PURPOSE. There is considerable evidence for systemic vascular dysfunction in primary openangle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS.We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 lm, and avascular zones > 100 lm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS.After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR ¼ 2.9; 95% CI, 1.6-5.6), avascular zones (OR ¼ 4.4; 95% CI, 1.7-11.3) and hemorrhages (OR ¼ 12.2; 95% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ‡ 0.43).CONCLUSIONS. These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.

Purpose The purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy. Patients and methods We used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥ 200 microns (μm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models. Results After adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥ 200 μm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤ 0.0001) and in POAG vs controls (P-for trend ≤ 0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend = 0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend = 0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥ 1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score o1.0 (P-for trend = 0.005). Conclusion A high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

Reduced resting nailfold capillary blood flow is present in POAG independent of covariates such as blood pressure, pulse and IOP.

Background Timely allocation of medical resources for coronavirus disease (COVID-19) requires early detection of regional outbreaks. Internet browsing data may predict case outbreaks in local populations that are yet to be confirmed. Objective We investigated whether search-engine query patterns can help to predict COVID-19 case rates at the state and metropolitan area levels in the United States. Methods We used regional confirmed case data from the New York Times and Google Trends results from 50 states and 166 county-based designated market areas (DMA). We identified search terms whose activity precedes and correlates with confirmed case rates at the national level. We used univariate regression to construct a composite explanatory variable based on best-fitting search queries offset by temporal lags. We measured the raw and z-transformed Pearson correlation and root-mean-square error (RMSE) of the explanatory variable with out-of-sample case rate data at the state and DMA levels. Results Predictions were highly correlated with confirmed case rates at the state (mean r=0.69, 95% CI 0.51-0.81; median RMSE 1.27, IQR 1.48) and DMA levels (mean r=0.51, 95% CI 0.39-0.61; median RMSE 4.38, IQR 1.80), using search data available up to 10 days prior to confirmed case rates. They fit case-rate activity in 49 of 50 states and in 103 of 166 DMA at a significance level of .05. Conclusions Identifiable patterns in search query activity may help to predict emerging regional outbreaks of COVID-19, although they remain vulnerable to stochastic changes in search intensity.

A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes-and glaucoma-related traits. Design: Cross-sectional study. Methods: We assembled genome-wide association study summary statistics from Europeanderived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (r g) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR). Results: Overall, there was little r g between diabetes-and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (r g =-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (r g ≥0.45; p≤3.0E-04) and between CDR and POAG were high (r g =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (r g range:-0.18-0.11) and non-significant (p≥0.07). Conclusion: These analyses suggest there is limited genetic correlation between diabetes-and glaucoma-related traits.

DH have densitometry profiles comparable to MA and different from RVO, suggesting that DH in glaucoma have an arterial origin.

Drug discovery efforts in Alzheimer’s disease depend increasingly

Purpose To assess microvascular beds in the optic nerve head (ONH), peripapillary tissue, and the nailfold in patients with primary open-angle glaucoma (POAG) versus controls. Methods Patients with POAG (n = 22) and controls (n = 12) underwent swept-source optical coherence tomography angiography of ophthalmic microvasculature and nailfold video capillaroscopy of the hand. The main outcomes were vessel density (VD) and blood flow of the ONH, the peripapillary and the nailfold microvasculatures. Results Patients with POAG were younger than controls (63.5 ± 9.4 vs. 69.9 ± 6.5 years, P = 0.03). Deep ONH VD and blood flow were lower in patients with POAG than controls (39.1% ± 3.5% vs. 43.8% ± 5.7%; 37.8% ± 5.3% vs. 46.0% ± 7.8%, respectively, P < 0.02 for both); similar results were observed with peripapillary VD (37.9 ± 2.6%, 43.4 ± 7.6%, respectively, P = 0.03). Nailfold capillary density and blood flow were lower in patients with POAG than controls (8.8 ± 1.0 vs. 9.8 ± 0.9 capillaries/mm; 19.9 ± 9.4 vs. 33.7 ± 9.8 pL/s, respectively; P < 0.009 for both). After adjusting for age and gender, deep ONH VD and blood flow, peripapillary VD, and nailfold capillary blood flow were lower in POAG than controls (β = −0.04, −0.07, −0.05, −13.19, respectively, P ≤ 0.046 for all). Among all participants, there were positive correlations between deep ONH and nailfold capillary blood flow (Pearson's correlation coefficient r = 0.42, P = 0.02), peripapillary and nailfold capillary density (r = 0.43, P = 0.03), and peripapillary and nailfold capillary blood flow ( r = 0.49, P = 0.01). Conclusions Patients with POAG demonstrated morphologic and hemodynamic alterations in both ophthalmic and nailfold microvascular beds compared to controls. Translational Relevance The concomitant abnormalities in nailfold capillaries and relevant ocular vascular beds in POAG suggest that the microvasculature may be a target for POAG treatment.