Clinical trials and quasi-experimental studies in the treatment of noninfectious retinal vasculitis: A systematic review from the International Uveitis Study Group (IUSG) Retinal Vasculitis Study (ReViSe) - Report 4.

This systematic review evaluates clinical trials and quasi-experimental studies reporting diagnostic criteria, disease activity scoring systems (including Disease Activity Index (DAI), Total Inflammatory Activity Index (TIAI), and Total Adjusted Disease Activity Index (TADAI), and others), and therapeutic strategies used in noninfectious retinal vasculitis (RV), aiming to consolidate current evidence on treatment response and effectiveness measures. Of 5533 articles screened (PROSPERO: CRD42023489232), 15 studies met the inclusion criteria. Most were conducted in Asia (73.3 %) and focused on Behçet disease (60 %) or Eales disease (27 %). RV was diagnosed clinically in all studies, while half incorporated fluorescein angiography to confirm vascular inflammation through leakage, staining, or occlusion; however, definitions of RV were highly variable, often inferred rather than explicitly stated, and lacked standardization. This diagnostic inconsistency, combined with limited imaging data, undermines comparability across studies. Disease activity was assessed using outdated composite indices such as the DAI, TIAI, and TADAI, which lack external validation and fail to capture key clinical features such as macular ischemia or capillary non-perfusion. Best corrected visual acuity, although frequently reported, was confounded by unrelated factors such as cataracts or macular scarring. Therapeutic strategies included systemic corticosteroids, immunosuppressants (e.g., methotrexate, azathioprine), and biologics (e.g., infliximab, interferon-alpha). Treatment selection was heterogeneous, and several regimens-such as cyclophosphamide-azathioprine combinations-do not align with current standards of care. Due to variability in study design and outcome reporting, no pooled effect estimates, or statistical comparisons were conducted. Treatment outcomes were synthesized descriptively based on individual study findings. Current evidence in RV clinical trials is outdated and lacks diagnostic and therapeutic standardization. There is a particular need for RV-specific definitions, validated disease activity and response indices, and contemporary therapeutic trials to guide clinical management and improve outcome comparability.