Ellen E. Freeman

Examination of retinal images provides a non-invasive means to assess the body’s microvascular system, with vessel morphology linked to ocular and systemic diseases. QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) is an automated, artificial intelligence-enabled retinal vasculometry system designed for processing large-scale retinal image datasets, including over 4 million images from within the National Health Service, to facilitate epidemiological studies. The system is uniquely capable of extracting useful information from lower quality images, including those which are partially illuminated, enabling analysis of a greater proportion of images. To enhance cross-dataset generalisation of the system from an earlier dataset-tailored approach, this work leverages 26 annotated retinal image datasets spanning diverse demographics, diseases, camera types, and imaging protocols. Evaluation on the external EPIC-Norfolk dataset demonstrates robust performance with F1 scores of 0.8305, 0.8477, 0.8741, 0.9532, and 0.8677 for arteriole, venule, vessel, optic disc, and optic cup segmentation, respectively, and 0.9197 for image quality classification. The cross-dataset generalisation approach demonstrated increased performance for arteriole/venule segmentation and optic disc segmentation. However, improvements in performance were not observed for optic cup segmentation, or for image quality classification. An online tool is provided to support wider adoption and reproducible biomarker research across diverse populations and imaging settings. In addition, the new public CHASE-AV database is introduced for arteriole and venule segmentation.

Background: Despite associations between atrial fibrillation (AF) and cognitive decline independent of stroke, pathways underlying this relationship remain unclear. Inflammatory markers, such as CRP (C‐reactive protein), are associated with blood–brain barrier (BBB) permeability, potentially leading to neuroinflammation and neurodegeneration. We estimated associations of CRP with cognitive impairment and death in aging adults with AF. Methods: Adults aged ≥45 years with prevalent AF and no cognitive impairment were identified from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (N=30 239). Plasma CRP was measured at baseline and cognitive status measured annually using the Six‐Item Screener. Competing risks Cox proportional hazards regression was used to estimate cause‐specific hazard for cognitive impairment (Six‐Item Screener score ≤3). Cognitive trajectories were identified using latent class growth models and adjusted binomial logistic regression used to estimate associations between CRP and cognitive trajectories, with interactions by sex. Results: Among 2109 participants, 285 developed cognitive impairment and 786 died over a median 9‐year follow‐up. A doubling of baseline CRP levels was associated with increased death (hazard ratio [HR], 1.13 [95% CI, 1.08–1.19]) but not incident cognitive impairment (HR, 0.98 [95% CI, 0.91–1.04]). Latent class analyses identified 2 unique cognitive trajectories: 91% had a stable trajectory, while 9% showed progressive decline. Sex‐specific models showed a 9% increased odds of progressive cognitive decline in men (odds ratio, 1.09 [95% CI, 1.01–1.17]) but not women (odds ratio, 1.04 [95% CI, 0.97–1.12]). Conclusions: Higher CRP was associated with cognitive impairment in aging men with AF, highlighting inflammation‐mediated blood–brain barrier dysfunction as a potential pathway linking AF to cognitive decline.

Background: To cross‐sectionally and longitudinally examine whether retinal vessel traits are associated with glaucoma‐related outcomes (glaucoma, cup‐to‐disc ratio [CDR] and intraocular pressure [IOP]) and age‐related macular degeneration (AMD).Methods: Baseline and 3‐year follow‐up data from the 30 097 participants of the Canadian Longitudinal Study on Aging were used. The follow‐up rate was 92%. QUARTZ, a deep learning algorithm, was used to extract data from retinal images including arteriolar and venular diameter, tortuosity and vertical CDR. Glaucoma and AMD were self‐reported. IOP was measured. Multiple linear and logistic regression were used to adjust for demographic, lifestyle and clinical factors.Results: Having wider arterioles was associated with a lower odds of glaucoma (OR = 0.36, 95% CI: 0.20, 0.65) at baseline but there was no association using longitudinal data. Instead, glaucoma at baseline was strongly associated with 3‐year change in arteriolar diameter (β = −0.21, 95% CI: −0.37, −0.05) indicating that the cross‐sectional association may have been due to reverse causality. Using longitudinal data, greater venular tortuosity was associated with a reduced 3‐year development of glaucoma (OR = 0.52, 95% CI: 0.31, 0.87) and a 3‐year reduction in the CDR (β = −0.006, 95% CI: −0.010, −0.002). Wider venular diameter was associated with a higher odds of AMD at baseline (OR = 2.77, 95% CI: 1.50, 5.15) and a higher odds of the 3‐year development of AMD (OR = 4.15, 95% CI: 1.95, 8.82).Conclusions: Understanding the temporal relationship of changes in the retinal microvasculature and the development of eye disease may lead to better treatment and prevention strategies.

To determine the factors cross-sectionally and longitudinally associated with retinal vessel diameter, total area, and tortuosity in the Canadian Longitudinal Study on Aging (CLSA). Of the 30,097 adults between ages 45 and 85 years old in the CLSA Comprehensive Cohort, 26,076 had at least one retinal image gradable by QUARTZ, a deep-learning algorithm that automatically assessed image quality, distinguished between arterioles and venules, and estimated retinal vessel traits over the entire retina. Questions were asked about demographic, lifestyle, and medical factors. Blood pressure, cholesterol, and C-reactive protein were measured. Participants returned for follow-up 3 years later. Multiple linear regression was used to provide adjusted estimates. Current smoking was strongly associated with wider arteriolar and venular diameters and their widening over 3 years (P < 0.05). Current smoking was also associated with a larger arteriolar and venular area and a 3-year increase in venular area (P < 0.05). Obesity was positively associated with venular diameter, total venular area, 3-year change in total venular area, and venular tortuosity (P < 0.05). Diastolic blood pressure was negatively associated with both arteriolar and venular diameter, area, and tortuosity, both cross-sectionally and longitudinally (P < 0.05). Diabetes was associated with wider arteriolar diameters cross-sectionally, and type 1 diabetes was associated with 3-year widening of arteriolar diameters (P < 0.05). This work provides comprehensive information on the factors associated with retinal vessel traits and their change. Factors such as smoking, obesity, blood pressure, and diabetes were longitudinally related to retinal vessel traits, which play a role in the development of eye disease.

The COVID-19 pandemic had significant impacts on the mental and visual health of patients. This cross-sectional, survey-based, multicentric study evaluates the state of mental and visual health among patients with chronic ocular diseases such as glaucoma, neovascular age-related macular degeneration, diabetic retinopathy, or chronic uveitis during the lockdown period of the COVID-19 pandemic. Mental health was assessed using three questionnaires: the Patient Health Questionnaire-9 (PHQ-9), the Impact of Event Scale-Revised (IES-R), and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25). A total of 145 patients completed the questionnaires. The PHQ-9 showed that most respondents (n = 89, 61%) had none or minimal depressive symptoms, while 31 (21%) had mild depressive symptoms, 19 (13%) had moderate depressive symptoms, 5 (3%) had moderately severe depressive symptoms, and 1 (1%) had severe depressive symptoms. Regarding stress surrounding the pandemic, the median IES-R showed mild distress in 16 (11%), moderate distress in 7 (5%), and severe distress in 4 (3%). The COVID-19 pandemic lockdowns had a negative impact on patients’ mental health with close to 20% of the patients reporting at least moderately depressive symptoms and 19% reporting at least mildly distressful symptoms.

Purpose: The purpose of this study was to examine the association of alcohol consumption with intraocular pressure (IOP) and glaucoma and to assess whether any associations are modified by a glaucoma polygenic risk score (PRS). Methods: Cross-sectional analysis of data from the Canadian Longitudinal Study on Aging Comprehensive Cohort, consisting of 30,097 adults ages 45 to 85 years, was done. Data were collected from 2012 to 2015. Alcohol consumption frequency (never, occasional, weekly, and daily) and type (red wine, white wine, beer, liquor, and other) were measured by an interviewer-administered questionnaire. Total alcohol intake (grams/week) was estimated. IOP was measured in mm Hg using the Reichert Ocular Response Analyzer. Participants reported a diagnosis of glaucoma from a doctor. Logistic and linear regression models were used to adjust for demographic, behavioral, and health variables. Results: Daily drinkers had higher IOP compared to those who never drank (β = 0.45, 95% confidence interval (CI) = 0.05, 0.86). An increase in total weekly alcohol intake (per 5 drinks) was also associated with higher IOP (β = 0.20, 95% CI = 0.15, 0.26). The association between total alcohol intake and IOP was stronger in those with a higher genetic risk of glaucoma (P for interaction term = 0.041). There were 1525 people who reported being diagnosed with glaucoma. Alcohol consumption frequency and total alcohol intake were not associated with glaucoma. Conclusions: Alcohol frequency and total alcohol intake were associated with elevated IOP but not with glaucoma. The PRS modified the association between total alcohol intake and IOP. Findings should be confirmed in longitudinal analyses.