We read with great interest the recent article by Yan et al evaluating peripapillary retinal and choroidal vasculature in patients with diabetes of different durations but without clinically detectable diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA).1 Their study is noteworthy because it shifts attention from the macula to the peripapillary neurovascular–choroidal complex and shows that peripapillary superficial capillary plexus vascular density (SCP pVD) is reduced in diabetic eyes even before clinically visible DR becomes apparent. In addition, SCP pVD was independently associated with diabetes duration, peripapillary retinal nerve fiber layer (pRNFL) thickness, peripapillary choroidal thickness, and hypertension, underscoring the potential relevance of the peripapillary region as an early site of diabetes-related ocular injury.

From an endocrinology perspective, however, these findings may be more appropriately interpreted as a marker of cumulative diabetes-related microvascular burden rather than a DR-specific preclinical biomarker alone. In the multivariable model, hypertension remained independently associated with SCP pVD, and the authors also acknowledged that renal function, lipid status, and short-term glycemic fluctuations were not fully controlled.1 This is clinically important because the diabetic eye is not an isolated vascular bed: peripapillary OCTA abnormalities may reflect broader systemic endothelial dysfunction and microvascular aging, rather than a retina-specific trajectory toward DR alone.

A second point concerns glycemic interpretation. Yan et al found that fasting blood glucose and HbA1c were not significant determinants of SCP pVD, whereas diabetes duration was an independent predictor.1 This should not be read as evidence that glycemic exposure is unimportant. Rather, it likely reflects the limitation of single time-point glycemic metrics in a cross-sectional design. The concept of metabolic memory suggests that microvascular injury is shaped by cumulative and historical glycemic burden, not merely by a contemporaneous HbA1c value.1 In this sense, diabetes duration may function as a crude surrogate for long-term exposure, although future work would benefit from longitudinal HbA1c trajectories, time-in-range, and glycemic variability.

We also believe the structural conclusions should be phrased with some caution. The study convincingly supports a duration-related decline in SCP pVD and pRNFL-related changes, which is biologically plausible and consistent with prior work suggesting that retinal neurodegeneration may precede overt microvascular retinopathy,2 as well as longitudinal evidence of progressive retinal nerve fiber and choroidal alterations in diabetes.3,4 However, within the diabetes-duration subgroups, choroidal parameters such as pCT, pCVV, and pCVI did not remain significantly different after statistical adjustment in the main subgroup analysis.1 Accordingly, the choroidal findings may currently be better framed as suggestive trends rather than definitive duration-stratified progression markers.

The most compelling translational implication of this work, in our view, is not immediate treatment escalation, but risk enrichment. Patients with long-standing diabetes and a normal fundus examination may still harbor quantifiable subclinical ocular microvascular injury. At present, these data support closer surveillance and more integrated systemic–ocular risk assessment in selected high-risk patients, rather than immediate OCTA-guided therapeutic decision-making. Prospective multicenter studies incorporating OCTA, renal biomarkers, cumulative glycemic exposure, and functional visual endpoints will be essential before peripapillary parameters can be adopted as clinically actionable biomarkers.

Overall, Yan et al provide valuable evidence that the peripapillary microenvironment is altered before clinically apparent DR develops. We believe the greatest strength of this study lies in highlighting an ocular signature of cumulative microvascular stress, which may ultimately help refine early risk stratification in diabetes.

Data sharing is not applicable to this article as no data were created or analysed in this study.

MC: Conceptualization, Writing – original draft, Writing – review and editing.

QC: Conceptualization, Writing – review and editing.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

There is no funding to report.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

1. Yan M, Zhang WJ, Chen C, et al. Peripapillary retinal and choroidal vasculature in patients with diabetes of different durations without clinical diabetic retinopathy. Diabetes Metab Syndr Obes. 2026;19:563069. doi:10.2147/DMSO.S563069

2. Sohn EH, van Dijk HW, Jiao C, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A. 2016;113(19):E2655–2. doi:10.1073/pnas.1522014113

3. Lee MW, Lim HB, Kim MS, et al. Effects of prolonged type 2 diabetes on changes in peripapillary retinal nerve fiber layer thickness in diabetic eyes without clinical diabetic retinopathy. Sci Rep. 2021;11(1):6813. doi:10.1038/s41598-021-86306-y

4. Hui Z, Guo X, Bulloch G, et al. Rates of choroidal loss and ganglion cell-inner plexiform layer thinning in type 2 diabetes mellitus and healthy individuals: a 2-year prospective study. Br J Ophthalmol. 2023;108(1):84–90. doi:10.1136/bjo-2022-321603