Age-related eye disease and gender

Highlights

• Of the 285 million people worldwide suffering from severe visual impairment and blindness, 65% of the visually impaired and 82% of the blind people are 50 years or older.

• In all regions of the world women are in majority among the blind and visually impaired, even when adjusting for age.

• Cataract is the major cause of blindess globally and the second most common cause of visual impairment.

• Gender inequity in access to cataract surgery is a major reason for the female predominance among the blind and visually impaired.

Abstract

Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease.

Introduction

In the aging population, age-related cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are prevalent in high numbers, with about 37%, 10%, 3%, and 2% of people 70–74 years old suffering from these conditions [1]. Even though the female to male ratio varies among these eye diseases, women are in majority among the blind and the visually impaired; about two of three blind people are women [2]. This gender difference may in part be explained by the longevity of women. Other causes however, such as differences in requirement for good vision in daily life activities, in the propensity to seek health care or gender inequity in access to health care, may also contribute to this discrepancy. In addition, life-style related factors, such as smoking and sun exposure, may differ between genders and thus influence the risk of eye diseases and its distribution between sexes. Lastly, there are sex-dependent biologic differences, which may affect the disease-causing pathogenic mechanisms.

In all parts of the world and at all time periods for which data exist, the longevity pattern is the same; women live longer than men. In average, life expectancy for women is 5 years longer than for men [3]. Even though this difference is smaller in countries with high pediatric mortality and more pronounced in countries with a high overall longevity, women outlive men everywhere regardless of educational, economic, political and health critera [3]. Men have higher mortality rates than women for all the common death causes, including accidents, cardio- and cerebrovascular disorders, cancers, infections and chronic pulmonary disease [4]. Possible biologic explanations for gender-related differences in mortality and morbidity basically fall into two categories; genetical or hormonal. Genetic factors that favor female longevity are 1. the heterogametic sex hypothesis; 2. telomere attrition; and 3. mitochondrial inheritance. The importance of sexual hormones in aging is central in the reproductive theory of aging, according to which a dysfunctional hypothalmic-pituitary-gonodal (HPG) axis is associated with increased mortality in both sexes [5]. The longer life-span in women, which is even more pronounced in those entering menopause at higher age, and the fact that castrated men have the same life expectancy as women suggest that estrogens are beneficial in the aging process [6]. It is known that the risk of cardiovascular disease increases with high androgen levels and low estrogen levels both in men and in postmenopausal women [7]. Compared to premenopausal women, men have a higher prevalence of hypertension and a higher risk of cardiovascular disease. However, after menopause there is no gender difference in risk of cardiovascular disease and women even have a higher prevalence of hypertension than men of the same age [8]. A summary of genetical and hormonal effects that may promote female longevity and health is shown in Table 1. For details on the listed mechanisms, see reviews by Austad and Zetterberg [4], [9].

This review will focus on the four most common eye diseases in elderly people; age-related cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. Gender-specific prevalences and possible mechanisms for any gender differences, as well as the effect of endogenous and/or exogenous estrogen, will be presented. Knowledge on sex-related effects on pathogenic mechanisms is important to understand the basis of disease and thus provide means for new therapies. Also, finding socioeconomic explanations to gender differences in disease prevalence, such as gender inequity in access to cataract surgery, is crucial for equal allocation of health care resources (Table 2).