Retinal neurodegeneration is a hallmark of many vision-threatening diseases, and the receptor sortilin has emerged as a promising therapeutic target due to its involvement in p75NTR-associated neurodegenerative signaling. The effect of sortilin inhibition on acute inner retinal neurodegeneration induced by optic nerve crush was therefore investigated. Pharmacological sortilin inhibition using intravitreal delivery was evaluated in C57BL/6JRj male mice subjected to unilateral crush. Furthermore, the effect of constitutive sortilin deficiency was examined using Sort1-/- mice, and changes in sortilin, p75NTR, and associated injury markers were analyzed. Neither pharmacological inhibition nor constitutive loss of sortilin protected against inner retinal thinning or retinal ganglion cell loss following optic nerve crush. A transient 1.4-fold increase in p75NTR mRNA was observed early after injury, accompanied by a two-fold increase in protein levels. While sortilin expression remained largely unchanged, sortilin deficiency was associated with an altered baseline retinal state. Following optic nerve crush, the induction of p75NTR was significantly attenuated in sortilin-deficient retinas. In summary, sortilin inhibition does not preserve inner retinal structure following optic nerve crush, but alters molecular markers associated with glial activation, inflammatory signaling, and neurotrophin-related pathways. Sortilin-dependent pathways may be more relevant in disease contexts characterized by chronic stress and neuroinflammation.
This prospective observational cohort study aimed to identify predictive factors for the progression of ganglion cell-inner plexiform layer (GCIPL) thinning in patients with Type 2 diabetes mellitus (T2DM). In total, 2,123 consecutive patients with T2DM were included and followed up for three years. All participants underwent 3 mm & times; 3 mm optical coherence tomography (OCT) imaging centered on the macula. After image quality control, data from 1,500 patients (1,500 eyes) were analyzed. Longer baseline axial length (AL), higher baseline intraocular pressure, poorer baseline best corrected visual acuity (BCVA), greater baseline macular retinal thickness, greater baseline macular GCIPL thickness, and a wider glycated hemoglobin (HbA1c) fluctuation range were associated with a higher rate of decline in GCIPL (p < 0.001). In the final multivariate regression model, longer AL (beta = -0.187; 95% confidence interval [CI]: -0.255 to -0.120 mm/year; p < 0.001), poorer baseline BCVA (beta = -0.201; 95% CI: -0.271 to -0.130; p < 0.001), greater baseline macular retinal thickness (beta = -0.126; 95% CI: -0.198 to -0.054 mu m/year; p = 0.001), greater baseline macular GCIPL thickness (beta = -0.305; 95% CI: -0.376 to -0.235 mu m/year; p < 0.001), and more microalbuminuria (beta = -0.069; 95% CI: -0.136 to -0.002 mg/ml/year; p = 0.045) were independently associated with a higher rate of GCIPL decline. These factors are major predictors of GCIPL loss in T2DM and should be considered when interpreting GCIPL measurements in clinical practice and research.
Early identification of vision-threatening diabetic retinopathy (VTDR) is critical to prevent visual impairment in patients with type 2 diabetes mellitus (T2DM). This multicenter prognostic study first conducted a meta-analysis of published VTDR predictors and subsequently developed and externally validated logistic regression-based nomograms to stratify VTDR risk using readily available systemic variables that can be collected by non-specialists. A meta-analysis of 29 published studies involving diverse populations with T2DM identified candidate predictors. Using a development cohort of 1,633 T2DM patients without baseline VTDR and an independent external validation cohort of 1,277 patients, four nomograms were constructed and evaluated by area under the curve (AUC), calibration plots, and decision curve analysis. The optimal model incorporated four routinely available variables, including diabetes duration, hematocrit (HCT), glycated hemoglobin (HbA1c), and urinary albumin-to-creatinine ratio (UACR) stage, and demonstrated robust discrimination, with an AUC of 0.812 (95% CI, 0.785-0.839) in the development cohort and 0.790 (95% CI, 0.756-0.824) in the validation cohort. Calibration plots showed strong agreement between predicted and observed risk, and decision curve analysis confirmed superior clinical net benefit. The optimal model (Model 2) achieved this predictive performance with only four routinely accessible predictors, highlighting its parsimony and practicality for broad implementation in primary care and resource-limited settings. This evidence-based nomogram, derived from a meta-analysis of 29 studies and rigorously validated in two independent Chinese cohorts, enables reliable VTDR risk stratification using only routine systemic variables. Without requiring specialized ophthalmic examinations, it may assist non-ophthalmic clinicians in identifying high-risk individuals, facilitating timely referral and targeted interventions to reduce preventable vision loss.
To investigate the short-term neurovascular and structural effects of a single instillation of 0.01% atropine in pseudophakic eyes of myopic children. This retrospective repeated measures study enrolled 29 children aged 6-12 years with 44 pseudophakic eyes. All eyes received a single topical instillation of 0.01% atropine. Swept-source optical coherence tomography (OCT)/OCT angiography (OCTA) imaging of the anterior and posterior segments was performed at baseline, 1 and 24 h. Anterior segment parameters, macular neural thicknesses, retinal vascular density, foveal avascular zone (FAZ), and choroidal structural and vascular parameters were analyzed. Intraocular pressure and axial length were also measured. Intraocular pressure and pupil diameter (PD) increased slightly at 1 h, whereas the anterior chamber angle area changed over time (all p < 0.05), with the parameters returning to baseline by 24 h. No significant changes were observed in anterior chamber depth or corneal thickness (both p > 0.05). Retinal vascular density remained largely stable, with a few isolated sector-specific differences. The ganglion cell complex, retinal nerve fiber layer, ganglion cell-inner plexiform layer, and FAZ showed no significant changes (all p > 0.05). The average choroidal thickness in the inferior, temporal, and nasal regions demonstrated a transient decrease at 1 h, with recovery by 24 h. Choroidal vascular volume (CVV) and stromal volume exhibited similar trends in certain regions, whereas the choroidal vascularity index (CVI) remained stable. The change in PD was positively correlated with changes in CVV and CVI in some regions (both p < 0.05). In conclusion, a single instillation of 0.01% atropine did not induce clinically significant adverse changes in the anterior segment's anatomy or posterior circulation parameters in pseudophakic children with myopia, suggesting favorable short-term safety in this population.
