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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 -
International Journal of Molecular... Apr 2021High density lipoprotein (HDL) cholesterol has traditionally been considered the "good cholesterol", and most of the research regarding HDL cholesterol has for decades... (Review)
Review
High density lipoprotein (HDL) cholesterol has traditionally been considered the "good cholesterol", and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms.
Topics: Atherosclerosis; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus, Type 2; Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Macular Degeneration; Risk Factors
PubMed: 33925284
DOI: 10.3390/ijms22094547 -
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 -
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 -
Journal of Neuro-ophthalmology : the... Mar 2021Distinguishing optic disc edema from pseudopapilledema is a common, sometimes challenging clinical problem. Advances in spectral-domain optical coherence tomography... (Review)
Review
BACKGROUND
Distinguishing optic disc edema from pseudopapilledema is a common, sometimes challenging clinical problem. Advances in spectral-domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) has proven to be a cost effective, noninvasive, outpatient procedure that may help. At its core are tools that quantify the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL). The SD-OCT also provides a set of tools that may be qualitatively interpreted in the same way that we read an MRI. They include the transverse axial, en face, and circular tomogram. Our goal is to describe a practical office-based set of tools using SD-OCT in the diagnosis and monitoring of papilledema, optic disc edema, and pseudopapilledema.
EVIDENCE ACQUISITION
Searches on PubMed were performed using combinations of the following key words: OCT, papilledema, pseudopapilledema, optic disc drusen, retinal folds (RF), and choroidal folds (CF).
RESULTS
The principal elements of SD-OCT analysis of the ONH are the RNFL and GC-IPL thickness; however, these metrics have limitations when swelling is severe. Qualitative interpretation of the transverse axial SD-OCT aids in assessing peripapillary shape that may help distinguish papilledema from pseudopapilledema, evaluate atypical optic neuropathies, diagnose shunt failures, and identify outer RF and CF. There is a consensus that the SD-OCT is the most sensitive way of identifying buried optic disc drusen. En face SD-OCT is especially effective at detecting peripapillary wrinkles and outer retinal creases, both of which are common and distinctive signs of optic disc edema that rule out pseudopapilledema. Mechanically stressing the ONH in the adducted eye position, in patients with papilledema, may expose folds and peripapillary deformations that may not be evident in primary position. We also discuss how to optimize the acquisition and registration of SD-OCT images.
CONCLUSIONS
The SD-OCT is not a substitute for a complete history and a careful examination. It is, however, a convenient ancillary test that aids in the diagnosis and management of papilledema, optic disc edema, and pseudopapilledema. It is particularly helpful in monitoring changes over the course of time and distinguishing low-grade papilledema from buried drusen. The application of the SD-OCT toolbox depends on optimizing the acquisition of images, understanding its limitations, recognizing common artifacts, and accurately interpreting images in the context of both history and clinical findings.
Topics: Eye Diseases, Hereditary; Humans; Nerve Fibers; Optic Disk; Optic Nerve Diseases; Papilledema; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 32909979
DOI: 10.1097/WNO.0000000000001078 -
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