Dose-Response Relationship between Intravitreal Injections and Retinal Nerve Fiber Layer Thinning in Age-Related Macular Degeneration

Purpose: To determine if multiple intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors for unilateral exudative age-related macular degeneration (eAMD) are associated with thinning of the retinal nerve fiber layer (RNFL), we compared RNFL thickness measurements from the injected eye with that of the fellow eye with nonexudative age-related macular degeneration (neAMD). Design: Retrospective, cross-sectional study. Participants: Patients undergoing anti-VEGF therapy for unilateral eAMD. Methods: Patients receiving anti-VEGF therapy secondary to eAMD in 1 eye with neAMD in their fellow eye were identified. Patients with a known diagnosis of glaucoma were excluded. Spectral domain OCT measurements of the peripapillary RNFL thickness from both eyes were performed and compared. The differences in the RNFL thickness measurements between eyes were correlated with the number of injections and the duration of therapy. Main Outcome Measures: Correlation between the number of anti-VEGF injections and peripapillary RNFL thinning. Results: A total of 108 eyes of 54 patients were evaluated in this study. The average peripapillary RNFL thickness measurements of the injected eye and fellow eye were 87.3 ± 9.6 μm and 89.0 ± 7.5 μm, respectively (P = 0.055). The RNFL thickness difference (fellow eye minus injected eye) was significantly correlated with the number of injections (r = 0.40, P = 0.002) and months of injections (r = 0.38, P = 0.005). The relationship between the difference in the RNFL thickness and the number of injections had a nonlinear dose-response relationship that became apparent after approximately 30 injections and 50 months of injections. Conclusions: The difference in RNFL thickness measurements between injected eyes and uninjected fellow eyes was largely within the reported normal limits for interocular differences between healthy eyes. Nevertheless, there was a dose-response relationship between RNFL thinning and number of injections among patients receiving a greater number of injections, suggesting that anti-VEGF injections may have a modest effect on the RNFL thickness after several years of therapy in eyes requiring more anti-VEGF injections; however, we cannot exclude that the RNFL thinning may be secondary to active age-related macular degeneration (AMD) disease progression in both eyes.