Cochrane Review Protocol Targets Surgery vs Drugs for Sight-Threatening Uveitis

Non-infectious uveitis — particularly its intermediate, posterior, and panuveitic forms — represents a major cause of preventable blindness worldwide, disproportionately affecting working-age adults. Standard management relies on corticosteroids and immunomodulatory therapy (IMT), but these carry substantial long-term risks including cataract, glaucoma, infection, hepatotoxicity, and nephrotoxicity. The cumulative treatment burden is high, requiring frequent specialist visits and monitoring, and costs to individuals and healthcare systems are considerable. Despite these limitations, no rigorous systematic review has evaluated whether surgical intervention can meaningfully reduce this burden.

Pars plana vitrectomy (PPV) is a microsurgical procedure in which the vitreous gel is removed and replaced with balanced salt solution or a tamponade agent. In uveitis, its therapeutic rationale is compelling: PPV mechanically removes inflammatory cells, pro-inflammatory cytokines, and antigen-presenting hyalocytes from the vitreous cavity, potentially reducing the inflammatory load driving chronic disease. It may also improve penetration of topical and systemic drugs into the posterior segment and modulate the intraocular immune environment. Retrospective multicentre data on intermediate uveitis have suggested PPV is associated with higher rates of remission, hinting at a disease-modifying role beyond simple mechanical debulking.

This published Cochrane protocol establishes the methodology for a full systematic review comparing PPV (with or without adjunctive medical therapy) versus medical therapy alone. Eligible studies will be parallel-group RCTs with no restrictions on language, publication status, or year. Participants must have non-infectious intermediate uveitis, posterior uveitis, or panuveitis complicated by persistent inflammation or cystoid macular oedema (CMO). Studies including mixed infectious/non-infectious populations will be included only if ≥80% of participants meet non-infectious criteria or if subgroup data can be extracted separately.

The two critical outcomes are change in best-corrected visual acuity (BCVA) — measured by logMAR, Snellen, or ETDRS — and resolution or improvement of CMO assessed by OCT or fluorescein angiography. Important secondary outcomes include changes in intraocular inflammation graded by SUN criteria, corticosteroid and IMT dose changes, need for additional or repeat treatments, surgical adverse events (retinal detachment, intraocular pressure elevation, cataract progression), and health-related quality of life. Electronic searches will cover MEDLINE, Embase, CENTRAL, and Web of Science from inception, supplemented by ClinicalTrials.gov, WHO ICTRP, conference abstracts from ARVO, AAO, and EURETINA, and reference list and forward citation searches.

Two independent reviewers will screen records, extract data, and assess risk of bias using the Cochrane RoB 2 tool. Disagreements will be resolved by a third reviewer. Where sufficient homogeneous data exist, random-effects meta-analysis will be performed; heterogeneity will be explored through subgroup and sensitivity analyses. The GRADE framework will be used to evaluate certainty of evidence. This protocol is critically important because it will, for the first time, synthesize randomized evidence on whether surgery can replace or meaningfully reduce reliance on long-term immunosuppression in a disease with serious systemic drug toxicity risks — a question of direct relevance to both patients and clinicians.