What is the treatment approach for the spectrum of multifocal choroiditis, panuveitis, and subretinal fibrosis?

Treatment Approach for Multifocal Choroiditis, Panuveitis, and Subretinal Fibrosis Spectrum

Systemic immunosuppressive therapy is the definitive treatment for multifocal choroiditis with panuveitis (MCP) and should be initiated early to prevent vision-threatening complications, particularly choroidal neovascularization and subretinal fibrosis. 1, 2

Disease Spectrum and Clinical Recognition

This spectrum represents a progressive inflammatory chorioretinal disorder characterized by:

• Multifocal choroiditis with panuveitis (MCP): Multiple yellow-white or gray focal lesions at the level of the retinal pigment epithelium and choroid, accompanied by inflammation in all uveal compartments (anterior, intermediate, and posterior) 3, 4
• Subretinal fibrosis: Progressive scarring that develops as a late-stage complication, causing permanent vision loss when involving the macula 5, 6
• Associated complications: Choroidal neovascularization (22% at presentation), cystoid macular edema, epiretinal membrane formation, cataract, and glaucoma 2, 4

The disease predominantly affects young to middle-aged adults, shows female predominance, and typically presents bilaterally, though rare unilateral cases exist 3, 6

Diagnostic Workup Requirements

Multimodal imaging is essential to establish diagnosis and guide treatment:

• OCT: Identifies subretinal fluid, outer retinal disruption, cystoid macular edema, and subretinal fibrosis 3
• Fluorescein angiography (FA): Demonstrates focal leakage points and choroidal neovascularization 3, 2
• Indocyanine green angiography (ICGA): Shows hypofluorescent changes on late-phase imaging characteristic of white dot syndromes 3
• OCT-angiography: Detects neovascular networks when present 3

Rule out infectious and systemic causes before initiating immunosuppression, including tuberculosis, bartonellosis, Lyme disease, sarcoidosis, and inflammatory bowel disease 5, 7

Treatment Algorithm

Initial Management

Corticosteroids alone are insufficient and associated with significant complications including cataract, glaucoma, and systemic adverse effects in the majority of patients 1, 4

• Local corticosteroids (topical drops, periocular injections) may be used for acute inflammation control 3, 4
• Systemic corticosteroids should only be used in combination with immunosuppressive agents, never as monotherapy 7

Definitive Immunosuppressive Therapy

Systemic immunomodulatory therapy is the cornerstone of treatment and should be initiated promptly:

• First-line agents: Methotrexate (7.5 mg/week) or mycophenolate mofetil 5, 6
• Alternative agents: Azathioprine, cyclosporine-A, or other non-biologic immunosuppressants 1, 7
• TNF inhibitors: Adalimumab is FDA-approved for non-infectious panuveitis in adults and children ≥2 years and represents an effective option for refractory cases 8, 7

Evidence supporting immunosuppressive therapy:

• 83% reduction in risk of posterior pole complications 2
• 92% reduction in risk of vision loss to 20/200 or worse 2
• No patient lost vision once immunomodulatory therapy was instituted in one series 1
• Controls inflammation and prevents progression to subretinal fibrosis 1, 5

Management of Choroidal Neovascularization

When choroidal neovascularization develops (the leading cause of vision loss in this spectrum):

• Intravitreal anti-VEGF injections are the primary treatment 3, 2
• Continue systemic immunosuppression concurrently, as it reduces recurrence risk by 92% (only 1 of 6 eyes with CNV recurred on immunosuppressive therapy) 2
• Photodynamic therapy may be considered as adjunctive treatment in select cases 3

Long-term Monitoring Strategy

Regular ophthalmologic surveillance is mandatory:

• Monitor for at least 3 years after achieving remission to detect recurrence early 7
• Assess for development of choroidal neovascularization (incidence rate 0.13/eye-year in affected eyes) 2
• Screen for steroid-induced complications (cataract, glaucoma) 1, 4
• Monitor for systemic immunosuppression-related adverse effects 1

Critical Pitfalls to Avoid

Delaying immunosuppressive therapy leads to irreversible complications:

• Patients treated with steroids alone developed serious complications and vision loss 1
• Two patients who refused immunomodulatory therapy lost considerable vision in 3 of 4 eyes 1
• Subretinal fibrosis, once established, causes permanent vision loss (e.g., 90% loss of visual efficiency in one case despite treatment) 5

Failing to screen for infections before starting immunosuppression can worsen occult infections and lead to poor outcomes 7

Treating choroidal neovascularization without systemic immunosuppression results in high recurrence rates 2

Underestimating disease severity: 55% of affected eyes have vision 20/50 or worse at presentation, and 38% have vision 20/200 or worse, emphasizing the need for aggressive early intervention 2