Overview of Age-Related Ocular Conditions

Published Online: May 26, 2013
Esen K. Akpek, MD; and Roderick A. Smith, MS
The United States is an aging society. The number of Americans 65 years or older is expected to more than double over the next 40 years, from 40.2 million in 2010 to 88.5 million in 2050, with aging baby boomers accounting for most of the increase. As the society ages, the prevalence of age-related diseases, including diseases of the eye, will continue to increase. By 2020, age-related macular degeneration, one of the leading causes of vision loss, is expected to affect 2.95 million individuals in the United States. Likewise, the prevalence of open-angle glaucoma, estimated at 2.2 million in 2000, is projected to increase by 50%, to 3.36 million by 2020. As the eye ages, it undergoes a number of physiologic changes that may increase susceptibility to disease. Environmental and genetic factors are also major contributors to the development of age-related ocular diseases. This article reviews the physiology of the aging eye and the epidemiology and pathophysiology of 4 major age-related ocular diseases: age-related macular degeneration, glaucoma, diabetic retinopathy, and dry eye.

(Am J Manag Care. 2013;19:S67-S75)
The population of the United States continues to age, a trend consistent with many western industrialized nations and some Asian societies. According to the US Census Bureau, the number of Americans 65 years or older is expected to increase from 40.2 million in 2010 to 88.5 million in 2050, with most of the increase attributable to aging baby boomers.1 Nearly 1 in 5 US residents will be above age 65 years by 2030, the time at which all of the baby boomers will represent the country’s older population.1 The number of oldest Americans (≥85 years of age) is projected to increase from 5.8 million in 2010 to 8.7 million in 2030, and to approximately 19 million in 2050, when they will account for 4.3% of the population.1 Figure 1 shows the projected changes in the age distribution of older Americans in the coming decades.

Consistent with this trend, the prevalence of age-related conditions is also rapidly increasing. As the body ages, changes in the structural and functional characteristics of the vasculature combined with behavioral, genetic, and environmental risk factors contribute to the development of age-related vascular diseases, such as atherosclerosis, renal insufficiency, and cerebrovascular disease.2 Advancing age remains the strongest independent risk factor for developing atherosclerotic cardiovascular disease.2 Advanced age is a major risk factor for many eye diseases. The incidence and prevalence of age-related macular degeneration (AMD), glaucoma, and vascular occlusive diseases increase significantly with age.2 Among US adults, the prevalence of glaucoma is 0.7% among those aged 40 to 49 years and 1.8% among those aged 60 to 69 years, and increases to 7.7% for those 80 years and older.3 Similarly, the prevalence of AMD increases from 2.1% in the 40 to 49 year age group to 35.4% among individuals aged 80 years and above.3

The frequency of visual impairment associated with ocular diseases of aging is increasing rapidly. According to the Eye Disease Prevalence Research Group (EDPRG), in 2000, an estimated 937,000 Americans (0.78%) over age 40 years were blind, as defined by a best-corrected visual acuity of 20/200 or worse in the better-seeing eye, and an additional 2.4 million individuals (1.98%) had low vision, defined as best-corrected visual acuity less than 20/40, which is the level of vision required for driving.4

The EDPRG projected that the number of blind persons living in the United States will increase to 1.6 million (1.1%) by 2020, and the number living with low vision to 3.9 million (2.5%), for a total of 5.5 million visually impaired Americans (3.6% of the total population). Much of this increase is attributable to the demographics of an aging population—while persons aged 80 years and older comprised only 7.7% of the population in 2000, they accounted for almost 70% of observed blindness.

Predictably, the dramatic increase in the prevalence of vision impairment among older Americans will have enormous societal and economic implications. The estimated total financial costs of major vision disorders in the United States in 2004 was $35.4 billion—$16.2 billion in direct medical costs, $11.1 billion in other direct costs, and $8 billion in lost productivity.5 A 2010 study by the AMD Alliance International put the worldwide cost of vision loss at an estimated $3 trillion; of that amount, visual impairment due to AMD alone accounted for $343 billion, including $255 billion in direct healthcare costs.6

The past decade has seen significant advances in the treatment of several of the most common ocular diseases associated with advancing age. For example, the introduction of anti-vascular endothelial growth factor (anti-VEGF) agents has revolutionized treatment of the neovascular, or wet, form of AMD.7 These drugs are now being applied to other exudative ocular conditions, including diabetic macular edema (DME) and branch and central retinal vein occlusions.7 The success of these new therapies comes at a high price, however—a single intravitreal injection of the VEGF inhibitor ranibizumab costs approximately $2000.8

This article reviews the basic physiological changes in the aging eye that set the stage for development of ocular disease and provides an overview of the epidemiology and pathophysiology of 4 major age-related eye conditions: AMD, glaucoma, diabetic retinopathy (DR), and dry eye disease.

Physiological Changes in the Aging Eye

As the eye ages, it undergoes a number of structural and functional changes that increase susceptibility to ocular diseases. These changes include loss of cells in the ganglion layer, loss of retinal pigment epithelial cells and photoreceptors, changes to the optic nerve, reduced blood flow, condensation of the vitreous gel, loss of endothelial cells, and meibomian gland dysfunction.2,9,10

Thickness of the retinal nerve fiber layer decreases by an average of 3 μm per decade, corresponding to a loss of approximately 60,000 retinal ganglion cells.11 On average, the retina of a 95-year-old contains approximately half as many retinal ganglion cells as that of a 25-year-old.11 Changes that occur with age to the retinal pigment epithelium (RPE) are central to the development of AMD. One of the essential functions of the RPE is renewal of photoreceptors through phagocytosis of metabolic byproducts and cellular debris.12 As the number of retinal pigment epithelial cells declines with age, phototoxic waste products and debris, such as lipofuscin, A2E, and chromophores, accumulate in the RPE.12 It is estimated that these debris can occupy one-fifth of the total volume in an RPE cell in the eyes of an 80-year-old individual.12 These substances damage cell membranes and deoxyribonucleic acid, and induce chronic inflammation, which can lead to AMD (Figure 2).12

Age-related vascular changes that occur systemically also affect ocular vascular beds. Studies show that ocular blood flow generally diminishes with age, which may result from an atherosclerotic process and narrowing of the retinal vessels.2 There is a progressive thinning of the choroid, the vascular membrane that lies between the retina and the sclera, from 193 μm in the first decade of life to 84 μm in the tenth decade.13 Choriocapillary density decreases by 45%—from 0.75 in the first decade to 0.41 in the tenth decade—and lumen diameter of the choriocapillaris decreases by 34%.14 Vascular changes in the eye are thought to impede regulation of blood pressure and flow, limiting the exchange of nutrients and removal of metabolic waste and creating conditions of ischemia.2

Dysfunction of the vascular endothelium, a monolayer of cells covering the inner surface of blood vessels, is a common pathological feature of a number of age-related diseases and is thought to be a factor in some ocular diseases, such as glaucoma.2 The vascular endothelium regulates the microcirculation through the release of vasoactive factors, including the vasodilator nitric oxide (NO) and the vasoconstrictor endothelin-1.2 In the aging eye, endothelial dysfunction leads to decreased production of NO, thereby increasing vascular tone and vasoconstriction, and restricting blood flow.2 Reduced NO levels have been reported in the aqueous humor of patients with glaucoma, suggesting that vascular endothelial dysfunction plays a role in the pathophysiology of this condition.2

With advanced age, changes also affect the ocular surface. Structural and functional changes to the cornea that occur with age can affect its ability to refract light and repair itself, and can leave it more vulnerable to infection.9 As the cornea ages, there is an increase in epithelial permeability, which may represent a breakdown of epithelial barrier function.9 Moreover, there is a gradual decrease in the number of corneal endothelial cells with age that may adversely affect endothelial function and leave the cornea more vulnerable to hypoxic stress.9 Aging is also a major risk factor for dysfunction of the meibomian gland, a specialized sebaceous gland located in the eyelid that releases a mixture of lipids that lubricate the surface of the eye and prevents tear evaporation.10 Consequences of meibomian gland dysfunction (MGD) include increased tear evaporation, tear film instability, increased shear stress, and inflammation of the ocular surface—all of which are major clinical features of dry eye disease.10

Age-Related Macular Degeneration

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