Evidence for Photoreceptor Oxidative Stress Detected by OCT Biomarkers in Patients at the Earliest Stage of Diabetic Retinopathy

Abstract

Purpose : It is unclear if oxidative stress in the outer retina occurs early in patients at the beginning of non-proliferative diabetic retinopathy (DR), the hypothesis examined herein.

Methods : Twelve patients with type 2 diabetes, little to mild non-proliferative DR and no macular edema underwent standard ophthalmic clinical evaluation and OCT. From each OCT, we examined the foveola, fovea, parafovea, perifovea, and peripheral retina and measured two oxidative stress-linked biomarkers: i) the mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), and ii) the external limiting membrane to retinal pigment epithelium thickness (ELM-RPE). To model the impact of retinal acidification on the OCT biomarkers, 129S6/ev mice were given a single IP injection of acetazolamide (ACZ, carbonic anhydrase inhibitor) or vehicle.

Results : MCP/AR and ELM-RPE thickness were both lower-than-normal in all macular regions in the T2D group. In a companion experimental study involving an ACZ challenge, we tested whether this biomarker pattern is consistent with an oxidative stress / acidification signaling pathway. Indeed, in response to ACZ, non-diabetic mice also showed subnormal MCP/AR and ELM-RPE thickness.

Conclusions : An OCT energy-linked biomarker pattern was identified in patients with type 2 diabetes that appears in-line with an oxidative stress / acidification signaling pathway. We predict that administration of anti-oxidants in future studies will correct these OCT biomarker lesions and confirm the presence of oxidative stress.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.