To compare the association of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) therapies on lower extremity vascular complications and mortality in PAD. We conducted a retrospective cohort study using a nationwide U.S. electronic health records database. Adults with PAD and type 2 diabetes who initiated GLP-1RA, SGLT2i, or DPP4i therapy (May 2013-January 2025) were included. Propensity score matching (1:1) balanced baseline characteristics. Cox models estimated hazard ratios (HR) with 95 % confidence intervals (CI) for major amputation (primary outcome), lower extremity revascularization (LER), and all-cause mortality over 3 years follow-up. Subgroup analyses included symptomatic PAD, prior LER, and drug-level comparisons. GLP-1RAs were associated with lower risks of major amputation (HR 0.79 [95 % CI 0.70-0.90]), LER (HR 0.82 [0.76-0.88]), and mortality (HR 0.71 [0.68-0.73]) compared with SGLT2i (n = 77,393 each). Similar reductions were seen versus DPP-4is (n = 39,907 each); SGLT2is and DPP-4is showed comparable risks (n = 42,924 each). GLP-1RA benefits remained significant in symptomatic PAD (p < 0.05) and were associated with lower mortality in LER patients (p < 0.05). Semaglutide and tirzepatide showed the greatest benefit. GLP-1RAs were associated with lower limb complication and mortality risks in PAD, supporting a potential vascular benefit that warrants prospective evaluation.

Retinitis pigmentosa (RP) is the most common inherited retinal disease and a major cause of irreversible vision loss. The purpose of this study was to assess peripheral retinal vessels in RP. A cross-sectional study. Patients with RP and age-matched controls. Using ultra-widefield fundus images, the retina was divided into 3 zones: posterior, midperiphery, and far periphery. To evaluate vascularity of the retina, the vessels were counted at the border of posterior and midperipheral zones (Z1/2) and the border of midperipheral and far peripheral zones (Z2/3). Vessel counts at Z1/2 and Z2/3. One hundred eighty-one eyes of 107 RP patients and 130 eyes of 84 controls were included. In the RP group, the median vessel counts at Z1/2 and Z2/3 were 8 and 3, respectively. These were strikingly lower than the control group with the median vessels of 42 and 43.5 at Z1/2 (P < 0.001) and Z2/3 (P < 0.001), respectively. Twenty-two percent of RP eyes were entirely avascular in the far periphery, and 7% were avascular in the midperiphery and far periphery. Only 5% of RP eyes had >25 vessels at Z2/3. There were significantly fewer vessels in the temporal retina at both Z1/2 (P = 0.01) and Z2/3 (P < 0.001) in RP eyes. Furthermore, eyes with visual acuity of 20/200 or worse had significantly fewer vessels at Z1/2 (P < 0.001) and Z2/3 (P < 0.001). There were no significant differences in the number of vessels at Z1/2 and 2/3 between the right and left eyes of RP patients with both eyes included in the study. This study provides compelling evidence of substantial symmetrical peripheral retinal vascular loss in RP. This finding may aid in clinical diagnosis of the disease and have significant therapeutic implications. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective: To evaluate the long-term impact of social determinants of health on diabetic retinopathy (DR) incidence, complications, and management in patients with type 2 diabetes mellitus (T2DM), with emphasis on disparities among treatment-adherent individuals and demographic subgroups. Methods: We conducted a retrospective cohort study using TriNetX, a national electronic health records network spanning 70 U.S. healthcare organisations. Adults diagnosed with T2DM were categorised into socially deprived and non-deprived cohorts based on ICD-10 codes related to housing instability, food insecurity, and financial hardship. Propensity score matching balanced cohorts on demographics, comorbidities, laboratory values, medications, and ophthalmic care utilisation. Outcomes included incident DR, sight-threatening complications, ophthalmic treatment and diagnostics, and documented treatment nonadherence. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Matched cohorts included 62,786 socially deprived and 62,786 non-deprived patients (mean age, 54 years; 42% female; 49% White, 27% Black, 14% Hispanic). Over a 10-year follow-up, social deprivation was associated with increased risk of DR (HR 1.40, 95% CI 1.34–1.47) and sight-threatening complications, including blindness. Documented nonadherence was significantly increased in the socially deprived cohort (HR 3.57, 95% CI 3.47–3.68). Among patients without documented nonadherence, social deprivation was associated with increased DR risk (HR 1.44, 95% CI 1.35–1.54) and treatment utilisation. Disparities were most pronounced in males, Hispanic individuals, and adults aged 18–39. Conclusions: Social deprivation, regardless of documented treatment adherence, increased DR incidence and complications. Targeted interventions are needed to address persistent disparities and reduce DR burden.