Differential Changes in Retinal Cyst Characteristics in inner versus outer retina in Diabetic Macular Edema Treated With Ang-2/VEGF-A Dual Inhibitor

Purpose: Location of retinal cysts in diabetic macular edema (DME) can have clinical implications and a layer-specific response to treatment may aid in predicting therapeutic response. This study aimed to compare quantitative and qualitative changes in inner versus outer retinal cysts after loading dose of faricimab in center-involved cystoid DME using spectral-domain OCT (SD-OCT). Methods: 435 retinal cysts (194 inner, 241 outer) from eighteen eyes of 12 patients were analyzed on 612 SD-OCT B-scans within the 1 central mm. Cysts were classified as inner (IC) or outer (OC) based on the location relative to the outer plexiform layer (OPL). Features of the cysts were quantified using ImageJ (1.53), including reflectivity as optical density (ODN), ODN ratio (ODR), area, and circularity index (CI). Non-parametric analyses were performed, with significance set at p < 0.05. Results: Faricimab significantly reduced central retinal thickness (CRT),(p<.01), inner, outer, total cyst area and cyst count (p≤.03, for all). IC showed significant reductions in number, ODN, and CI (p≤.01, for all). OC exhibited a reduction in number (p=.08) and a significant increase in ODN (p=.04). Higher baseline CRT and larger total cyst area were associated with greater %CRT reduction (p=.008 and p=.02), whereas higher baseline OC reflectivity was associated with smaller %CRT reductions (p=.04). Conclusions: Faricimab induces a compartment-specific response of intraretinal cysts in DME. Inner and outer retinal fluid show distinct qualitative behaviour, reflecting different blood–retinal barrier dynamics. OCT-based assessment of cyst location and reflectivity may complement CRT in evaluating treatment response.