Mode
Text Size
Log in / Sign up

Subretinal fibrosis develops in 40-50% of nAMD eyes after 5 years of anti-VEGF therapy, associated with worse visionHow often does scarring develop in treated macular degeneration eyes?

AI-generated summary of the cited source, checked by automated accuracy review. How we work

Key Takeaway
Note that fibrosis develops in many nAMD eyes on long-term anti-VEGF and associates with worse vision.

This systematic review and meta-analysis examined imaging-defined fibrosis in neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy. The analysis included 58 studies (12 randomized trial secondary analyses, 18 prospective studies, 28 retrospective studies) involving eyes with nAMD receiving intravitreal anti-VEGF therapy, comparing different dosing regimens (fixed or treat-and-extend vs pro re nata).

The review found subretinal fibrosis developed in approximately 10-15% of eyes within 2 years of anti-VEGF therapy and 40-50% by 5 years. Eyes with fibrosis had consistently worse visual outcomes, with a pooled best-corrected visual acuity difference of -29 ETDRS letters (95% CI -47 to -12). Type 2 macular neovascularisation (OR 5.7), subretinal hyperreflective material (OR 2.7), intraretinal fluid (OR 3.6), and large haemorrhage (OR 2.3) were associated with higher odds of incident fibrosis, while subretinal fluid was associated with lower odds (OR 0.6).

Safety and tolerability data were not reported. A key limitation was substantial heterogeneity in imaging definitions and grading methods for fibrosis across studies, limiting cross-study comparability. The authors note that standardized OCT-anchored definitions, reproducible quantitative measures, and functional endpoints beyond BCVA are needed to advance anti-fibrotic therapeutic development and improve long-term visual outcomes. All findings represent associations, not causation.

For people receiving regular eye injections for neovascular macular degeneration, the growth of scar tissue in the retina remains a serious concern. A major review of 58 studies found that this scarring, called subretinal fibrosis, developed in roughly 10-15% of treated eyes within two years, and in 40-50% by five years. Eyes that developed this scarring had vision that was, on average, about 29 letters worse on a standard eye chart than eyes without it.

The research also looked at what might be linked to a higher risk of scarring. Eyes with certain features at the start of treatment—like a specific type of abnormal blood vessel growth or certain types of fluid or bleeding—had higher odds of developing fibrosis. Interestingly, a different type of fluid under the retina was linked to lower odds. The analysis also suggested that eyes on a more regular injection schedule (fixed or treat-and-extend) might have a lower incidence of scarring than those treated only as needed.

It's crucial to understand what this review can and cannot tell us. The findings show associations, not proof of cause and effect. A major limitation is that the studies used widely different methods to define and measure scarring on eye scans, making it hard to compare results precisely. This means the reported percentages should be seen as a range, not a precise prediction. The work clearly shows that scarring is a common and vision-harming complication, underscoring the need for better, standardized ways to define it in future research.

What this means for you:
Retinal scarring develops in many treated macular degeneration eyes and is linked to worse vision.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
BackgroundDespite intravitreal anti–vascular endothelial growth factor (VEGF) therapy being the standard of care for neovascular age-related macular degeneration (nAMD), long-term visual decline remains common, with subretinal fibrosis representing a major cause of irreversible vision loss. Objective: To systematically evaluate how imaging-defined fibrosis in nAMD is defined and quantified, its incidence under anti-VEGF therapy, associated baseline associations, and its impact on visual outcomes.MethodsWe systematically searched MEDLINE, Embase, CENTRAL, and Scopus through September 2025 for studies reporting imaging-defined fibrosis in anti-VEGF–treated nAMD. Eligible studies included randomized controlled trial secondary analyses, prospective and retrospective cohorts, and registries. Two reviewers independently extracted data on fibrosis definitions, imaging modalities, associations, and functional outcomes. Random-effects meta-analyses pooled the best-corrected visual acuity (BCVA) difference (ETDRS letters) and the odds ratio for incident fibrosis. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool, and the certainty of evidence was evaluated using the GRADE approach.ResultsFifty-eight studies were included (12 randomized trial secondary analyses, 18 prospective studies, and 28 retrospective studies). Across studies, subretinal fibrosis developed in approximately 10–15% of eyes within 2 years and 40–50% by 5 years of anti-VEGF therapy, with a lower incidence under fixed or treat-and-extend regimens compared with pro re nata dosing. Eyes with fibrosis had consistently worse visual outcomes (pooled BCVA difference −29 ETDRS letters; 95% CI −47 to −12). Key associations included type 2 macular neovascularisation (OR 5.7), subretinal hyperreflective material (OR 2.7), intraretinal fluid (OR 3.6), and large haemorrhage (OR 2.3), while subretinal fluid appeared protective (OR 0.6). Definitions and quantification approaches varied widely across imaging modalities.ConclusionsFibrosis remains a frequent and vision-limiting sequela of treated nAMD, with substantial heterogeneity in imaging definitions and grading methods limiting cross-study comparability. Standardised OCT-anchored definitions, reproducible quantitative measures, and functional endpoints beyond BCVA are needed to advance anti-fibrotic therapeutic development and improve long-term visual outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420231132016.
Free Newsletter

Clinical research that matters. Delivered to your inbox.

Join thousands of clinicians and researchers. No spam, unsubscribe anytime.