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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 -
Autophagy Oct 2023Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the...
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the primary impairment of AMD. The earliest clinical hallmark of AMD is drusen, which are yellowish spots mainly composed of lipid droplets (LDs) accumulated under the retinal pigment epithelium (RPE). However, the potential pathogenic role of this excessive LD accumulation in AMD is yet to be determined, partially due to a lack of chemical tools to manipulate LDs specifically. Here, we employed our recently developed Lipid Droplets·AuTophagy Tethering Compounds (LD∙ATTECs) to degrade LDs and to evaluate its consequence on the AMD-like phenotypes in apoe (apolipoprotein E; B6/JGpt-Apoe/Gpt) mouse model. apoe mice fed with high-fat diet (apoe-HFD) exhibited excessive LD accumulation in the retina, particularly with AMD-like phenotypes including RPE degeneration, Bruch's membrane (BrM) thickening, drusen-like deposits, and photoreceptor dysfunction. LD·ATTEC treatment significantly cleared LDs in RPE/choroidal tissues without perturbing lipid synthesis-related proteins and rescued RPE degeneration and photoreceptor dysfunction in apoe-HFD mice. This observation implied a causal relationship between LD accumulation and AMD-relevant phenotypes. Mechanically, the apoe-HFD mice exhibited elevated oxidative stress and inflammatory signals, both of which were mitigated by the LD·ATTEC treatment. Collectively, this study demonstrated that LD accumulation was a trigger for the process of AMD and provided entry points for the treatment of the initial insult of AMD by degrading LDs. AMD: age-related macular degeneration; : apolipoprotein E; ATTECs: autophagy-tethering compounds; BODIPY: boron-dipyrromethene; BrM: Bruch's membrane; ERG: electroretinogram; HFD: high-fat diet; LD·ATTECs: Lipid Droplets·AuTophagy Tethering Compounds; LDs: lipid droplets; OA: oleic acid; OPL: outer plexiform layer; ROS: reactive oxygen species; RPE: retinal pigment epithelium.
Topics: Mice; Animals; Lipid Droplets; Autophagy; Macular Degeneration; Retinal Pigment Epithelium; Apolipoproteins E; Phenotype; Apolipoproteins
PubMed: 37266932
DOI: 10.1080/15548627.2023.2220540 -
Eye (London, England) Jan 2021Optical coherence tomography (OCT) is a non-invasive medical imaging technology that is playing an increasing role in the routine assessment and management of patients... (Review)
Review
Optical coherence tomography (OCT) is a non-invasive medical imaging technology that is playing an increasing role in the routine assessment and management of patients with neuro-ophthalmic conditions. Its ability to characterise the optic nerve head, peripapillary retinal nerve fibre layer and cellular layers of the macula including the ganglion cell layer enables qualitative and quantitative assessment of optic nerve disease. In this review, we discuss technical features of OCT and OCT-based imaging techniques in the neuro-ophthalmic context, potential pitfalls to be aware of, and specific applications in more common neuro-ophthalmic conditions including demyelinating, inflammatory, ischaemic and compressive optic neuropathies, optic disc drusen and raised intracranial pressure. We also review emerging applications of OCT angiography within neuro-ophthalmology.
Topics: Humans; Ophthalmology; Optic Disk; Optic Disk Drusen; Optic Nerve Diseases; Tomography, Optical Coherence
PubMed: 33239763
DOI: 10.1038/s41433-020-01288-x -
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 -
Medicina (Kaunas, Lithuania) Mar 2023: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses... (Review)
Review
: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses light in the infrared spectrum. The laser light penetrates into the deep retinal layers and the choroid. Retromode images are captured with a laterally displaced aperture, and the detector captures only the scattered light. The result is a high-contrast pseudo-three-dimensional image. Age-related macular degeneration (AMD) is a disabling retinal disease. AMD is characterized in its early stage by small and intermediate drusen formation, while the signs of intermediate AMD are large drusen and/or pigmentary abnormalities. Late AMD has two forms, geographic atrophy, which is the advanced form of dry AMD, and wet AMD. Most of the lesions of AMD are located in the outer layers of the retina. This new imaging method can provide a glimpse of the deep retinal layers' topographic changes in a non-invasive, fast, and effective way that can match the other imaging tools available. : The literature review was performed by searching the PubMed database using the following combination of keywords: retromode imaging and age-related macular degeneration. Relevant images similar to the ones in the literature were identified and used as models. : The purpose of this article is to highlight the utility of incorporating retromode imaging into the multimodal evaluation of the retina in patients with AMD and to gather and integrate these findings into a brief but comprehensive paper. Retromode imaging is a good screening, diagnosis, and monitoring tool for patients with AMD.
Topics: Humans; Retina; Wet Macular Degeneration; Tomography, Optical Coherence
PubMed: 37109604
DOI: 10.3390/medicina59040647 -
Antioxidants (Basel, Switzerland) Sep 2021Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by... (Review)
Review
Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber's hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.
PubMed: 34679672
DOI: 10.3390/antiox10101538