The Relationship of Menopause to the Onset of Glaucoma in Veterans

Glaucoma is the leading cause of irreversible blindness and is projected to affect 112 million people worldwide by 2040. Unfortunately, Veterans have a 2-fold higher prevalence of developing glaucoma compared to the general US population. While the exact cause of glaucoma is unknown, recent evidence has shown that early

menopause, mutations in estrogen receptors, and polymorphism mutations along the estrogen metabolic pathway are linked to developing glaucoma. These data highlight that menopause, and particularly estrogen, may play a role in the development of this disease. However, there is a gap in our knowledge of quantifying if

menopause, regardless of age, is related to the onset of glaucoma. It is vital to understand this relationship, as 59% of the glaucomatous population are women and the number of female Veterans has doubled over the last ten years. In addition, nearly 43% of female Veterans are younger than 45-years old and will experience

menopause (average age at 51-years) within the next decade. The evidence of 1) a higher prevalence of glaucoma in Veterans, 2) the increasing number of female Veterans, and 3) the aging of female Veterans will make glaucoma a major health issue in the future for this population. The VA formed the Women’s Veterans

Health Research Network (WVHRN) to help focus attention on research and treatments for this portion of the Veteran population, and this proposal aims to understand the association between menopause, a major life event for women, and glaucoma. In this proposal, we hypothesize that menopause is related to the onset of glaucoma and will use the power

of the national VA database to perform a retrospective study to address this hypothesis. We will examine medical records from female U.S. Veterans in the corporate data warehouse (VINCI – VA Informatics and Computing Infrastructure) between 2000-2019. Previous studies summarized the impact of age of menopause on

developing glaucoma in the general population. However, this has not been confirmed in the Veteran population where glaucoma is more prevalent. In addition, no study has directly assessed whether there is a direct relationship between menopause and the onset of glaucoma. The VA database is a unique resource that can

provide longitudinal care records of patients that will allow us to understand the relationship between the onset of menopause and glaucoma and the overall incidence of glaucoma in female and male Veterans. Although glaucoma can occur at any level of intraocular pressure (IOP), elevated IOP remains clinically relevant

as a major causal risk factor for developing this disease. Several studies have shown that postmenopausal women taking hormone replacement therapy (HRT) containing estrogen had a lower IOP compared to postmenopausal women not taking HRT. This has led researchers to suggest that estrogen-based therapies

may be a potential treatment for glaucoma. Based on our work and others, we hypothesize that hormone replacement therapy containing estrogen delays the onset of developing glaucoma in postmenopausal women. This would provide evidence that estrogen is beneficial in protecting against the onset of glaucoma and

potentially lead to the development of estrogen-based treatments. To address our hypotheses and research objectives, we have assembled a team consisting of Dr. Feola, who has expertise in women’s health, menopause, and glaucoma, and a biostatistician in his laboratory. We also will have guidance and input from a VA biostatistician (Dr. Cui) and an ophthalmologist (Dr. Giangiacomo). Our

proposal will evaluate the impact of menopause and HRT on developing glaucoma in female Veterans. Our goal is to understand these relationships and communicate our findings with ophthalmology and the VA. Lastly, if successful, our future studies aim to perform more prospective studies using the Technology-based Eye Care

Services (TECS) framework to screen female patients based on glaucoma and menopause status.