Hyperreflective Foci in Diabetic Macular Edema with Subretinal Fluid: Association with Visual Outcomes after Anti-VEGF Treatment

Introduction: Objectives of the study were to describe the hyperreflective foci (HRF) on optical coherence tomography angiography in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of SRF, the number of HRF in the superficial capillary plexus, deep capillary plexus, and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA, was analyzed. Results: BCVA was significantly improved in DME after anti-VEGF treatment; however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p < 0.001), and SRF height (p < 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p < 0.001). Conclusion: The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment.