Effect of Anti-Vascular Endothelial Growth Factor Therapy on Corneal Nerves

Purpose: Vascular endothelial growth factor (VEGF) is a trophic factor for corneal nerves (CNs). Despite its widespread use to treat a variety of retinal diseases, the effect of repetitive intravitreal (IV) anti-VEGF injections on CN is not known. Methods: Retrospective case-control study. CN parameters were compared between eyes in 39 individuals who received anti-VEGF injections in one eye only. Next, we compared CN parameters between 50 eyes of 50 individuals with a history of IV anti-VEGF injections and 80 eyes of 80 individuals without a history of injection. In vivo confocal microscopic examination was conducted using the ConfoScan 4. Images were analyzed by the Corneal Nerve Analysis tool. Paired and independent t test methodologies were used to compare nerve parameters, and multivariable linear regression analysis was performed to control for potential confounders. Results: In 39 patients (own controls), eyes with a history of IV injection had lower CN length density, total length, nerve fibers, bifurcations, and branches (P, 0.005) compared to the fellow eyes without injection. Similar findings were seen in the eyes of 50 individuals with a history of injection compared to 80 individuals without injection. A history of IV injections and ethnicity remained significantly associated with the CN length density and explained 32% of the variability (R = 0.56). Conclusions: We found decreased CN parameters in eyes with a history of anti-VEGF injections compared to eyes without such a history.