Abstract: To describe the current aging population in China and globally, especially as it applies to age-related macular degeneration (AMD). To review the current standards of care for treating both wet (exudative) eAMD and dry (atrophic) aAMD. And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study (AREDS) using eye bank tissue. A literature search that outlines current aging populations, standards of clinical treatment as defined by large, multicenter, randomized clinical trials that present level-I data with a low risk for bias. An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes. Analysis includes proteomic, cellular, and functional genomics. The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth (anti-VEGF) agents alone or in combination with photodynamic therapy. Monotherapy treatment intervals may be monthly, as needed, or by using a treat-and-extend (TAE) protocol. There are no proven therapies for aAMD. AMD that is phenotypically defined at AREDS level 3, should be managed with the use of anti-oxidant vitamins, lutein/zeaxanthin and zinc (AREDS-2 formulation). By understanding the multiple etiologies in the pathogenesis of AMD (i.e., oxidative stress, inflammation, and genetics), the use of human eye bank tissues graded according to the Minnesota Grading System (MGS) will enable future insights into the pathogenesis of AMD. Initial AMD management is with lifestyle modification such as avoiding smoking, eating a healthy diet and using appropriate vitamin supplements (AREDS-2). For eAMD, anti-VEGF therapies using either pro re nata (PRN) or TAE protocols are recommended, with photodynamic therapy in appropriate cases. New cellular information will direct future, potential therapies and these will originate from experimental models, such as the proposed eye bank model using the MGS, that leverages the prospective AREDS database.
Abstract: Age-related macular degeneration (AMD) remains a leading cause of severe visual impairment in developing countries. Although dry-type AMD and geographic atrophy (GA) are progressive conditions with the associated decrease of visual functions, no well-established treatment regimen was proposed for the disease. Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents, but frequent injections are a major issue for the affected patients. Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD, but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence. Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices. Simultaneously, gene therapy for dry and wet AMD is widely studied. Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease, many challenges exist in the way of its broad impact on the ocular health of AMD patients.
Abstract: Statins are used widely to treat hypercholesterolemia and atherosclerotic cardiovascular disease. They have inflammatory and immunomodulatory effects potentially useful for managing systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis. Statins also have anti-oxidative and large-vessel endothelial supportive properties that occur independent of their lipid-lowering effects. Additionally, statins can suppress macrophage and microglial activation responsible for initiating inflammatory cytokine release. More than forty percent of adults aged 65 years or older use statins in the United States and Australia, a prevalence that increases with age. The effects of statin usage on ophthalmic practice are probably underrecognized. Cardiovascular disease and age-related macular degeneration (AMD) share common risk factors, consistent with the “vascular model” of AMD pathogenesis that implicates impaired choroidal circulation in Bruch’s membrane lipoprotein accumulation. AMD has a complex multifactorial pathogenesis involving oxidative stress, choroidal vascular dysfunction, dysregulated complement-cascade-mediated inflammation and pro-inflammatory and pro-angiogenic growth factors. Many of these components are hypothetically amenable to the primary (cholesterol lowering) and secondary (anti-inflammatory, anti-oxidative, anti-vasculopathy) effects of statin use. Experimental studies have been promising, epidemiological trails have produced conflicting results and three prospective clinical trials have been inconclusive at demonstrating the value of statin therapy for delaying or preventing AMD. Cumulative evidence to date has failed to prove conclusively that statins are beneficial for preventing or treating AMD.
Abstract: Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration (AMD). Currently, aside from micronutrient supplements, there are no proven treatments for non-neovascular or dry AMD. Recently, a number of pharmacological agents have been evaluated or are under evaluation for treatment of patients with end-stage dry AMD manifesting as geographic atrophy (GA). It may preferable, however, to intervene earlier in the disease before the development of irreversible loss of visual function. Earlier intervention would require a more precise understanding of biomarkers which may increase the risk of progression from early and intermediate stages to the late stage of the disease. The development of optical coherence tomography angiography (OCTA) has allowed the layers of the retinal microcirculation and choriocapillaris (CC) to be visualized and quantified. Flow deficits in the CC have been observed to increase with age, particularly centrally, and these flow deficits appear to worsen with development and progression of AMD. As such, OCTA-based CC assessment appears to be a valuable new biomarker in our assessment and risk-stratification of AMD. Alterations in the CC may also provide new insights into the pathophysiology of the disease. Enhancement of choriocapillaris function may also prove to be a target of future therapeutic strategies or as a biomarker to monitor the effectiveness of therapy. As such, CC imaging may be anticipated to be an integral tool in the management of dry AMD.
Abstract: The most prominent causes of loss of vision in individuals over 50 years include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). While it is important to screen for these diseases effectively, current eye care is not properly doing so for much of the population, resulting in unfortunate visual disability and high costs for patients. Innovative functional testing can be unified with other screening methods for a more robust and safer screening and prediction of disease. The goal in the creation of functional testing modalities is to develop highly sensitive screening tests that are easy to use, accessible to all users, and inexpensive. The tests herein are deployed on an iPad with easily understood and intuitive instructions for rapid, streamlined, and automatic administration. These testing modalities could become highly sensitive screenings for early detection of potentially blinding diseases. The applications from our collaborators at AMA Optics include a cone photostress recovery test for detection of AMD and diabetic macular edema (DME), brightness balance perception for optic nerve dysfunction and especially glaucoma, color vision testing which is a broad screening tool, and visual acuity test. Machine learning with the combined structural and functional data will optimize identification of disease and prediction of outcomes. Here, we review and assess various tests of visual function that are easily administered on a tablet for screening in primary care. These user-friendly and simple screening tests allow patients to be identified in the early stages of disease for referral to specialists, proper assessment and treatment.
