Short-Term Corneal Endothelial Safety Of Anti-Vegf Treatment Regimens In Neovascular Age-Related Macular Degeneration: A Prospective Randomized Comparative Study

Short-term Corneal Endothelial Safety of Anti-VEGF Treatment Regimens in Neovascular Age-Related Macular Degeneration: A Prospective Randomized Comparative Study.compare the effects of continuous intravitreal bevacizumab monotherapy versus sequential bevacizumab-aflibercept treatment on corneal endothelial parameters in treatment-naïve patients with nAMD, with specific attention to potential differential effects on endothelial cell density, morphology, and corneal thickness over a 6-month treatment period.

 This prospective, randomized, parallel-group comparative study enrolled 70 treatment-naïve nAMD patients (one eye per patient) between December 2024 and May 2025. 

. Patients were randomized 1:1 to two treatment arms: Group 1 (n=35) received monthly intravitreal bevacizumab 1.25 mg for 6 consecutive months, while Group 2 (n=35) received monthly bevacizumab 1.25 mg for the initial 3 months followed by monthly aflibercept 2.0 mg for the subsequent 3 months. Non-contact specular microscopy (Tomey EM-4000) was performed by a single masked examiner to assess ECD ,HEX%,  CV,  CCT at baseline, 3 months, and 6 months. 

Seventy eyes from 70 patients (mean age 74.) completed the 6-month follow-up .  Baseline characteristics were balanced between groups with no significant differences in age, gender distribution, lens status, or baseline corneal parameters. Neither treatment regimen produced significant changes in any corneal endothelial parameter over the 6-month period. Group 1 (continuous bevacizumab), ECD changed from 2564±128 cells/mm² at baseline to 2561±130 cells/mm² at 3 months and 2549±131 cells/mm² at 6 months (p=0.31 for baseline vs. 6 months). In Group 2 (sequential therapy), ECD changed from 2559±125 cells/mm² at baseline to 2557±127 cells/mm² at 3 months and 2552±129 cells/mm² at 6 months (p=0.59). Between-group comparison at 6 months showed no significant difference (p=0.42, r=0.09). Hexagonality remained stable in Group 1 (baseline: 58.3±6.2%, 6 months: 57.9±6.4%, p=0.54) and Group 2 (baseline: 57.8±6.1%, 6 months: 57.5±6.3%, p=0.67), with no between-group difference (p=0.68, r=0.05). Coefficient of variation showed similar stability in both groups (Group 1: 31.2±4.1% to 31.5±4.3%, p=0.48; Group 2: 31.4±4.2% to 31.7±4.4%, p=0.52; between-group p=0.73, r=0.04). Central corneal thickness remained unchanged (Group 1: 542±28 μm to 541±29 μm, p=0.71; Group 2: 544±27 μm to 543±28 μm, p=0.76; between-group p=0.71, r=0.04). The mean endothelial cell loss was 0.6±1.2% in Group 1 and 0.3±1.1% in Group 2 over 6 months, well within the range of normal physiological cell loss (0.6% ).

Continuous intravitreal bevacizumab monotherapy and sequential bevacizumab-aflibercept treatment demonstrate equivalent short-term safety profiles regarding corneal endothelial function in treatment-naïve nAMD patients. Both regimens produced no clinically or statistically significant alterations in endothelial cell density, morphology, or corneal thickness over 6 months of monthly injections, supporting the corneal endothelial safety of these anti-VEGF therapeutic approaches. The observed minimal cell loss (<1%) in both groups falls within normal physiological ranges and does not differ from age-related endothelial cell decline. These findings provide reassuring evidence for ophthalmologists regarding anterior segment safety .