Importance: Diabetic retinal neurodegeneration precedes vascular changes associated with diabetic retinal disease (DRD). Studies in adults with type 1 diabetes (T1D) show there is retinal layer thinning with DRD, yet there are limited data in youth with T1D. Objectives: To determine if retinal layer thickness changes on optical coherence tomography (OCT) imaging were associated with glycemic outcomes and DRD in youth. Design, Setting, and Participants: This prospective cohort study was conducted at an academic pediatric diabetes center among youth with T1D aged 9 to 21 years participating in the ACCESS2 (AI for Pediatric Diabetic Eye Exams Study 2) study. Participants were enrolled and data were collected July 11, 2022, and April 30, 2025. Data analysis was performed from June 2025 through October 2025. Exposure: OCT imaging. Main Outcomes and Measures: The primary outcome was macular OCT volumes, which were segmented by the Topcon Maestro camera software and reviewed by the Wisconsin Reading Center for 3 neuroretinal layers: (1) retinal nerve fiber layer (RNFL) thickness, (2) ganglion cell and inner plexiform layer (GCL+IPL) thickness, and (3) GCL+IPL+RNFL thickness, as well as total retinal thickness. Layer thicknesses were analyzed for associations with glycemic outcomes and DRD and for potential covariates. Results: A total of 294 youth with T1D (n = 578 eyes), among whom mean (SD) age was 15.8 (2.8) years, 153 participants (52.0%) were female, and 108 participants (36.7%) had public insurance, were included. Participants had a median (IQR) duration of diabetes of 7.0 (4.6-10.1) years and a median (IQR) hemoglobin A1c (HbA1c) of 8.5% (7.5%-9.9%); 210 participants (71.4%) used an insulin pump. Of the total 578 eyes, 65 eyes (11.2%) had mild DRD and 10 eyes (1.73%) had moderate DRD. In adjusted analyses, moderate DRD vs no DRD was associated with RNFL thickness of -1.2 µm (95% CI, -2.9 to 0.5; P = .20), GCL+IPL thickness of -1.2 µm (95% CI, -2.8 to 0.4; P = .19), and outer retinal layer thickness of -0.8 µm (95% CI, -3.9 to 2.2; P = .80). In multivariable models, GCL+IPL and outer retinal layer thickness were associated with HbA1c (β = -0.39; 95% CI, -0.78 to -0.01; P = .04; and β = -0.81; 95% CI, -1.49 to -0.12; P = .02, respectively). Conclusions and Relevance: In this prospective cohort study, neuroretinal layer thinning was observed in youth with T1D without clinically apparent DRD and was associated with higher HbA1c. These findings support elucidating the development of diabetic retinal neurodegeneration and its potential role as a biomarker of retinal vascular disease in youth.
Ramanujam et al. (Thu,) studied this question.