Use of faricimab for refractory diabetic macular edema in real-world clinical practice: When anatomical success meets functional limits

Abstract

Objective To evaluate the anatomical and functional outcomes of faricimab in the treatment of naïve and refractory diabetic macular edema (DME) and to investigate OCT biomarkers associated with visual outcomes. Methods This retrospective real-world study included eyes with DME treated with faricimab. All eyes received three loading injections followed by a treat-and-extend regimen. The primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcomes included changes in OCT biomarkers, including intraretinal cysts (IRCs), subretinal fluid (SRF), hyperreflective foci (HRFs), disorganization of the retinal inner layers (DRIL), and external limiting membrane/ellipsoid zone (ELM/EZ) disruption. Changes in BCVA, CMT, and OCT biomarkers were analyzed using generalized estimating equations (GEEs). A multivariable GEE model was used to identify factors independently associated with 12-month BCVA. Results A total of 110 eyes from 104 patients were included. At 12 months, the CMT significantly decreased in both the naïve and refractory groups (both P < 0.001). BCVA significantly improved in naïve eyes (P = 0.003), whereas visual improvement was limited in refractory eyes (P = 0.390). Both groups showed significant reductions in the proportions of eyes with IRCs, SRF, and HRFs (all P < 0.001). Refractory eyes had higher proportions of baseline DRIL and ELM/EZ disruption (both P < 0.001). In the multivariable GEE model, baseline DRIL (B = 0.044; 95% CI: 0.004 to 0.084; P = 0.031) and ELM/EZ disruption (B = 0.147; 95% CI: 0.069 to 0.225; P < 0.001) remained independently associated with poor 12-month BCVA, whereas the treatment group was not independently associated with 12-month BCVA (P = 0.969). Conclusion Faricimab achieved effective retinal fluid control in both naïve and refractory DME. However, visual recovery was associated with baseline retinal microstructural integrity, with DRIL and ELM/EZ disruption independently associated with poorer 12-month visual outcomes beyond conventional anatomical parameters. In eyes with refractory DME and limited visual improvement, sustained fluid control and reduced treatment burden may remain clinically meaningful outcomes.