Photoreceptor Layer Thinning May Serve as Noninvasive Biomarker of Early Diabetes

A large UK Biobank study recently determined that structural damage to the photoreceptor outer segment (POS) may indicate early stages of type 2 diabetes. Bolstering these findings, a prospective analysis using optical coherence tomography identified a correlation between POS thinning and increased diabetes risk, providing further evidence that this novel biomarker could aid in earlier detection. The study included 35,024 individuals aged 40 to 69 years from the UK Biobank. Participants underwent comprehensive baseline assessments, which included detailed questionnaires capturing their lifestyle, demographic information and physical measurements, alongside laboratory tests to ascertain diabetes status. OCT imaging was conducted without pupil dilation to examine the thickness of the POS. The analysis focused on assessing how variations in thickness correlated with the incidence of type 2 diabetes over a median follow-up period of 13.2 years. A new study observed that a decrease of 5μm in photoreceptor outer segment thickness was linked to a 10% higher risk of type 2 diabetes. Photo: Daniel Epshtein, OD, Maria Canellos, DO, and Christina Canellos, OD. Click image to enlarge. The results revealed a strong association between photoreceptor layer thinning and increased diabetes risk, which remained significant even after adjusting for various demographic and lifestyle factors. Specifically, a reduction of just 5μm in POS thickness was linked to a 10% increased risk of developing diabetes, with individuals within the lowest category of POS thickness facing a 22% heightened risk compared to those in the highest category. For advice on improving your OCT interpretation skills, see this recent feature. Furthermore, the researchers found that integrating POS thickness measurements into traditional risk models improved the predictive accuracy, indicated by a net reclassification improvement of 0.0356. As they explained in their paper, recently published in the journal Eye, “This relationship underscores the retina’s sensitivity to diabetes beyond observable blood sugar changes,” highlighting the potential of retinal imaging to aid type 2 diabetes screening and diagnosis.While the study authors relay that the precise mechanisms behind photoreceptor outer segment thinning in diabetes are not entirely understood, several contributing factors have been proposed. Hyperglycemia is thought to play a significant role, similar to the neurodegenerative changes seen in type 1 diabetes, they explained. Furthermore, insulin resistance, a hallmark of diabetes, may exacerbate neurodegeneration and is linked to chronic low-grade systemic inflammation, which can increase blood-brain barrier permeability and further retinal degradation. It’s also possible that insufficient mitochondrial biogenesis due to reactive oxygen species generation may leave the photoreceptor layer more vulnerable to the effects of metabolic disorders. The authors noted that further research will help elucidate these and other biological mechanisms.The researchers believe that “POS thinning detected through noninvasive imaging could enable early identification of at-risk individuals,” aiding timely interventions, they concluded in the paper.Click here for the journal source. Ma Y, Wu Y, Hu L, et al. Photoreceptor layer thinning is an early biomarker for type 2 diabetes: a cohort study in UK Biobank. Eye. October 3, 2025. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.