Overview and definition of age-related macular degeneration

Age-related macular degeneration as a leading cause of blindness among the elderly population

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness of the elderly worldwide. Based on the Global Vision Database, among the global population, the cause for blindness due to AMD in 1990 and 2010 was 5% and 7%, respectively. In the United States, the number of persons having AMD will increase by 50% to 2.95 million in 2020. AMD is a central-retina disease from early to late stage, with various severities ( Fig. 1.1 ). Earlier, it had been believed that this kind of blindness is predominantly from a rapidly progressing form, that is, neovascular or wet AMD. Currently, it is understood that the etiologies of visual impairment in AMD patients consist of both wet AMD and an advanced form of dry AMD, that is, geographic atrophy (GA). Vision loss by GA is characterized by a gradual progression, due to the subtle nature of GA growth and its poor association with vision impairment. In real life, enlarging GA lesions could be harbored for years before encroaching on the fovea, the center of the macula. Therefore, a large portion of GA progression is not easily discerned or quantified and the annual rate of vision impairment due to GA may be underestimated.

AMD is a serious gerontologic disease. Although the pathogenesis underlying this human age-related disease is not completely understood, advanced age appears to be the strongest risk factor. The evidence from epidemiological studies shows that the prevalence of AMD increases with age. In the United States, approximately one in eight people (12.5%) over the age of 60 has some degree of macular degeneration. For seniors over age 80, one in three (33%) has AMD. The number of people living with macular degeneration is expected to reach 196 million worldwide by 2020 and increase to 288 million by 2040. As a whole, the rapidly rising incidence of AMD is caused by the aging of the population worldwide. The social and economic impact of AMD is enormous.

AMD and its negative impact on quality of life

AMD involves the progressive dysfunction and degeneration of the macula’s photoreceptors that eventually lead to loss of central vision. With the increase in the aging population, AMD will become an even more common problem. As AMD incidence increases, it is important to understand how it affects the visual function and quality of life (QoL) of patients. The test of QoL is a subjective measure, using patient-reported outcome measures, normally via a questionnaire. When central scotomas extend beyond 20 degrees of diameter at the advanced stage of AMD, usually in both eyes, the profound loss of central vision leads to visual disability, including inability to drive, to read, or to recognize human faces. This severe consequence has a negative impact on the patients’ autonomy and QoL. Among central visual functions, face recognition is an important daily activity. It is agreed that peoples spend more time looking at faces than any other complex visual stimuli. Face recognition is essential to social interactions. Difficulties with face recognition can lead to embarrassment and anxiety in social situations, which in turn can lead to social isolation and depression. Based on studies from 1988 to 2002, 171 people with AMD from five cohort studies received the QoL test to evaluate the effect of AMD on face recognition. These studies collected a range of outcomes including familiar face recognition, facial expression discrimination, and eye movements when viewing an image of a face. AMD patients performed worse on categorizing facial expressions than on yes-no questions. Familiar face recognition and facial expression detection performance worsened with reduced luminance. One study reported significant differences in eye movements with AMD compared to the controls. The profound visual impairment of AMD patients such as the inability of face recognition may lead to depression. Depression is the most frequent psychiatric disorder in AMD patients (33.7%). Meanwhile, a significant association also was found between AMD and anxiety, adjustment disorders, and somatoform disorders.

AMD may also trigger the development of multiple psychiatric conditions. It has been found that patients with AMD are at greater risk for cognitive impairment than the non-AMD controls, suggesting that this ophthalmological disease is not just associated with depression and anxiety. The relationship between depression, anxiety, and AMD is complex and involves several possibilities. One hypothesis is that valued activities are impaired among AMD patients with major visual function loss, indirectly increasing the risk of developing affective suffering and distress. It is noteworthy that elderly patients with AMD are often affected by other chronic conditions. As a result, it is possible that individuals with AMD are depressed not only because of the impairment of their visual acuity but also because of the impact of their other medical conditions on their daily lives. This fact highlights the importance of interdisciplinary management of patients with AMD to prevent the development of depression and anxiety.

In the retinal clinic, wet AMD patients receiving intravitreal antivascular endothelial growth factor (VEGF) therapy often describe a physical and psychological stress. Most studies on depression associated with AMD are earlier reports, before the era of intravitreal anti-VEGF therapy, now the mainstay of treatment for wet AMD. This revolutionized therapy has significantly reduced the risk of central vision loss caused by wet AMD. This is a positive impact on vision outcomes. On the other hand, the patients need repeated intravitreal injections often for many years to maintain the anti-VEGF efficacy. This is a stressful event with anticipatory anxiety for many patients. It has been reported that the prevalence of depression and anxiety in the wet AMD patients with anti-VEGF treatment is still significantly higher than in the general population. A recent study utilizing qualitative data and validated questionnaires showed that anxiety is associated with intravitreal anti-VEGF injections. The source of anxiety is related not only to the fear of the injection, but also to concern over effectiveness of the treatment. The levels of clinical depression, not anxiety levels, are significantly higher in association with the initial three injections than with subsequent injections.