Abstract by Jens Rovelt Andreasen

The eye disease glaucoma constitutes a major global health challenge. It affects around 76 million people worldwide, and the number of patients is expected to reach 111.8 million by 2040, mainly due to the aging population. Glaucoma is defined by progressive degeneration of the optic nerve with simultaneous loss of peripheral vision. There are several subtypes of glaucoma. Primary open-angle glaucoma is the most common subtype, and the major risk factors include elevated intraocular pressure, age, and genetic predisposition. The gradual onset of primary open-angle glaucoma and the often unnoticed peripheral vision loss can progress to severe and irreversible visual impairment or blindness. Therefore, research into the risk factors of glaucoma is important as it can help identify people who are at particular risk of developing the disease. Hence, analyzing patient self-assessment measurements in relation to glaucoma can help in specifically understanding the characteristics of the disease, leading to better risk profiling, disease prevention and management.

There are several risk factors other than the most common ones mentioned above that have been associated with primary open-angle glaucoma. Research has shown that conditions such as sleep apnea, high blood pressure, and cardiovascular disease, as well as certain brain disorders and some lifestyle habits may be associated with the development of the disease. While glaucoma research has mostly focused on clinically and objectively measurable risk factors, the information contained in glaucoma patients' self-rated health and vision is largely unexplored, which could help profile glaucoma risk.

Self-rated health and vision assessment tools, which utilize 5-point scales (with 1 meaning “Excellent” and 5 meaning “Very bad”), offer comprehensive indicators of an individual's health and vision status and are widely used in research. Self-rated health has been shown to predict mortality and reflect overall body status, which is influenced by the underlying conditions and diseases present in an individual. Similarly, self-rated vision is linked to various measurements of visual function and can provide additional insights into the health of a person’s eyes. Furthermore, the impact of poorly self-rated concerns about vision has not been studied in relation to glaucoma, although worry and anxiety may indicate underlying issues that can ultimately affect one’s prognosis. Together, these three measures are well suited to provide a comprehensive picture of a person's health and give insight into underlying issues that conventional clinical tests may not capture. Analyzing these assessments in relation to glaucoma can hopefully lead to better risk profiling as well as disease prevention and management, as they summarize a person’s health and vision status.

To facilitate further the analysis of the risk factors for glaucoma, data from the research initiative Project FOREVER were used. Project FOREVER is a Danish cohort that aims to collect comprehensive eye and vision data from about 300,000 individuals, in collaboration with a leading national optical chain. These data include extensive clinical eye examinations and responses to a questionnaire that covers various topics such as lifestyle habits, eye conditions, self-rated health, and self-rated vision. Among other objectives, Project FOREVER aims to facilitate studies that can generate new knowledge about the risk factors for eye diseases in order to prevent and improve overall eye health in the population.

In this thesis, the initial aim was to gather current evidence about the risk factors for primary open-angle glaucoma through an overview of systematic reviews (Paper 1). We identified 25 risk factors where sleep apnea, diabetes, vitamin intake and Helicobacter Pylori infections were analyzed in several systematic reviews as opposed to one. The goal of Paper 1 was to provide a concise overview and serve as a guide for the choice of risk factors in subsequent evidence-based research. The results from Paper 1 showed that sleep apnea was the most significant risk factor associated with glaucoma. To confirm this finding, we used data obtained from the questionnaire distributed as part of Project FOREVER (described in Paper 2) to calculate the strength and direction of the association between sleep apnea and glaucoma (Paper 3). We found that sleep apnea was statistically significantly associated with glaucoma (odds ratio=1.48, 95% CI: 1.04 – 2.04, p=0.022), supporting previous evidence. The data in Project FOREVER further enabled association studies regarding glaucoma and self-rated vision, self-rated vision concerns, and self-rated health. In Paper 4, we showed that persons with glaucoma had significantly poorer ratings across all three measurements compared to persons without glaucoma, suggesting that patients’ self-rated vision, vision concerns, and health are effective for risk profiling and can be used accordingly.

Overall, this thesis focused on the risk factors for glaucoma, and using the extensive Project FOREVER dataset, sleep apnea, self-rated vision, self-rated vision concerns, and self-rated health were substantiated as important associations that can potentially be used to stratify risk in the population. Of course, further studies are needed to pave the way for clinically relevant algorithms that can, at best, be evaluated in the FOREVER population before implementation.