Date of Award

January 2026

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Mathieu Bakhoum

Abstract

Abstract:

a) Background: The eye offers a unique, non-invasive window to study early pathogenic markers, monitor chronic conditions, and diagnose occult disease. The overall objective of this investigation is to study the relationship between ocular phenotypes and vascular health.

b) Research Aims: The aims of this study are two-fold: 1. Investigating the association between retinal vascular occlusions and stroke in patients with atrial fibrillation and 2. Exploring the association between normal tension glaucoma (NTG) and vascular risk factors.

c) Hypothesis: We hypothesize that retinal vascular occlusions will continue to be associated with an increased risk of stroke in patients diagnosed with atrial fibrillation. In doing so, we hope to develop a method to further stratify patients in this high-risk population who may benefit from anticoagulation. 2. Exploring the association between normal tension glaucoma (NTG) and vascular risk factors. Our hypothesis was that NTG risk is associated primarily with systemic vascular dysfunction, while HTG aligns more closely with traditional cardiometabolic risk factors.

d) Methods: This is a retrospective, cross-sectional study utilizing retrospective data from the previously published Jayaraj et al. The study included individuals aged 30 and above, who underwent an evaluation by an ophthalmologist or optometrist as well as by a general medical practitioner at Yale University or Yale New Haven Health. Diagnostic records were obtained through the electronic medical record tool, Epic SlicerDicer, and using the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes. Multivariable logistic regression models were used to evaluate the relationship between RAO or RVO and stroke in individuals with AFIB and the relationship between NTG and HTG and vascular risk factors. Statistical analyses were conducted using R-program version 4.4.2 (Vienna, Austria) and GraphPad Prism version 10.4.0.

e) Results: Upon multivariable regression, RAO (OR: 4.60, CI: 3.36-6.35, p<0.001) and RVO (OR: 1.47, CI: 1.11-1.93, p= 0.006), were significantly associated with stroke in patients with atrial fibrillation, with RAO showing a more pronounced association. Adjusting for a modified CHA2DS2-VASc score, RAO remained significantly associated with stroke (OR, 4.80 [CI, 3.51–6.60], P<0.001). This was true for RVO as well (OR, 1.49 [CI, 1.13–1.94], P=0.004). For the glaucoma analysis, it was found that after adjusting for covariates in a multivariable logistic regression model, peripheral arterial disease remained independently associated with increased odds of NTG (OR: 1.42, 95% CI: 1.16–1.75, p= 0.001), while hypertension (OR: 1.34, 95% CI: 1.23–1.46, p < 0.001) and diabetes (OR: 1.35, 95% CI: 1.27–1.44, p < 0.001) were significantly associated with increased odds of HTG.

f) Conclusion: Our study offers compelling evidence for the relationship between vascular health and ocular phenotypes. There was a significant relationship between retinal vascular occlusions and stroke in individuals with AFIB demonstrating that RAO and RVO may provide valuable information for stroke risk stratification. Additionally, in our analysis we find that after controlling for relevant vascular and cardiometabolic risk factors, NTG remained associated with PAD, while HTG remained aligned with traditional cardiometabolic risk factors. These distinct disease profiles underscore the multifactorial nature of glaucoma pathophysiology.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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