Risk of Retinal Detachment After Intravitreal Injection of Anti-VEGF: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents.

Intravitreal anti-VEGF injections are the most frequently performed intraocular procedure, with RD remaining a poorly quantified complication. Pooled estimates equip clinicians to contextualize RD risk during informed consent.

This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD420251175527). MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 18, 2026. Included studies reported RD risk after anti-VEGF IVI for neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema from retinal vein occlusion, proliferative diabetic retinopathy, or myopic choroidal neovascularization. Paired reviewers independently extracted data and assessed risk of bias using ROBINS-I and the Joanna Briggs Institute checklist for case series. A random-effects single-arm meta-analysis of proportions using a generalized linear mixed model generated pooled risk estimates per injection and per eye.

Twelve studies comprising 834 814 injections and 119 RD events were included. In the meta-analysis of 9 studies (787 849 injections), there were 92 rhegmatogenous RD (RRD) events, with a pooled risk of 0.012% (95% CI [0.009-0.015%], I²: 14.4%), equivalent to 1 in 8675 injections. An acute ≤90-day postprocedural sensitivity analysis yielded a consistent RRD risk of 0.013% (95% CI [0.010-0.016%], I²: 36.8%) (approximately 1 in 7692 injections). An eye-level sensitivity analysis yielded a per-eye risk of 0.08% (95% CI [0.02-0.31%], I²: 66.7%) (approximately 1 in 1250 eyes). Exploratory subgroup analyses showed no differences in RRD risk by injection number (≥100 000 vs <100 000; P = .520), study setting (single-center vs multicenter; P = .258), injection indication (nAMD only vs mixed; P = .061), injection provider (ophthalmologist vs mixed; P = .259), or risk of bias (P = .356). One study evaluating severe PDR reported tractional RD risk as 3.6% (95% CI [2.3-5.2%]) (approximately 1 in 28 injections), likely reflecting disease-specific fibrovascular contraction.

Low-certainty evidence indicates RRD following anti-VEGF IVI is uncommon, with a per-injection risk of 0.012% (1 in 8675 injections). Per-eye risk was 0.08% (1 in 1250 eyes), which was subject to wider uncertainty but more relevant to patients undergoing long-term treatment; notably, the pooled mean of 13.8 injections per eye in the contributing studies likely underestimates real-world cumulative exposure. Future work should incorporate eye-level denominators and standardized reporting of RD subtypes, ocular characteristics, and injection technique to enable risk stratification and identification of modifiable procedural contributors.