Age-relatedMacular Degeneration Beyond the Age-related Eye Disease Study II

November 2016

Stuart Richer, OD, MS, PhD, Lawrence Ulanski II, MD, Natalia A Popenko, MS, MD Candidate, Steven G. Pratt, MD, ABIHM, Dorothy Hitchmoth, OD, ABO, ABCMO, Paul Chous, MA, OD, Shana Patel, MS, MD Candidatec, Shivani Sockanathan, MS, MD Candidatec, Bill Sardi, BS

Introduction

Pharmacologic breakthroughs abound for treating acute neovascular age-related macular degeneration (AMD). However, for most patients with atrophic (dry) AMD, or when exudative (wet) AMD is treated with intravitreous anti–vascular endothelial growth factor (VEGF) agents, there is a common experience. That theme is a relentless progressive destruction of the photoreceptor Bruch membrane–retinal pigment epithelium (RPE) complex and neural retina with age. A plethora of emerging investigational, atrophic AMD agents address the compartmental processes of visual cycle modulation, neural growth/viability, inflammation, amyloid accumulation, alternative complement, antioxidants, and stem cells. However, AMD remains, at its essence, a chronic multifactorial disease of aging, under the influence of genes activated by supportive as well as
destructive environmental influences.

Underlying retinal health, the supportive vascular choroidal bed thins with age, and much faster in patients with glaucoma or AMD. Oculovascular disease is activated by several repeated and prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic factors causing a protracted host defense response with consequent vascular damage [1]. Protection of peripheral endothelial end-organ capillary beds like the choriocapillaris should encompass more than a hurried discussion on smoking cessation. Besides smoking reduction/cessation and reducing endothelial damage from chronic inflammation, an extended doctor-patient dialogue is needed concerning
the importance of cardiovascular physical fitness, reduction of abdominal adiposity (nonalcoholic fatty liver disease [NAFLD]), minimizing glycemic load (with its promotion of insulin resistance), stress reduction (supporting the hypothalamic-pituitary-adrenal axis), microbiome and digestive competence, vascular nitric oxide stimulation (for greater blood flow), and caloric restriction (CR) (fasting or mimicry through the use of metformin and/or resveratrol [RV]).

Individual differences also matter. A dozen physiologic biomarkers, assessed comprehensively in 1000 subjects, can vary by a factor of 3 even in asymptomatic young adults between 28 and 38 years old [2]. Approximately 4% of a European cohort of patients with AMD acquired AMD before age 45 years. Environmental factors, including nutrient intake, are modifiable, affecting an individual’s rate of aging, despite the inherited DNA genetic profile. There are 8 nongenetic factors (age, alcohol use, allergies, education, sunlight exposure, fish consumption, physical exercise, and mineral overload) that provide equivalent discrimination between AMD and no AMD comparable with existing DNA single-nucleotide polymorphism (SNP) risk models [3].

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