Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score.

PURPOSE: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. DESIGN: This was a retrospective study using data from the Women's Health Initiative. METHODS: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. RESULTS: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). CONCLUSIONS: Independent of the CDR GRS, women with large CDR had a lower cognitive function.

Probabilistic Forecasting of Anti-VEGF Treatment Frequency in Neovascular Age-Related Macular Degeneration.

Purpose: To probabilistically forecast needed anti-vascular endothelial growth factor (anti-VEGF) treatment frequency using volumetric spectral domain-optical coherence tomography (SD-OCT) biomarkers in neovascular age-related macular degeneration from real-world settings. Methods: SD-OCT volume scans were segmented with a custom deep-learning-based analysis pipeline. Retinal thickness and reflectivity values were extracted for the central and the four inner Early Treatment Diabetic Retinopathy Study (ETDRS) subfields for six retinal layers (inner retina, outer nuclear layer, inner segments [IS], outer segments [OS], retinal pigment epithelium-drusen complex [RPEDC] and the choroid). Machine-learning models were probed to predict the anti-VEGF treatment frequency within the next 12 months. Probabilistic forecasting was performed using natural gradient boosting (NGBoost), which outputs a full probability distribution. The mean absolute error (MAE) between the predicted versus actual anti-VEGF treatment frequency was the primary outcome measure. Results: In a total of 138 visits of 99 eyes with neovascular AMD (96 patients) from two clinical centers, the prediction of future anti-VEGF treatment frequency was observed with an accuracy (MAE [95% confidence interval]) of 2.60 injections/year [2.25-2.96] (R2 = 0.390) using random forest regression and 2.66 injections/year [2.31-3.01] (R2 = 0.094) using NGBoost, respectively. Prediction intervals were well calibrated and reflected the true uncertainty of NGBoost-based predictions. Standard deviation of RPEDC-thickness in the central ETDRS-subfield constituted an important predictor across models. Conclusions: The proposed, fully automated pipeline enables probabilistic forecasting of future anti-VEGF treatment frequency in real-world settings. Translational Relevance: Prediction of a probability distribution allows the physician to inspect the underlying uncertainty. Predictive uncertainty estimates are essential to highlight cases where human-inspection and/or reversion to a fallback alternative is warranted.

GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence.

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies. Nuclear localization of GPX1 was also observed in both primary prostate epithelial cells and the immortalized prostate-derived cell line RWPE-1, but not in LNCaP or PC3 prostate tumor-derived cell lines. Quantification of GPX1 levels in the entire cell, the cytoplasm, and the nucleus did not indicate any association of either its levels or subcellular distribution with prostate cancer recurrence. While GPX1 levels may not have an impact on survival among men with prostate cancer, the data indicates that this extensively characterized protein may have a novel function in the nucleus of prostate epithelial cells.