Dose-Response Relationship Between Recurrent Intravitreal Injections and Retinal Nerve Fiber Layer Thinning in Exudative AMD.

Abstract 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 to that of the fellow eye with non-exudative AMD (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 one eye with neAMD in their fellow eye were identified. Patients with a known diagnosis of glaucoma were excluded. Spectral domain optical coherence tomography (SD-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 One hundred and eight 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 non-linear dose-response relationship that become apparent after approximately 30 injections and 50 months of injections. Conclusions The difference in RNFL thickness measurements between injected eyes and un-injected fellow eyes were 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 AMD disease progression in both eyes.