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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 -
Romanian Journal of Ophthalmology 2015The objective of our study was to review the current knowledge on Age- Related Macular Degeneration, including pathogenesis, ocular manifestations, diagnosis and... (Review)
Review
OBJECTIVES
The objective of our study was to review the current knowledge on Age- Related Macular Degeneration, including pathogenesis, ocular manifestations, diagnosis and ancillary testing.
SYSTEMATIC REVIEW METHODOLOGY
Relevant publications on Age-Related Macular Degeneration that were published until 2014.
CONCLUSIONS
Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterized by the appearance of drusen in the macula, accompanied by choroidal neovascularization (CNV) or geographic atrophy.
Topics: Aged; Aging; Diagnosis, Differential; Disease Progression; Fluorescein Angiography; Geographic Atrophy; Humans; Macular Degeneration; Prevalence; Retinal Drusen; Risk Factors; Romania; Tomography, Optical Coherence; Wet Macular Degeneration
PubMed: 26978865
DOI: No ID Found -
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 -
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 -
International Journal of Molecular... Jan 2021Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by... (Review)
Review
Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD's progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.
Topics: Animals; Biomarkers; Clinical Trials as Topic; Disease Management; Disease Susceptibility; Humans; Inflammasomes; Macular Degeneration; Molecular Targeted Therapy; NLR Family, Pyrin Domain-Containing 3 Protein; Prevalence; Retinal Neovascularization; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33504013
DOI: 10.3390/ijms22031170 -
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 -
Ophthalmology Mar 2018Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic... (Review)
Review
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm/year (median, ∼1.78 mm/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.
Topics: Disease Progression; Fluorescein Angiography; Fundus Oculi; Geographic Atrophy; Humans; Macular Degeneration; Retinal Pigment Epithelium; Visual Acuity
PubMed: 29110945
DOI: 10.1016/j.ophtha.2017.08.038