Short-Term Corneal Endothelial Safety Of Intravitreal Anti-Vegf Therapy In Diabetic Macular Edema: A Prospective Randomized Comparative Study Of Bevacizumab Versus Sequential Bevacizumab-Aflibercept Treatment

To prospectively compare the effects of continuous intravitreal bevacizumab monotherapy versus sequential bevacizumab-aflibercept treatment on corneal endothelial cell density, morphology, and central corneal thickness in treatment-naïve diabetic macular edema (DME) patients, a population with inherently increased susceptibility to endothelial dysfunction due to diabetic keratopathy.

Department of Ophthalmology, Recep Tayyip Erdogan University Training and Research Hospital, Rize, Turkey. Prospective, randomized, parallel-group comparative study.

Seventy treatment-naïve DME eyes from 70 type 2 diabetic patients (age ≥40,  were randomized 1:1. Group 1 (n=35): monthly intravitreal bevacizumab 1.25 mg for 6 consecutive months. Group 2 (n=35): monthly bevacizumab1.25 mg for months 1-3, then monthly aflibercept 2.0 mg for months 4-6. DME confirmed by OCT(CST ≥300 μm). Exclusion criteria: prior anti-VEGF or laser treatment, intraocular surgery within 6 months, corneal dystrophy, proliferative DR requiring PRP, contact lens use, glaucoma, baseline ECD <2000 cells/mm². Non-contact specular microscopy  performed by a single masked examiner at baseline, 3 and 6 months assessed: endothelial cell density(ECD), coefficient of variation(CV), hexagonality(HEX%), and central corneal thickness(CCT).

Seventy eyes completed 6-month follow-up (mean age 61.4±8.2 years; mean diabetes duration 12.8±5.6 years; mean HbA1c 7.9±1.4%). Baseline endothelial cell density (ECD) was lower than age-matched non-diabetic values (2489±140 vs ~2650 cells/mm²), indicating subclinical diabetic keratopathy. Group 1 showed a non-significant ECD reduction from 2487±142 to 2468±148 cells/mm² at 6 months (0.8% loss; p=0.24), while Group 2 decreased from 2491±138 to 2477±144 cells/mm² (0.6% loss; p=0.41), with no between-group difference (p=0.38). HEX, CV  and CCT Remained stable in both groups. Patients with HbA1c ≥8% showed a trend toward greater ECD loss compared to those with better glycemic control .

Seventy eyes completed 6-month follow-up. Baseline endothelial cell density (ECD) in diabetic patients was lower than age-matched non-diabetic values (2489±140 vs ~2650 cells/mm²), indicating subclinical diabetic keratopathy. Both groups showed minimal, non-significant ECD reduction at 6 months (Group 1: 0.8% loss, p=0.24; Group 2: 0.6% loss, p=0.41), with no between-group difference (p=0.38). Hexagonality, coefficient of variation, and central corneal thickness remained stable. Patients with HbA1c ≥8% showed a trend toward greater ECD loss (p=0.07). Diabetes duration correlated negatively with baseline ECD (r=-0.28; p=0.019).