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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 -
Nature Reviews. Disease Primers May 2021Age-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world. AMD is characterized by accumulation of extracellular... (Review)
Review
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world. AMD is characterized by accumulation of extracellular deposits, namely drusen, along with progressive degeneration of photoreceptors and adjacent tissues. AMD is a multifactorial disease encompassing a complex interplay between ageing, environmental risk factors and genetic susceptibility. Chronic inflammation, lipid deposition, oxidative stress and impaired extracellular matrix maintenance are strongly implicated in AMD pathogenesis. However, the exact interactions of pathophysiological events that culminate in drusen formation and the associated degeneration processes remain to be elucidated. Despite tremendous advances in clinical care and in unravelling pathophysiological mechanisms, the unmet medical need related to AMD remains substantial. Although there have been major breakthroughs in the treatment of exudative AMD, no efficacious treatment is yet available to prevent progressive irreversible photoreceptor degeneration, which leads to central vision loss. Compelling progress in high-resolution retinal imaging has enabled refined phenotyping of AMD in vivo. These insights, in combination with clinicopathological and genetic correlations, have underscored the heterogeneity of AMD. Hence, our current understanding promotes the view that AMD represents a disease spectrum comprising distinct phenotypes with different mechanisms of pathogenesis. Hence, tailoring therapeutics to specific phenotypes and stages may, in the future, be the key to preventing irreversible vision loss.
Topics: Aging; Blindness; Humans; Macular Degeneration; Oxidative Stress
PubMed: 33958600
DOI: 10.1038/s41572-021-00265-2 -
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 -
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 -
International Journal of Molecular... Oct 2020Age-related macular degeneration (AMD) and glaucoma are degenerative conditions of the retina and a significant cause of irreversible blindness in developed countries.... (Review)
Review
Age-related macular degeneration (AMD) and glaucoma are degenerative conditions of the retina and a significant cause of irreversible blindness in developed countries. Alzheimer's disease (AD), the most common dementia of the elderly, is often associated with AMD and glaucoma. The cardinal features of AD include extracellular accumulation of amyloid β (Aβ) and intracellular deposits of hyper-phosphorylated tau (p-tau). Neuroinflammation and brain iron dyshomeostasis accompany Aβ and p-tau deposits and, together, lead to progressive neuronal death and dementia. The accumulation of Aβ and iron in drusen, the hallmark of AMD, and Aβ and p-tau in retinal ganglion cells (RGC), the main retinal cell type implicated in glaucoma, and accompanying inflammation suggest overlapping pathology. Visual abnormalities are prominent in AD and are believed to develop before cognitive decline. Some are caused by degeneration of the visual cortex, while others are due to RGC loss or AMD-associated retinal degeneration. Here, we review recent information on Aβ, p-tau, chronic inflammation, and iron dyshomeostasis as common pathogenic mechanisms linking the three degenerative conditions, and iron chelation as a common therapeutic option for these disorders. Additionally discussed is the role of prion protein, infamous for prion disorders, in Aβ-mediated toxicity and, paradoxically, in neuroprotection.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Brain; Glaucoma; Humans; Macular Degeneration; Protein Aggregation, Pathological; Retina; Retinal Degeneration; Retinal Ganglion Cells; tau Proteins
PubMed: 33023198
DOI: 10.3390/ijms21197290 -
The British Journal of Ophthalmology Apr 2020Macular dystrophies (MDs) consist of a heterogeneous group of disorders that are characterised by bilateral symmetrical central visual loss. Advances in genetic testing... (Review)
Review
Macular dystrophies (MDs) consist of a heterogeneous group of disorders that are characterised by bilateral symmetrical central visual loss. Advances in genetic testing over the last decade have led to improved knowledge of the underlying molecular basis. The developments in high-resolution multimodal retinal imaging have also transformed our ability to make accurate and more timely diagnoses and more sensitive quantitative assessment of disease progression, and allowed the design of optimised clinical trial endpoints for novel therapeutic interventions. The aim of this review was to provide an update on MDs, including Stargardt disease, Best disease, X-linked r etinoschisis, pattern dystrophy, Sorsby fundus dystrophy and autosomal dominant drusen. It highlights the range of innovations in retinal imaging, genotype-phenotype and structure-function associations, animal models of disease and the multiple treatment strategies that are currently in clinical trial or planned in the near future, which are anticipated to lead to significant changes in the management of patients with MDs.
Topics: Diagnostic Imaging; Humans; Macular Degeneration; Molecular Biology; Therapeutics
PubMed: 31704701
DOI: 10.1136/bjophthalmol-2019-315086 -
Advances in Experimental Medicine and... 2021Age-related macular degeneration (AMD) is a degenerative disease of the human retina affecting individuals over the age of 55 years. This heterogeneous condition arises...
Age-related macular degeneration (AMD) is a degenerative disease of the human retina affecting individuals over the age of 55 years. This heterogeneous condition arises from a complex interplay between age, genetics, and environmental factors including smoking and diet. It is the leading cause of blindness in industrialized countries. Worldwide, the number of people with AMD is predicted to increase from 196 million in 2020 to 288 million by 2040. By this time, Asia is predicted to have the largest number of people with the disease. Distinct patterns of AMD prevalence and phenotype are seen between geographical areas that are not explained fully by disparities in population structures. AMD is classified into early, intermediate, and late stages. The early and intermediate stages, when visual symptoms are typically absent or mild, are characterized by macular deposits (drusen) and pigmentary abnormalities. Through risk prediction calculators, grading these features helps predict the risk of progression to late AMD. Late AMD is divided into neovascular and atrophic forms, though these can coexist. The defining lesions are macular neovascularization and geographic atrophy, respectively. At this stage, visual symptoms are often severe and irreversible, and can comprise profoundly decreased central vision in both eyes. For these reasons, the condition has major implications for individuals and society, as affected individuals may experience substantially decreased quality of life and independence. Recent advances in retinal imaging have led to the recognition of an expanded set of AMD phenotypes, including reticular pseudodrusen, nonexudative macular neovascularization, and subtypes of atrophy. These developments may lead to refinements in current classification systems.
Topics: Asia; Choroidal Neovascularization; Humans; Macular Degeneration; Middle Aged; Quality of Life; Retinal Drusen; Tomography, Optical Coherence
PubMed: 33847996
DOI: 10.1007/978-3-030-66014-7_1 -
JAMA Ophthalmology Jul 2020The morphologic changes and their pathognomonic distribution in progressing age-related macular degeneration (AMD) are not well understood. (Randomized Controlled Trial)
Randomized Controlled Trial
Characterization of Drusen and Hyperreflective Foci as Biomarkers for Disease Progression in Age-Related Macular Degeneration Using Artificial Intelligence in Optical Coherence Tomography.
IMPORTANCE
The morphologic changes and their pathognomonic distribution in progressing age-related macular degeneration (AMD) are not well understood.
OBJECTIVES
To characterize the pathognomonic distribution and time course of morphologic patterns in AMD and to quantify changes distinctive for progression to macular neovascularization (MNV) and macular atrophy (MA).
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included optical coherence tomography (OCT) volumes from study participants with early or intermediate AMD in the fellow eye in the HARBOR (A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) trial. Patients underwent imaging monthly for 2 years (July 1, 2009, to August 31, 2012) following a standardized protocol. Data analysis was performed from June 1, 2018, to January 21, 2020.
MAIN OUTCOMES AND MEASURES
To obtain topographic correspondence between patients and over time, all scans were mapped into a joint reference frame. The time of progression to MNV and MA was established, and drusen volumes and hyperreflective foci (HRF) volumes were automatically segmented in 3 dimensions using validated artificial intelligence algorithms. Topographically resolved population means of these markers were constructed by averaging quantified drusen and HRF maps in the patient subgroups.
RESULTS
Of 1097 patients enrolled in HARBOR, 518 (mean [SD] age, 78.1 [8.2] years; 309 [59.7%] female) had early or intermediate AMD in the fellow eye at baseline. During the 24-month follow-up period, 135 (26%) eyes developed MNV, 50 eyes (10%) developed MA, and 333 (64%) eyes did not progress to advanced AMD. Drusen and HRF had distinct topographic patterns. Mean drusen thickness at the fovea was 29.6 μm (95% CI, 20.2-39.0 μm) for eyes progressing to MNV, 17.2 μm (95% CI, 9.8-24.6 μm) for eyes progressing to MA, and 17.1 μm (95% CI, 12.5-21.7 μm) for eyes without disease progression. At 0.5-mm eccentricity, mean drusen thickness was 25.8 μm (95% CI, 19.1-32.5 μm) for eyes progressing to MNV, 21.7 μm (95% CI, 14.6-28.8 μm) for eyes progressing to MA, and 14.4 μm (95% CI, 11.2-17.6 μm) for eyes without disease progression. The mean HRF thickness at the foveal center was 0.072 μm (95% CI, 0-0.152 μm) for eyes progressing to MNV, 0.059 μm (95% CI, 0-0.126 μm) for eyes progressing to MA, and 0.044 μm (95% CI, 0.007-0.081) for eyes without disease progression. At 0.5-mm eccentricity, the largest mean HRF thickness was seen in eyes progressing to MA (0.227 μm; 95% CI, 0.104-0.349 μm) followed by eyes progressing to MNV (0.161 μm; 95% CI, 0.101-0.221 μm) and eyes without disease progression (0.085 μm; 95% CI, 0.058-0.112 μm).
CONCLUSIONS AND RELEVANCE
In this study, drusen and HRF represented imaging biomarkers of disease progression in AMD, demonstrating distinct topographic patterns over time that differed between eyes progressing to MNV, eyes progressing to MA, or eyes without disease progression. Automated localization and precise quantification of these factors may help to develop reliable methods of predicting future disease progression.
Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Artificial Intelligence; Disease Progression; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Intravitreal Injections; Macular Degeneration; Male; Prognosis; Ranibizumab; Retina; Retinal Drusen; Tomography, Optical Coherence
PubMed: 32379287
DOI: 10.1001/jamaophthalmol.2020.1376 -
Ophthalmology Mar 2021To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD), its subtypes, and large... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD), its subtypes, and large drusen.
DESIGN
Post hoc analysis of 2 controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2.
PARTICIPANTS
Eyes with no late AMD at baseline among AREDS participants (n = 4504) and AREDS2 participants (n = 3738) totaled 14 135 eyes. Mean age was 71.0 years (standard deviation, 6.7 years), and 56.5% of patients were women.
METHODS
Fundus photographs were collected at annual study visits and graded centrally for late AMD. Dietary intake of multiple nutrients was calculated from food frequency questionnaires.
MAIN OUTCOME MEASURES
Progression to late AMD, geographic atrophy (GA), neovascular AMD, and (separate analyses) large drusen.
RESULTS
Over median follow-up of 10.2 years, of the 14 135 eyes, 32.7% progressed to late AMD. For 9 nutrients, intake quintiles 4 or 5 (vs. 1) were associated significantly (P ≤ 0.0005) with decreased risk of late AMD: vitamin A, vitamin B6, vitamin C, folate, β-carotene, lutein and zeaxanthin, magnesium, copper, and alcohol. For 3 nutrients, quintiles 4 or 5 were associated significantly with increased risk: saturated fatty acid, monounsaturated fatty acid, and oleic acid. Similar results were observed for GA. Regarding neovascular AMD, 9 nutrients were associated nominally with decreased risk-vitamin A, vitamin B6, β-carotene, lutein and zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid, and alcohol-and 3 nutrients were associated with increased risk-saturated fatty acid, monounsaturated fatty acid, and oleic acid. In separate analyses (n = 5399 eyes of 3164 AREDS participants), 12 nutrients were associated nominally with decreased risk of large drusen.
CONCLUSIONS
Higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD. These associations are stronger for GA than for neovascular AMD. The same nutrients also tend to show protective associations against large drusen development. Strong genetic interactions exist for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. These data may justify further research into underlying mechanisms and randomized trials of supplementation.
Topics: Aged; Aged, 80 and over; Diet; Diet Surveys; Dietary Supplements; Disease Progression; Energy Intake; Female; Follow-Up Studies; Geographic Atrophy; Humans; Male; Middle Aged; Retinal Drusen; Wet Macular Degeneration
PubMed: 32858063
DOI: 10.1016/j.ophtha.2020.08.018