Age-Related Macular Degeneration

Abstract

ImportanceAge-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040.ObservationsOlder age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment.Conclusions and RelevanceThe prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

Cellular ROS and Antioxidants: Physiological and Pathological Role

“…Antioxidants such as lutein, zeaxanthin [37], and vitamin C [38] have been shown to confer significant benefits to ocular health, contributing to maintaining healthy eyes. These antioxidants play crucial roles in preventing oxidative stress within ocular tissues, thereby helping to preserve visual function and protect against age-related degenerative changes and cataracts [39].…”

Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration

“…AMD appears to be a complex condition and consists of numerous processes and mechanisms, including various non-modifiable risk factors, such as age, female gender, white race, and genetic background, which affect its development and progression [6][7][8]. Over 30 identified genes are linked to a higher risk of AMD development.…”

“…However, the strongest genetic risk variant for AMD is thought to be polymorphism of the complement factor H gene (Y402H) [9][10][11]. Modifiable risk factors include the following: cigarette smoking, cardiovascular diseases, high serum lipid levels, abdominal obesity, a diet with a low intake of antioxidants, and exposure to ultraviolet radiation, as well as local factors such as cataract surgery and blue irises [6,7,[12][13][14][15].…”

Fas Ligand enhances vessel maturation and inhibits vascular leakage associated with age-related macular degeneration

“…The formation of these immature choroidal neovessels results in leakage of fluid and blood cells causing retinal edema and the ensuing death of photoreceptors. The current anti-vascular endothelial growth factor (VEGF) antibody therapy for neovascular AMD has been quite successful at preventing vascular leakage, resolving retinal edema, and preventing vision loss [3,4]. However, this treatment requires long-term inhibition of VEGF by repeated intravitreal injections of anti-VEGF antibody, and if treatment is discontinued disease progression resumes.…”