error leading to chronic recurrent disease. 1, 5
• Do not delay initiation of immunomodulatory therapy until corticosteroid tapering fails; start MMF or methotrexate simultaneously with corticosteroids. 1
• Avoid rapid corticosteroid tapering; the taper should extend over several months to prevent rebound inflammation. 5, 2
• Do not undertreat based on unilateral presentation—95% of VKH cases are bilateral, and the second eye typically becomes involved within days to weeks. 1