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The Medical Clinics of North America May 2021Age-related macular degeneration (AMD) is a leading cause of blindness. The main risk factor is advancing age, with the severity of vision loss ranging from mild to... (Review)
Review
Age-related macular degeneration (AMD) is a leading cause of blindness. The main risk factor is advancing age, with the severity of vision loss ranging from mild to severe. There is a 25% risk of early AMD and 8% risk of late AMD in patients over the age of 75, with the number of cases expected to increase because of the aging population. Diagnosis of the disease requires a dilated fundus examination. Physicians should be aware of the symptoms, risk factors, and treatment options for AMD to refer appropriately for ophthalmologic evaluation. Early detection can be helpful to prevent disease progression.
Topics: Blindness; Humans; Macular Degeneration; Risk Factors; Sensory Aids; Vision, Low
PubMed: 33926642
DOI: 10.1016/j.mcna.2021.01.003 -
Deutsches Arzteblatt International Jul 2020Age-related macular degeneration (AMD) is thought to cause approximately 9% of all cases of blindness worldwide. In Germany, half of all cases of blindness and... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is thought to cause approximately 9% of all cases of blindness worldwide. In Germany, half of all cases of blindness and high-grade visual impairment are due to AMD. In this review, the main risk factors, clinical manifestations, and treatments of this disease are presented.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed for original articles and reviews, as well as on current position statements by the relevant specialty societies.
RESULTS
AMD is subdivided into early, intermediate, and late stages. The early stage is often asymptomatic; patients in the other two stages often have distorted vision or central visual field defects. The main risk factors are age, genetic predisposition, and nicotine consumption. The number of persons with early AMD in Germany rose from 5.7 million in 2002 to ca. 7 million in 2017. Late AMD is subdivided into the dry late form of the disease, for which there is no treatment at present, and the exudative late form, which can be treated with the intravitreal injection of VEGF inhibitors.
CONCLUSION
More research is needed on the dry late form of AMD in particular, which is currently untreatable. The treatment of the exudative late form with VEGF inhibitors is labor-intensive and requires a close collaboration of the patient, the ophthalmologist, and the primary care physician.
Topics: Germany; Humans; Intravitreal Injections; Macular Degeneration; Risk Factors
PubMed: 33087239
DOI: 10.3238/arztebl.2020.0513 -
Ophthalmologica. Journal International... 2021Among older adults, age-related macular degeneration (AMD) is a prevalent disabling condition that begins as subtle visual disturbances and can progress to permanent... (Review)
Review
Among older adults, age-related macular degeneration (AMD) is a prevalent disabling condition that begins as subtle visual disturbances and can progress to permanent loss of central vision. In its late neovascular form, AMD is treatable with inhibitors of vascular endothelial growth factor, the key driver of exudative disease. In the atrophic form, treatment remains elusive. This review addresses the natural history of AMD - through early, intermediate, and advanced disease stages - and concentrates on diagnosis and risk stratification, deficiencies of current treatments, and the promising findings of emerging therapies.
Topics: Aged; Blindness; Humans; Macular Degeneration; Vascular Endothelial Growth Factor A
PubMed: 34130290
DOI: 10.1159/000517520 -
Cells Sep 2021Aging contributes to the risk of development of ocular diseases including, but not limited to, Age-related Macular Degeneration (AMD) that is a leading cause of... (Review)
Review
Aging contributes to the risk of development of ocular diseases including, but not limited to, Age-related Macular Degeneration (AMD) that is a leading cause of blindness in the United States as well as worldwide. Retinal aging, that contributes to AMD pathogenesis, is characterized by accumulation of drusen deposits, alteration in the composition of Bruch's membrane and extracellular matrix, vascular inflammation and dysregulation, mitochondrial dysfunction, and accumulation of reactive oxygen species (ROS), and subsequent retinal pigment epithelium (RPE) cell senescence. Since there are limited options available for the prophylaxis and treatment of AMD, new therapeutic interventions are constantly being looked into to identify new therapeutic targets for AMD. This review article discusses the potential candidates for AMD therapy and their known mechanisms of cytoprotection in AMD. These target therapeutic candidates include APE/REF-1, MRZ-99030, Ciliary NeuroTrophic Factor (CNTF), RAP1 GTPase, Celecoxib, and SS-31/Elamipretide.
Topics: Angiogenesis Inhibitors; Animals; Humans; Macular Degeneration; Molecular Targeted Therapy
PubMed: 34572131
DOI: 10.3390/cells10092483 -
Cellular and Molecular Life Sciences :... May 2021Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly... (Review)
Review
Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.
Topics: Aging; Animals; Complement Activation; Complement System Proteins; Genetic Predisposition to Disease; Humans; Inflammation; Macular Degeneration; Oxidative Stress; Risk Factors
PubMed: 33751148
DOI: 10.1007/s00018-021-03796-9 -
Progress in Retinal and Eye Research Nov 2020Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells... (Review)
Review
Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. The ubiquitin-proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is increasing evidence that proteostasis is disturbed in RPE as evidenced by lysosomal lipofuscin and extracellular drusen accumulation in AMD. Nuclear factor-erythroid 2-related factor-2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) are master transcription factors in the regulation of antioxidant enzymes, clearance systems, and biogenesis of mitochondria. The precise cause of RPE degeneration and the onset and progression of AMD are not fully understood. However, mitochondria dysfunction, increased reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage are observed together with increased protein aggregation and inflammation in AMD. In contrast, functional mitochondria prevent RPE cells damage and suppress inflammation. Here, we will discuss the role of mitochondria in RPE degeneration and AMD pathology focused on mtDNA damage and repair, autophagy/mitophagy signaling, and regulation of inflammation. Mitochondria are putative therapeutic targets to prevent or treat AMD.
Topics: Autophagy; Humans; Lysosomes; Macular Degeneration; Mitochondria; Oxidative Stress; Retinal Pigment Epithelium; Signal Transduction
PubMed: 32298788
DOI: 10.1016/j.preteyeres.2020.100858 -
Eye (London, England) Feb 2022Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as... (Review)
Review
Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.
Topics: Genetic Therapy; Geographic Atrophy; Humans; Macular Degeneration
PubMed: 35017696
DOI: 10.1038/s41433-021-01842-1 -
The New England Journal of Medicine Aug 2021A 78-year-old woman presents with vision changes in the right eye for one week. Specifically, she describes central blurring in her vision and bending or waviness in... (Review)
Review
A 78-year-old woman presents with vision changes in the right eye for one week. Specifically, she describes central blurring in her vision and bending or waviness in straight lines. She also reports increasing difficulty reading print and often feels that there are blind spots in her vision. How would you diagnose and treat this patient?
Topics: Aged; Dietary Supplements; Female; Humans; Macular Degeneration; Patient Education as Topic; Practice Guidelines as Topic; Retina; Retinal Drusen; Severity of Illness Index; Slit Lamp Microscopy; Vascular Endothelial Growth Factor A
PubMed: 34347954
DOI: 10.1056/NEJMcp2102061 -
Lutein and Zeaxanthin and Their Roles in Age-Related Macular Degeneration-Neurodegenerative Disease.Nutrients Feb 2022Lutein and zeaxanthin belong to the xanthophyll family of carotenoids, which are pigments produced by plants. Structurally, they are very similar, differing only... (Review)
Review
Lutein and zeaxanthin belong to the xanthophyll family of carotenoids, which are pigments produced by plants. Structurally, they are very similar, differing only slightly in the arrangement of atoms. Key sources of these carotenoids include kale, savoy cabbage, spinach, broccoli, peas, parsley, corn, and egg yolks. The recommended daily intake of lutein is approximately 10.0 mg and that of zeaxanthin is 2 mg. Lutein intake in adults varies, with average intakes being 1-2 mg/day. Due to the lack of synthesis of consumption of these compounds in humans, these substances are extremely important for the proper functioning of certain organs of the body (eye, skin, heart, intestines). Eating a lot of dark leafy vegetables and some fruits can help to prevent our bodies from developing diseases. The protective effects of carotenoids are mainly related to their defense against oxidative stress and their ability to scavenge free radicals. Lutein and zeaxanthin are the only dietary carotenoids that accumulate in the retina, specifically the macula, and are called macular pigments. These carotenoids are concentrated by the action of specific binding proteins such as StARD3, which binds lutein, and GSTP1, which binds zeaxanthin and its dietary metabolite, mesozeaxanthin. It has been shown that supportive therapy with lutein and zeaxanthin can have a beneficial effect in delaying the progression of eye diseases such as age-related macular degeneration (AMD) and cataracts. This article presents the current state of knowledge on the role of lutein and zeaxanthin, especially from human studies targeting their metabolism and bioavailability, with recommendations to consume xanthophyll-rich foods.
Topics: Adult; Humans; Lutein; Macular Degeneration; Macular Pigment; Neurodegenerative Diseases; Zeaxanthins
PubMed: 35215476
DOI: 10.3390/nu14040827 -
Ophthalmology Apr 2021The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study).
DESIGN
International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial.
PARTICIPANTS
A total of 286 participants with GA secondary to AMD.
MAIN OUTCOME MEASURES
The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at 3 timepoints: baseline, month 6, and month 12.
RESULTS
The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (P = 0.0051) for the avacincaptad pegol 4 mg cohort compared with their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol-related adverse events (AEs) or inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of endophthalmitis. The most frequent ocular AEs were related to the injection procedure.
CONCLUSIONS
Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. Because C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
Topics: Aged; Aged, 80 and over; Aptamers, Nucleotide; Complement C5; Complement Inactivating Agents; Double-Blind Method; Female; Fluorescein Angiography; Follow-Up Studies; Geographic Atrophy; Humans; Intravitreal Injections; Macular Degeneration; Male; Prospective Studies; Visual Acuity
PubMed: 32882310
DOI: 10.1016/j.ophtha.2020.08.027