Clinical Efficacy of Switching to Faricimab in Treatment Resistant Neovascular Age-Related Macular Degeneration: Systematic Review and Meta-analysis

Am J Ophthalmol. 2025 Dec:280:248-266. doi: 10.1016/j.ajo.2025.08.034.

Summary

Systematic review and meta-analysis: Treatment resistant nAMD Switch to Vabysmo improves retinal thickness without VA change. Greater effect with a loading interval protocol.

Abstract

Topic: Faricimab in the treatment of treatment-resistant neovascular age-related macular degeneration (nAMD).

Clinical relevance: While many studies on faricimab in treatment-resistant eyes have reported improvements in retinal thickness (RT), the impact on visual acuity (VA) remains inconsistent. Additionally, variability in dosing protocols-with some studies utilizing loading interval for the first 3 injections while others continuing at the prior injection interval-introduces further uncertainty regarding the optimal treatment strategy. Understanding these differences is essential for guiding clinical decision-making and maximizing patient outcomes.

Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251000088). A systematic search of PubMed, Embase, and Scopus (February 3, 2025) identified studies evaluating the effects of switching to faricimab in treatment-resistant nAMD. Inclusion criteria required patients to have received ≥3 prior anti-VEGF injections and ≥3 faricimab injections, with reported outcomes on RT, VA, fluid status, or injection intervals. Outcomes were measured following completion of loading dose and at last follow up, ranging from 3 months to 1.5 years. Studies were assessed for bias using ROBINS-I and NIH Quality Assessment tool and assessed for certainty of evidence using GRADE. Meta-analyses were conducted using mean differences, odds ratio, and random-effects models.

Results: Fourteen studies (926 eyes) met inclusion criteria. Switching to faricimab significantly reduced RT by 46.67 µm (95% CI: 35.91-57.42, I2 = 0%, 721 eyes). Eyes that followed a loading interval were found to have greater reduction in RT than those that did not (I2 = 74.1%, 640 eyes). The odds of achieving a dry macula increased 4.35-fold (95% CI: 2.95-6.42, I2 = 64%, 379 eyes). Eyes with baseline VA <65 ETDRS letters showed a gain of 3.16 letters (95% CI: 0.80-5.52, I2 = 0%, 439 eyes). Injection intervals were extended by 1.56 weeks (95% CI: 0.71-2.40, I2 = 86%, 591 eyes). Using GRADE, 4 outcomes were graded as either very low (VA, dryness, and treatment interval) or low (RT).

Conclusion: Switching to faricimab in treatment-resistant nAMD eyes significantly improved RT with no change in VA. This effect was greater with a loading interval protocol. Overall, there was an extension of injection intervals. Further prospective studies are needed to optimize dosing strategies and assess long-term efficacy.