Accelerated GCIPL Thinning Observed in Type 2 Diabetes Patients without Retinopathy

The authors of this study argue that monitoring macular ganglion cell-inner plexiform layer (GCIPL) thickness using OCT or OCT-A is crucial for patients with longstanding type 2 diabetes, even in the absence of retinopathy, as GCIPL thinning may indirectly reflect damage to the central nervous system. This image from the study shows (A) GCIPL segmentation on OCT, (B) SCP segmentation in OCT-A, (C) a 6x6mm en-face angiogram of SCP in OCT-A and (D) color en-faceSCP angiogram on OCT-A. Photo: Fan Y, et al. Am J Ophthalmol. September 2025. [Epub ahead of print]. Click image to enlarge. By the time patients with diabetes are diagnosed with diabetic retinopathy (DR), they often face irreversible retinal damage as a result of chronic hyperglycemia, which promotes hypoxia, oxidative stress and inflammation that disrupt the retinal neurovascular unit. Recognizing subclinical signs of DR is an emerging research focus aimed at helping clinicians detect these structural changes early on, ultimately preserving vision and enhancing patient outcomes. A new study investigated subclinical signs of DR in type 2 diabetes patients over a two-year period, specifically examining neural and microvascular changes before clinical diagnosis. Its authors observed accelerated changes in macular ganglion cell-inner plexiform layer thickness (GCIPLT) among non-DR patients, indicating that neurodegeneration may precede microvascular alterations prior to DR diagnosis.The study recruited 282 eyes, including 141 from type 2 diabetes patients without clinical retinopathy and 141 from age- and sex-matched healthy controls in China. At baseline and two-year follow-up, researchers used OCT and OCT-A to measure GCIPLT, retinal thickness and superficial capillary plexus (SCP) vessel density. Using linear mixed-effects models, they estimated the rates of change and compared the two groups.The data indicated significant reductions in GCIPT and the ratio of GCIPT to retinal thickness in the non-DR group, with GCIPLT decreasing by -0.229μm/year and 0.324%—a rate approximately five times faster than that seen in controls. After accounting for confounding factors, the longitudinal rates of retinal thickness, GCIPLT and GCIPLT/retinal thickness were notably accelerated in type 2 diabetes patients without DR compared to healthy controls, decreasing by -0.603μm/year, -0.189 μm/year and -0.073%, respectively. However, longitudinal changes in SCP vessel density revealed no significant differences between the two groups, supporting the study’s hypothesis that neurodegenerative changes occur before microvascular alterations in patients with type 2 diabetes.In their paper on the findings, published in American Journal of Ophthalmology, the researchers suggested, “The detection of retinal neurodegeneration through OCT may serve as a potential precursor to subsequent microvascular pathology.” Moreover, they noted that while patients with type 2 diabetes in this study exhibited progressive GCIPL thinning below the rate reported in previous studies (-0.229μm per year), “the cumulative thinning caused by diabetic retinal neurodegeneration may become comparable to that observed in moderate-stage glaucoma over a period of 10 to 20 years.” Monitoring GCIPL thinning in these patients could provide a convenient and noninvasive method that serves as an indirect reflection of central nervous system damage, they suggested.In the future, the study authors say they hope to perform longer-term studies with closer follow-up to “determine whether GCIPL thinning is a risk factor for the onset and progression of DR and whether it can predict the risk of DR development.” They added, “Future studies could also examine the structural-functional correlations of deep capillary plexus, compare the thinning of GCIPL and outer retinal layers, and focus more on parameters in the peripapillary region.”Click here for the journal source. Fan Y, Li L, Wu X, et al. Longitudinal neural and microvascular changes in type 2 diabetic patients without retinopathy: a 2-year prospective cohort study. Am J Ophthalmol. September 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.