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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 -
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 -
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 -
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 -
Indian Journal of Ophthalmology Aug 2023
Topics: Humans; Retina; Optic Disk Drusen
PubMed: 37530259
DOI: 10.4103/IJO.IJO_3019_22 -
Nature Communications Dec 2021Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment...
Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE) and atrophy of the RPE monolayer in advanced disease stages - leading to photoreceptor cell death and vision loss. Currently, there are no drugs that stop drusen formation or RPE atrophy in AMD. Here we provide an iPSC-RPE AMD model that recapitulates drusen and RPE atrophy. Drusen deposition is dependent on AMD-risk-allele CFH(H/H) and anaphylatoxin triggered alternate complement signaling via the activation of NF-κB and downregulation of autophagy pathways. Through high-throughput screening we identify two drugs, L-745,870, a dopamine receptor antagonist, and aminocaproic acid, a protease inhibitor that reduce drusen deposits and restore RPE epithelial phenotype in anaphylatoxin challenged iPSC-RPE with or without the CFH(H/H) genotype. This comprehensive iPSC-RPE model replicates key AMD phenotypes, provides molecular insight into the role of CFH(H/H) risk-allele in AMD, and discovers two candidate drugs to treat AMD.
Topics: Alleles; Aminocaproic Acid; Complement Factor H; Drug Evaluation, Preclinical; Humans; Induced Pluripotent Stem Cells; Macular Degeneration; Models, Biological; Phenotype; Pyridines; Pyrroles; Retinal Pigment Epithelium
PubMed: 34911940
DOI: 10.1038/s41467-021-27488-x -
Taiwan Journal of Ophthalmology 2022A wide spectrum of phenotypic manifestations characterizes age-related macular degeneration (AMD). Drusen is considered the hallmark of AMD and is located underneath the... (Review)
Review
A wide spectrum of phenotypic manifestations characterizes age-related macular degeneration (AMD). Drusen is considered the hallmark of AMD and is located underneath the retinal pigment epithelium (RPE). In contrast, subretinal drusenoid deposits (SDDs), also known as reticular pseudodrusens, are located in the subretinal space, on top of the RPE. SDDs are poorly detected by clinical examination and color fundus photography. Multimodal imaging is required for their proper diagnosis. SDDs are topographically and functionally related to rods. SDDs cause a deep impairment in retinal sensitivity and dark adaptation. SDDs are dynamic structures that may grow, fuse with each other, or regress over time. An intermediate step in some eyes is the development of an acquired vitelliform lesion. The presence of SDD confers an eye a high risk for the development of late AMD. SDD leads to macular neovascularization, particularly type 3, geographic atrophy, and outer retinal atrophy.
PubMed: 35813798
DOI: 10.4103/tjo.tjo_18_22