Evaluation of anti-VEGF response in diabetic macular edema patients with baseline DRIL: a multicenter real-world study (BOSPHORUS-DME Study Group Report No.16)

To evaluate the functional and anatomical outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve diabetic macular edema (DME) eyes exhibiting disorganization of the retinal inner layers (DRIL) at baseline, and to examine associations between DRIL and systemic or imaging biomarkers in a large multicenter real-world cohort.

This multicenter retrospective cohort study included 221 eyes with baseline DRIL among 1321 treatment-naïve DME eyes followed at eight tertiary centers in Türkiye. All eyes initially received a bevacizumab loading dose, followed by a pro re nata (PRN) regimen with bevacizumab, aflibercept, or ranibizumab according to clinical response. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and DRIL status were assessed using spectral-domain OCT at baseline and at months 3, 6, and 12.

Mean BCVA and CMT improved significantly at 12 months across all treatment groups (p < 0.001). In univariate analyses, eyes switched to aflibercept showed superior functional (0.58 logMAR) and anatomical (370.7 μm) outcomes compared with bevacizumab and ranibizumab (p = 0.039 and p = 0.001, respectively). However, in multivariable regression analyses adjusting for baseline characteristics and treatment intensity, anti-VEGF agent type was not independently associated with outcomes. Baseline DRIL was negatively correlated with BCVA and CMT improvement and positively correlated with systemic lipid parameters (p < 0.01).

In this large real-world multicenter study, anti-VEGF therapy provided meaningful anatomical and functional improvements in DRIL-positive DME eyes. Although aflibercept appeared superior in univariate analyses, this difference was not sustained after adjustment, indicating that baseline characteristics rather than treatment selection may be the primary determinants of outcome. Unlike prior studies that focused primarily on corticosteroids, this study provides one of the largest datasets evaluating anti-VEGF efficacy in DRIL-positive eyes. Findings underscore DRIL as a strong prognostic OCT biomarker with potential to guide individualized treatment planning and optimize therapeutic outcomes in DME.