Effect of Repeated Intravitreal Ranibizumab and Aflibercept Injections on the Cornea in Patients with Age-Related Macular Degeneration

Abstract

Purpose. To assess the effect of repeated intravitreal ranibizumab injections (RI) and aflibercept injections (AI) on the corneal endothelium and central corneal thickness (CCT) in patients with age-related macular degeneration (AMD). Materials and Methods. In the retrospective study, 110 eyes of 106 patients, aged 52 to 93 years, were analyzed. Fifty eyes were treated only with RI (I group), and 60 eyes were treated only with AI (II group). Every patient received one intravitreal injection of 0.5 mg of ranibizumab once a month or 2 mg of aflibercept for 3 subsequent months. Each patient received only 3 injections during the whole observation period. Corneal analysis was obtained with the specular microscope. Examinations were performed before initial treatment, after each injection, and 6 months after the first injection. Analysis included corneal endothelial cell density (ECD), hexagonal cell percentage (% Hex), coefficient of variation (CoV), and CCT. Results. There was a statistically significant ECD loss, regardless of the type of the anti-VEGF agent. The mean ECD value in the I group was 2397 ± 459 cells/mm2 before RI, 2389 ± 459 cells/mm2 after the first RI, 2386 ± 467 cells/mm2 after the second RI, 2378 ± 475 cells/mm2 after the third RI, and 2357 ± 460 cells/mm2 6 months after the first RI. The mean ECD value in the II group was 2448 ± 493 cells/mm2 before treatment, 2456 ± 498 cells/mm2 after the first AI, 2426 ± 496 cells/mm2 after the second AI, 2402 ± 488 cells/mm2 after the third AI, and 2348 ± 473 cells/mm2 6 months after the first AI. In comparison with the group treated with RI, the group treated with AI presented a greater ECD loss at each measuring point. The percentage of hexagonal cells was decreased in both groups. There was a slight increase in polymegathism in both treated groups. Ranibizumab proved to cause a small increase in CCT, while CCT remained unchanged in the aflibercept group. Conclusions. Repeated intravitreal injections of 0.5 mg of ranibizumab or 2 mg of aflibercept can influence the morphology of the corneal endothelium but not CCT.

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis

“…However, additional clinical data is still needed to study the long-term risk because anti-VEGF agents are in direct contact with the corneal endothelium. 84 …”

“…However, additional clinical data is still needed to study the long-term risk because anti-VEGF agents are in direct contact with the corneal endothelium. 84 Studies have found that LMSCs have the potential to treat corneal injuries, and repeated intravitreal injection of anti-VEGF drugs may reduce LMSC reserves due to their toxic effects. There is a case report of a patient who developed iatrogenic limbal stem cell deficiency due to the intravitreal injection of bevacizumab seven times, indicating that repeated surgical trauma to the limbus and surrounding areas may damage the LMSCs.…”

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs

“…For instance, Merz et al [6] found that Ranibizumab and Bevacizumab were not toxic to corneal endothelial cells under in vitro experimental conditions. However, Beata et al [7] performed a retrospective study on patients with nAMD and discovered that Aflibercept and Ranibizumab could significantly reduce the corneal endothelial cell density (ECD), additionally, the proportion of hexagonal cells (Hex%) and CV also changed to a certain extent. Most of the above reports are retrospective in nature, and most of the literature reports are observations made following the administration of a particular drug for a specific disease.…”