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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 -
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 -
Pharmacological Reports : PR 2006Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the elderly population. Its pathogenesis, likely multifactorial,... (Review)
Review
Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the elderly population. Its pathogenesis, likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors, remains poorly understood. For these reasons currently used therapeutic approaches are insufficiently effective. Although major abnormalities are seen in four functionally interrelated tissues, i.e., photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaries, the impairment of RPE cell functions is an early and crucial event in the molecular pathways leading to clinically relevant AMD changes. RPE progressively degenerate, which results in a progressive irreversible degeneration of photoreceptors. Four processes: lipofuscinogenesis, drusogenesis, inflammation and neovascularization, specifically contribute to the development of two forms of AMD, the dry form (non-exudative; geographic atrophy) and the wet form (exudative, neovascular). This paper briefly describes major molecular and cellular events leading to AMD, and presents currently used and new experimental, forthcoming therapeutic strategies.
Topics: Angiogenesis Inhibitors; Antioxidants; Choroidal Neovascularization; Genetic Predisposition to Disease; Humans; Laser Coagulation; Lipofuscin; Macular Degeneration; Photochemotherapy; Pigment Epithelium of Eye; Retinal Drusen
PubMed: 16845209
DOI: No ID Found -
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 -
Archives of Ophthalmology (Chicago,... Oct 2001Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8.
BACKGROUND
Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.
OBJECTIVE
To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.
DESIGN
The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo.
MAIN OUTCOME MEASURES
(1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.
RESULTS
Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.
CONCLUSIONS
Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.
Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Disease Progression; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Macular Degeneration; Male; Middle Aged; Prospective Studies; Risk Factors; Vision Disorders; Visual Acuity; Vitamin E; Zinc; beta Carotene
PubMed: 11594942
DOI: 10.1001/archopht.119.10.1417 -
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 -
Retina (Philadelphia, Pa.) Aug 2020The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration.
METHODS
Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3× per week for 3-4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments.
RESULTS
Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of ≥5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects (≥5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P < 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P < 0.05). No device-related adverse events were reported.
CONCLUSION
Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.
Topics: Aged; Aged, 80 and over; Contrast Sensitivity; Double-Blind Method; Female; Geographic Atrophy; Humans; Low-Level Light Therapy; Male; Middle Aged; Prospective Studies; Quality of Life; Retinal Drusen; Surveys and Questionnaires; Treatment Outcome; Visual Acuity; Visual Field Tests; Visual Fields
PubMed: 31404033
DOI: 10.1097/IAE.0000000000002632 -
Cold Spring Harbor Perspectives in... May 2014The formation of extracellular deposits known as drusen below the macular region of the retina correlates with increased risk of severe visual loss from age-related... (Review)
Review
The formation of extracellular deposits known as drusen below the macular region of the retina correlates with increased risk of severe visual loss from age-related macular degeneration (AMD). Inflammation and complement dysregulation contribute to AMD progression; however, disease mechanisms remain incompletely defined. Multiple genetic and environmental factors influence AMD pathology, and although immune system processes play a central role, multiple molecular mechanisms appear to be involved. Drusen proteomics, including the analyses of constituent proteins, oxidative protein modifications, and pattern recognition receptors, provide a foundation for deciphering mechanisms of drusen biogenesis and AMD pathology.
Topics: Animals; Bruch Membrane; Choroid; Disease Models, Animal; Humans; Macular Degeneration; Mice; Oxidative Stress; Proteins; Proteomics; Retinal Drusen
PubMed: 24799364
DOI: 10.1101/cshperspect.a017194 -
Eye (London, England) Jan 2021The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV),... (Review)
Review
The pachychoroid disease spectrum encompasses seven major retinal conditions including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and pachychoroid neovasculopathy or type I macular neovascularisation (MNV) secondary to chronic persistent thickening and dysfunction of the choroidal vasculature. Drusen are focal yellow-white deposits of extracellular debris, which consist of complement proteins, esterified and nonesterified cholesterol, apolipoproteins, carbohydrates, and trace elements, above the retinal pigment epithelium (RPE) or between the RPE and Bruch's membrane. Although drusen are an essential disease precursor of advanced age-related macular degeneration (AMD), a new entity "pachydrusen" has been identified to be associated with some of the enitites that constitute the pachychoroid spectrum. It remains to be determined what the exact differences are between soft drusen, pseudodrusen, and pachydrusen in terms of phenotype, genotype, and pathogenesis. Improving our knowledge in these areas will inevitably improve our understanding of their clinical significance especially as in disease prediction in AMD and the pachychroid spectrum disorders. It remains controversial whether PCV is a subtype of AMD. Understanding the pathogenesis of different types of drusen may also help in addressing if phenotype and/or genotype of type 1 MNV associated with pachychoroid are similar to type 1 MNV related to AMD. Furthermore, because pachydrusen links two pachychoroid diseases, CSC and PCV, it is also of great interest to investigate if CSC is an early stage or a predictor of PCV in future research. In this review, we share our experience in clinical practice and the latest published evidence-based literature to emphasize the differences and similarities in morphology, pathogenesis, and clinical significance of drusen and pachydrusen, a new member of the pachychoroid spectrum disorders.
Topics: Central Serous Chorioretinopathy; Choroid; Fluorescein Angiography; Humans; Retina; Retinal Drusen
PubMed: 33208847
DOI: 10.1038/s41433-020-01265-4