Abstract
Background
Diabetic retinopathy (DR) is a primary cause of blindness in the working-age population. Its end-stage complication, neovascular glaucoma (NVG), carries a dismal visual prognosis. Current late-stage diagnostic models severely limit treatment opportunities. This study aims to utilize widefield swept-source optical coherence tomography angiography (WSS-OCTA) to explore the potential of iris microcirculation parameters as diagnostic and therapeutic monitoring biomarkers for NVG.Methods
A total of 250 participants recruited from Qilu Hospital of Shandong University between March 2026 and June 2026 were enrolled and categorized into four groups: healthy controls, patients with type 2 diabetes without diabetic retinopathy (NDR), patients with type 2 diabetic retinopathy (DR), and patients with DR complicated by neovascular glaucoma (DR+NVG). The 12mm×12mm anterior segment iris images obtained by WSS-OCTA were divided into 6 equal-sized sectors: superior (S), supratemporal (ST), inferotemporal (IT), inferior (I), inferonasal (IN) and supranasal (SN) to evaluate changes in pupillary margin iris vessel density (PMIVD) and pupillary margin iris vessel length density (PMIVLD). One-way analysis of variance and correlation analyses were performed to evaluate associations between PMIVD and clinical physiological indices (intraocular pressure, fasting blood glucose, glycated hemoglobin, creatinine and alanine aminotransferase). A paired t-test was performed to assess the difference of PMIVD and IOP before and after anti-VEGF treatment.Results
Our results showed no significant differences in age, creatinine and alanine aminotransferase across the four groups, while fasting blood glucose and glycated hemoglobin levels were significantly higher in the NDR, DR, and DR+NVG groups than in the control group. For PMIVD, significant intergroup differences were identified in the S, ST, I, and SN regions, but not in the IT or IN regions. Specifically, the DR+NVG group had significantly higher vessel density in the S and ST regions compared with the control group, and also showed significantly elevated vessel density in these two regions relative to both the NDR and DR groups. In contrast, the NDR group exhibited significantly reduced vessel density in the I and SN regions versus controls. For PMIVLD, significant elevations in the DR+NVG group across four iris regions (S, ST, I, and SN) were identified, covering more anatomical areas than PMIVD, whereas no significant reductions were observed in the NDR and DR groups relative to controls. No consistent correlation was observed between regional PMIVD and systemic clinical indices in the control, NDR and DR groups. In the DR+NVG group, PMIVD in all six iris regions showed a significant positive correlation with IOP; however, no uniform systemic metabolic or biochemical associations were observed across the cohort. Anti-VEGF treatment significantly reduced PMIVD across all regions, with the most pronounced decreases occurring at those early predilection sites, underscoring both its diagnostic specificity and therapeutic responsiveness.Conclusions
This study systematically characterized an abnormal increase in iris blood flow in DR+NVG patients, indicating that OCTA-derived quantitative parameters may serve as specific biomarkers for NVG diagnosis and therapeutic efficacy monitoring. Future large-scale, prospective studies are warranted to validate the predictive performance of these novel biomarkers, thereby enabling earlier and more precise intervention for sight-threatening complications of DR.