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Mechanisms of Ageing and Development Oct 2020Ageing of the retina is associated with the gradual accumulation of basal deposits and the formation of drusen. However, in some individuals this process is exacerbated... (Meta-Analysis)
Meta-Analysis
Ageing of the retina is associated with the gradual accumulation of basal deposits and the formation of drusen. However, in some individuals this process is exacerbated and causes development of age-related macular degeneration. Late features of age-related macular degeneration include geographic atrophy of the neuroretina or choroidal neovascularization. Such changes lead to blurred vision, metamorphopsia, and scotoma, and is the leading cause of vision loss in developed countries. Chronic low-grade inflammation has been investigated because of its relationship to ageing and its role in the gap between chronological and biological ageing. Here, we systematically reviewed studies investigating systemic C-reactive protein in patients with age-related macular degeneration. We identified 53 studies with 60,598 participants (10,392 patients and 38,901 controls). Our meta-analyses revealed that early age-related macular degeneration was not associated to systemic C-reactive protein (Cohen's d = 0.03 [-0.04 to 0.10]; OR = 1.06 [0.93-1.20]; P = 0.39) whereas late age-related macular degeneration (Cohen's d = 0.38 [0.24 to 0.51]; OR = 1.99 [1.55-2.52]; P < 0.0001), and neovascular age-related macular degeneration (Cohen's d = 0.40 [0.24 to 0.56]; OR = 2.07 [1.55-2.76]; P < 0.0001) was associated with a small-to-moderate increase in systemic C-reactive protein. Our review provides an overview of this extensively studied field, provide summary estimates that provide insight into when and to what extent systemic C-reactive protein is associated with age-related macular degeneration, and help in distinguishing the potentially reversible disease processes from that of irreversible retinal ageing.
Topics: Aging; C-Reactive Protein; Geographic Atrophy; Humans; Retinitis
PubMed: 32937187
DOI: 10.1016/j.mad.2020.111353 -
International Ophthalmology Aug 2020Optic disc drusen (ODD) are acellular deposits in the prelaminar optic nerve head. The most accredited theory is that they are secondary to abnormalities in axonal... (Review)
Review
BACKGROUND
Optic disc drusen (ODD) are acellular deposits in the prelaminar optic nerve head. The most accredited theory is that they are secondary to abnormalities in axonal metabolism and degeneration, but the pathogenesis is not clear to date.
CLINICAL MANIFESTATION
Although ODD are often considered a benign condition, the great majority of patients with ODD show visual field defects and are at higher risk for developing anterior ischemic optic neuropathy. ODD are classified as superficial or buried, with the latter being often misdiagnosed as papilledema with optic nerve head swelling, leading to an unnecessary investigation for causes of increased intracranial pressure.
AIM
The recent technological improvements in OCT imaging which allowed an earlier and more certain diagnosis even of the smallest ODD, renovated the interest around this pathology. However, an updated systematic review is still missing. Therefore, the aim of this work is to provide a concise yet comprehensive overview of the current state of art, focusing on pathophysiology, clinical presentation, diagnostic methods, treatment modalities and potential future perspectives of this condition.
Topics: Humans; Optic Disk; Optic Disk Drusen; Optic Neuropathy, Ischemic; Papilledema; Visual Field Tests
PubMed: 32383130
DOI: 10.1007/s10792-020-01365-w -
Ophthalmology. Retina Sep 2019Age-related macular degeneration (AMD) is highly prevalent among the elderly. We systematically reviewed the literature to provide an overview of ultra-widefield imaging... (Meta-Analysis)
Meta-Analysis
TOPIC
Age-related macular degeneration (AMD) is highly prevalent among the elderly. We systematically reviewed the literature to provide an overview of ultra-widefield imaging (UWFI) of peripheral retinal lesions in AMD.
CLINICAL RELEVANCE
Information regarding retinal characteristics and prevalence of AMD is based mainly on studies using color photography of the central retina, where early and potentially severe manifestations of the disease are found. However, this approach has the effect of neglecting the periphery. Studies using UWFI provide new evidence to show that clinical features associated with AMD are not exclusive to the area of the macula.
METHODS
Eligible studies had to detect lesions of the peripheral retina (based on the original definition of a standard macular grid, with the addition of 2 zones classed as peripheral) using UWFI in eyes with AMD. Ultra-widefield imaging included pseudocolor photography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Eligibility was restricted to human participants and studies written in English. We searched the bibliographic databases PubMed, the Cochrane Library, EMBASE, and the Web of Science on March 27, 2018. We calculated the prevalence of peripheral findings in eyes with AMD and performed similar meta-analyses on the healthy control group. A random-effects model was used because of possible study heterogeneity.
RESULTS
Twelve studies were eligible for the review, which included 3261 or more eyes. Studies were clinic based, apart from 1 study that was a random population sample of individuals 62 years of age or older. Studies were cross-sectional in nature, apart from 1 case-control study. The peripheral lesions most commonly observed were drusen, atrophy, and changes to the retinal pigment epithelium. In eyes with AMD, peripheral lesions were found in 82.7% of eyes (confidence interval, 78.4%-86.7%) compared with 33.3% of healthy eyes (confidence interval, 28.3%-38.5%).
CONCLUSIONS
Peripheral changes were found to be highly prevalent in eyes with AMD, supporting the claim that the disease is panretinal and not macula only. The clinical significance of peripheral lesions in AMD remains incompletely understood, and therefore, further UWFI studies are recommended.
Topics: Aged; Aged, 80 and over; Female; Humans; Macular Degeneration; Male; Middle Aged; Optical Imaging; Retina
PubMed: 31167730
DOI: 10.1016/j.oret.2019.04.014 -
Ophthalmic Surgery, Lasers & Imaging... Mar 2019Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly in developed countries. Subthreshold retinal laser therapy is a...
BACKGROUND AND OBJECTIVE
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly in developed countries. Subthreshold retinal laser therapy is a new technique that targets drusen - a marker of nonexudative AMD - without causing incidental retinal damage associated with conventional laser photocoagulation. This review summarizes published literature on subthreshold retinal laser therapy as prophylactic treatment of nonexudative AMD.
PATIENTS AND METHODS
A literature search of the PubMed, Medline, and Embase databases was conducted from January 1997 to April 2018. Studies were analyzed based upon study design, laser parameters, drusen reduction, changes in visual acuity (VA), and the development of choroidal neovascularization (CNV) and/or geographic atrophy (GA).
RESULTS
Twelve studies involving 2,481 eyes treated with subthreshold retinal laser therapy were included in this review. Treatment led to increased drusen reduction, and studies with significant VA improvement were associated with significant drusen reduction. There was no significant change in the risk of developing CNV or GA.
CONCLUSIONS
Subthreshold retinal laser therapy is effective for reducing drusen and potentially improving vision in patients with nonexudative AMD. This therapy does not show benefits in reducing development of CNV or GA. Thus, its long-term efficacy to prevent progression to advanced AMD cannot yet be recommended. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e61-e70.].
Topics: Choroidal Neovascularization; Disease Progression; Geographic Atrophy; Humans; Laser Coagulation; Macular Degeneration; Retinal Drusen; Visual Acuity
PubMed: 30893458
DOI: 10.3928/23258160-20190301-13 -
Acta Ophthalmologica Sep 2019Age-related macular degeneration (AMD) is aetiologically linked to immunological ageing and dysfunction. One aspect of this is the altered neutrophil-to-lymphocyte ratio... (Meta-Analysis)
Meta-Analysis
Age-related macular degeneration (AMD) is aetiologically linked to immunological ageing and dysfunction. One aspect of this is the altered neutrophil-to-lymphocyte ratio (NLR), which in other domains have been associated with inflammation and angiogenesis, and therefore investigated in patients with AMD in several papers. In this systematic review and meta-analysis, we summarize findings in patients with AMD in relation to NLR, both qualitatively and quantitatively. We searched PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central and identified six studies from where we extracted data on 1178 individuals (777 patients with AMD and 401 healthy controls). Patients with AMD had a higher NLR (weighted mean difference: 0.37, CI 95% 0.08 to 0.66, p = 0.013) when compared to healthy controls. In subgroup analyses, we did not find a significant difference between patients with dry AMD and healthy controls (weighted mean difference: 0.34, CI 95% -0.03 to 0.69, p = 0.068), but did find a strong significant difference between patients with neovascular AMD and healthy controls (weighted mean difference: 0.54, CI 95% 0.23 to 0.86, p = 0.00068). Hence, we find that the association between AMD and elevated NLR may have stronger relevance to the neovascular subtype of AMD. However, the clinical value of measuring the NLR remains unclear.
Topics: Humans; Immunity, Cellular; Lymphocytes; Neutrophils; Wet Macular Degeneration
PubMed: 30811869
DOI: 10.1111/aos.14072 -
Survey of Ophthalmology 2019The rising prevalence of age-related eye diseases, particularly age-related macular degeneration, places an ever-increasing burden on health care providers. As new...
The rising prevalence of age-related eye diseases, particularly age-related macular degeneration, places an ever-increasing burden on health care providers. As new treatments emerge, it is necessary to develop methods for reliably assessing patients' disease status and stratifying risk of progression. The presence of drusen in the retina represents a key early feature in which size, number, and morphology are thought to correlate significantly with the risk of progression to sight-threatening age-related macular degeneration. Manual labeling of drusen on color fundus photographs by a human is labor intensive and is where automatic computerized detection would appreciably aid patient care. We review and evaluate current artificial intelligence methods and developments for the automated detection of drusen in the context of age-related macular degeneration.
Topics: Algorithms; Diagnostic Techniques, Ophthalmological; Humans; Image Processing, Computer-Assisted; Macular Degeneration; Photography; Retinal Drusen
PubMed: 30772363
DOI: 10.1016/j.survophthal.2019.02.003 -
Retina (Philadelphia, Pa.) Dec 2018Polypoidal choroidal vasculopathy (PCV) is a disease with significant inter-ethnical differences. In this study, we systematically review the literature on the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Polypoidal choroidal vasculopathy (PCV) is a disease with significant inter-ethnical differences. In this study, we systematically review the literature on the prevalence of PCV in whites referred with a diagnosis of exudative age-related macular degeneration (AMD).
METHODS
We searched PubMed, Embase, the Cochrane Library, and the Web of Science on 24 March, 2017 for studies evaluating the prevalence of PCV in white patients with exudative AMD. Data extraction and risk of bias assessments were performed in duplicate. Studies were included for a qualitative review and a meta-analysis, including subgroup analysis for differences in age and sex.
RESULTS
We included data from 11 studies (>2,200 participants). For diagnosis, indocyanine green angiography was used together with a set of supporting criteria on fundus examination and optical coherence tomography. Extramacular location was more prevalent in eyes with PCV. Drusen was present in the fellow eye in 17% to 27%. Pooled prevalence of PCV in white patients with exudative AMD was 8.7% (confidence interval 95%: 7.2%-10.3%). Patients with PCV were 3.7 years (confidence interval 95%: 2.1 years-5.3 years) younger than those with other exudative AMD. Sex did not differ significantly.
CONCLUSION
Polypoidal choroidal vasculopathy is not a rare subtype of exudative AMD in whites-it is present in approximately one in 11 patients.
Topics: Choroid; Choroid Diseases; Fluorescein Angiography; Fundus Oculi; Global Health; Humans; Macula Lutea; Polyps; Prevalence; Tomography, Optical Coherence; Wet Macular Degeneration
PubMed: 29059101
DOI: 10.1097/IAE.0000000000001872 -
Translational Vision Science &... Jul 2017To assess the quality of optical coherence tomography (OCT) grading algorithms for retinal biomarkers of age-related macular degeneration (AMD). (Review)
Review
PURPOSE
To assess the quality of optical coherence tomography (OCT) grading algorithms for retinal biomarkers of age-related macular degeneration (AMD).
METHODS
Following a systematic review of the literature data on detection and quantification of AMD retinal biomarkers by available algorithms were extracted and descriptively synthesized. Algorithm quality was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 checklist with a focus on accuracy against established reference standards and risk of bias.
RESULTS
Thirty five studies reporting computer-aided diagnosis (CAD) tools for qualitative analysis or algorithms for quantitative analysis were identified. Compared with manual assessment in reference standards correlation coefficients ranged from 0.54 to 0.97 for drusen, 0.80 to 0.98 for geographic atrophy (GA), and 0.30 to 0.98 for intra- or subretinal fluid and pigment epithelial detachment (PED) detection by automated algorithms. CAD tools achieved area under the curve (AUC) values of 0.94 to 0.99, sensitivity of 0.90 to 1.00, and specificity of 0.89 to 0.92.
CONCLUSIONS
Automated analysis of AMD biomarkers on OCT is promising. However, most of the algorithm validation was performed in preselected patients, exhibiting the targeted biomarker only. In addition, type and quality of reported algorithm validation varied substantially.
TRANSLATIONAL RELEVANCE
The development of algorithms for combined, simultaneous analysis of multiple AMD biomarkers including AMD staging and the agreement on standardized validation procedures would be of considerable translational value for the clinician and the clinical researcher.
PubMed: 28729948
DOI: 10.1167/tvst.6.4.10 -
The Cochrane Database of Systematic... Feb 2017Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract surgery is an effective treatment for cataract-induced visual loss, some clinicians suspect that such an intervention may increase the risk of worsening of underlying AMD and thus have deleterious effects on vision.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of cataract surgery compared with no surgery in eyes with AMD.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 December 2016.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials that enrolled participants whose eyes were affected by both cataract and AMD in which cataract surgery was compared with no surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated the search results against the inclusion and exclusion criteria. Two review authors independently extracted data, assessed risk of bias for included studies, and graded the certainty of evidence. We followed methods as recommended by Cochrane.
MAIN RESULTS
We included two RCTs with a total of 114 participants (114 study eyes) with visually significant cataract and AMD. We identified no ongoing trials. Participants in each RCT were randomized to immediate cataract surgery (within two weeks of enrollment) or delayed cataract surgery (six months after enrollment). The risk of bias was unclear for most domains in each study; one study was registered prospectively.In one study conducted in Australia outcomes were reported only at six months (before participants in the delayed-surgery group had cataract surgery). At six months, the immediate-surgery group showed mean improvement in best-corrected visual acuity (BCVA) compared with the delayed-surgery group (mean difference (MD) -0.15 LogMAR, 95% confidence interval (CI) -0.28 to -0.02; 56 participants; moderate-certainty evidence). In the other study, conducted in Austria, outcomes were reported only at 12 months (12 months after participants in the immediate-surgery group and six months after participants in the delayed-surgery group had cataract surgery). There was uncertainty as to which treatment group had better improvement in distance visual acuity at 12 months (unit of measure not reported; very low-certainty evidence).At 12 months, the mean change from baseline between groups in cumulated drusen or geographic atrophy area size was small and there was uncertainty which, if either, of the groups was favored (MD 0.76, 95% CI -8.49 to 10.00; 49 participants; low-certainty evidence). No participant in one study had exudative AMD develop in the study eye during 12 months of follow-up; in the other study, choroidal neovascularization developed in the study eye of 1 of 27 participants in the immediate-surgery group versus 0 of 29 participants in the delayed-surgery group at six months (risk ratio 3.21, 95% CI 0.14 to 75.68; 56 participants; very low-certainty evidence). Quality of life was measured using two different questionnaires. Scores on the Impact of Vision Impairment (IVI) questionnaire suggested that the immediate-surgery group fared better regarding vision-related quality of life than the delayed-surgery group at six months (MD in IVI logit scores 1.60, 95% CI 0.61 to 2.59; low-certainty evidence). However, we could not analyze scores from the Visual Function-14 (VF-14) questionnaire from the other study due to insufficient data. No postoperative complication was reported from either study.
AUTHORS' CONCLUSIONS
At this time, it is not possible to draw reliable conclusions from the available data as to whether cataract surgery is beneficial or harmful in people with AMD after 12 months. Although cataract surgery provides short-term (six months) improvement in BCVA in eyes with AMD compared with no surgery, it is unclear whether the timing of surgery has an effect on long-term outcomes. Physicians must make recommendations to their AMD patients regarding cataract surgery based on experience and clinical judgment until large controlled trials are conducted and their findings published.There is a need for prospective RCTs in which cataract surgery is compared with no surgery in people with AMD to better evaluate whether cataract surgery is beneficial or harmful in all or a subset of AMD patients. However, ethical considerations preclude withholding surgery, or delaying it for several years, if it may be a potentially beneficial treatment. Designers of future trials are encouraged to utilize existing standardized systems for grading cataract and AMD and for measuring key outcomes: visual acuity, change in visual acuity, worsening of AMD, quality of life measures, and adverse events.
Topics: Cataract; Cataract Extraction; Disease Progression; Humans; Macular Degeneration; Middle Aged; Randomized Controlled Trials as Topic; Time Factors; Visual Acuity
PubMed: 28206671
DOI: 10.1002/14651858.CD006757.pub4 -
The Cochrane Database of Systematic... Aug 2016Age-related macular degeneration (AMD) is a progressive, late-onset disorder of the macula affecting central vision. It is the leading cause of blindness in people over... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a progressive, late-onset disorder of the macula affecting central vision. It is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown that AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD.
OBJECTIVES
The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2016), EMBASE (January 1980 to March 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2016), PubMed (January 1946 to March 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 5 June 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 31 March 2016.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials that compared statins with other treatments, no treatment, or placebo in people who were diagnosed as having the early stages of AMD.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes between the included studies.
MAIN RESULTS
Two RCTs with a total of 144 participants met the selection criteria. Both trials compared simvastatin versus placebo in older people (older than 50 or 60 years) with high risk of developing AMD (drusen present on examination). Overall, we judged the quality of the evidence to be low, as we downgraded all outcomes due to limitations in the designs of the trials and insufficient outcome reporting. The larger trial, with 114 participants, was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked, however data were missing for 30% of participants at three years' follow-up. The smaller trial, with 30 participants, was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias.Neither trial reported data for change in visual acuity. Low-quality evidence from the smaller trial, with 30 participants, did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups.Preliminary analyses of 42 participants who had completed 12 months' follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years' follow-up were not reported. At three years, low-quality evidence showed an effect of simvastatin in slowing progression of AMD compared with placebo to be uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09).One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis.
AUTHORS' CONCLUSIONS
Evidence from currently available RCTs is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD.
Topics: Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Macular Degeneration; Male; Middle Aged; Randomized Controlled Trials as Topic; Simvastatin; Visual Acuity
PubMed: 27490232
DOI: 10.1002/14651858.CD006927.pub5