Association between Hyperreflective Foci in the Outer Retina, Status of Photoreceptor Layer and Visual Acuity in Diabetic Macular Edema Running title: Hyperreflective foci, photoreceptor layer, and VA in DME

PURPOSE To determine if hyperreflective foci in the outer retina are associated with photoreceptor integrity and the logarithm of minimal angle of resolution (logMAR) visual acuity (VA) in patients with diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. METHODS Patients (n=76; 108 eyes) with clinically relevant macular edema and no serous retinal detachment were analyzed retrospectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained for all patients. We investigated the relationship between the hyperreflective foci in the outer retinal layers of the external limiting membrane (ELM) at the fovea and the photoreceptor integrity and VA. RESULTS SD-OCT showed that 58 eyes (53.7%) had hyperreflective foci in the outer retinal layers, and 107 eyes (99.1%) had hyperreflective foci in the inner retinal layers. The logMAR VA was significantly (P<.0001) worse in eyes with hyperreflective foci in the outer retinal layers than in eyes without them (0.463±0.382 vs 0.127±0.206, respectively). Disruption of the ELM line on OCT was significantly (P<.0001, for both comparisons) associated with both hyperreflective foci in the outer retinal layers and poor logMAR VA. Disruption of the junction of the inner and outer segment line (IS/OS) also was related to hyperreflective foci in the outer retinal layers and poor logMAR VA (P<.0001 for both comparisons). CONCLUSIONS The presence of hyperreflective foci in the outer retina is closely associated with a disrupted ELM and IS/OS line on SD-OCT images and decreased VA in DME.