Macular Pigment Changes in Patients with Diabetes Mellitus and Without Diabetic Retinopathy.

INTRODUCTION: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and a leading cause of vision impairment in developed countries. Macular pigment optical density (MPOD) assessment provides a non-invasive method for evaluating in vivo changes in macular pigment. In this study, we investigated macular pigment alterations in eyes of patients with type 2 DM without clinically detectable DR using an autofluorescence-based MPOD (AF-MPOD) technique. METHODS: This was an observational, cross-sectional study including patients with type 2 DM without signs of DR and age- and gender-matched healthy controls. Confocal autofluorescence-based MPOD imaging was used to quantify macular pigment changes within the central 6.0° eccentricity. Retinal structural and microvascular alterations were also assessed using optical coherence tomography (OCT) and OCT angiography (OCTA). The primary outcome measure was the quantitative assessment of AF-MPOD parameters. Secondary outcomes included the evaluation of OCT and OCTA alterations and the exploratory identification of distinct imaging phenotypes among diabetic patients. RESULTS: Forty eyes from patients with type 2 DM and 40 control eyes were included. Eyes from patients with DM showed significantly reduced AF-MPOD parameters and lower OCTA vessel density compared with healthy control eyes (all adjusted p < 0.001). Inner retinal thinning was also observed. Glycemic control was inversely associated with AF-MPOD values and vessel density, whereas higher body mass index showed strong associations with AF-MPOD reduction. AF-MPOD parameters remained independently associated with OCTA-derived vascular metrics after multivariable adjustment. CONCLUSIONS: Our findings suggest that an early, interconnected neurovascular-metabolic retinal dysfunction may be detectable before the onset of clinically visible DR. AF-MPOD assessment may provide complementary imaging information on early retinal involvement in DM and warrants further validation in longitudinal studies. CLINICAL TRIAL REGISTRATION: Protocol ID: PNRR-MAD-2022-12376008; ClinicalTrials.gov Identifier: NCT06582472.