Effects on corneal endothelium of intravitreal injection of anti-VEGF drugs.

Purpose: Intravitreal drug administration has become the gold standard for the treatment of many retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinal vein occlusion (RVO). The frequency of this procedure has increased significantly after the introduction of anti-VEGF drugs, since the rise in the average age of the population, which is closely correlated with these diseases. In order to ensure therapeutic success in these patients with chronic retinal diseases, intravitreal treatment with anti-VEGF requires a long-term maintenance regimen with repeated administrations. For this reason today, we must consider the risks linked to complications associated with the long-term application of this therapy. Our study aims to investigate whether the intravitreal injection of anti-VEGF may lead to damage to the corneal endothelium, either directly through the administration procedure or indirectly due to the drug's toxicity. We aimed to establish a clear correlation between intravitreal drug administration and a statistically significant reduction in corneal endothelial cell count in the treated eye when compared to the untreated eye. The study also sought to assess whether different toxicities might be present between different types of drugs belonging to the same anti-VEGF family.

Materials and methods: The study was conducted by examining a cohort of 133 patients suffering from different diseases: AMD, EMD and RVO. All patients underwent measurement of the endothelial count with CellChek^® 20, considering the value measured at the first injection as time zero and reassessed at each subsequent treatment session. The measurement of the endothelial count was performed both on the eye under treatment (TE) and in the eye not undergoing intravitreal injection (NTE) with anti-VEGF drugs for each injection cycle. Different anti-VEGF drugs such as Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab were used for intravitreal therapy. The test patients were included in a 12-month follow-up programme, in which the measurement intervals are dictated by the treatment plan.

Results: The statistical analysis performed on the corneal endothelial cell counts showed that the ECD (endothelial cell density) parameter decreases with each administration of the drug. The analysis of the difference in the mean endothelial cell counts of the TE reveals that the difference in the number of endothelial cells between the first and second counts in TE is 54.00; greater than the difference in the number of cells found in NTE, which was 13.42. Both the difference between the TE and NTE cell counts are statistically significant. In the case of the TE, the p-value is <0.001, while in the case of the NTE the p-value is still significant as <0.05. The hypothesis that the different types of anti-VEGF drugs could determine the decrease in endothelial cell count differently was also evaluated. No statistically significant data emerged from the analyses (p-value is >0.05).

Conclusions: The study demonstrated a statistically significant reduction of corneal endothelial cells in patients undergoing intravitreal injection treatment per number of injections with anti-VEGF, this reduction being independent of the type of anti-VEGF used (Bevacizumab, Ranibizumab, Aflibercept and Brolucizumab).