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Ophthalmology and Therapy Mar 2021Dark adaptation (DA) has been proposed as a possible functional biomarker for age-related macular degeneration (AMD). In this systematic review we aim to evaluate... (Review)
Review
INTRODUCTION
Dark adaptation (DA) has been proposed as a possible functional biomarker for age-related macular degeneration (AMD). In this systematic review we aim to evaluate current methodology used to assess DA in people with AMD, the evidence of precision in detecting the onset and progression of AMD, and the relationship between DA and other functional and structural measures.
METHODS
MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, PsycARTICLES were searched for studies published between January 2006 and January 2020 that assessed DA in people with AMD. Details of eligible studies including study design, characteristics of study population and outcomes were recorded. All included studies underwent quality appraisal using approved critical appraisal tools. This systematic review follows PRISMA guidelines (PROSPERO registration number: CRD42019129486).
RESULTS
Forty-eight studies were eligible for inclusion, reporting a variety of instruments and protocols to assess different DA parameters. Twenty of these studies used the AdaptDx (MacuLogix, Hummelstown, PA, USA) instrument and assessed rod-intercept time (RIT). Most of these reported that RIT was delayed in people with AMD and this delay worsened with AMD severity. Four studies, involving 533 participants, reported estimates of diagnostic performance of AdaptDx to separate people with AMD from visually healthy controls. DA has been compared to other measures of visual function, patient-reported outcome measures (PROMs) and structural measures. Ten studies specifically considered evidence that the presence of certain structural abnormalities was associated with impaired DA in AMD.
CONCLUSIONS
This systematic review indicates overwhelming evidence of reasonable quality for an association between impaired DA and AMD. Data on the repeatability and reproducibility of DA measurement are sparse. There is evidence that structural abnormalities such as reticular drusen are associated with prolongation of DA time. Fewer studies have explored an association between DA and other measures of visual function or PROMs. We found no studies that had compared DA with performance-based measures.
PubMed: 33565038
DOI: 10.1007/s40123-020-00323-0 -
Eye (London, England) Jan 2024The full-field stimulus threshold (FST) is a psychophysical measure of whole-field retinal light sensitivity. It can assess residual visual function in patients with... (Review)
Review
The full-field stimulus threshold (FST) is a psychophysical measure of whole-field retinal light sensitivity. It can assess residual visual function in patients with severe retinal disease and is increasingly being adopted as an endpoint in clinical trials. FST applications in routine ophthalmology clinics are also growing, but as yet there is no formalised standard guidance for measuring FST. This scoping review explored current variability in FST conduct and reporting, with an aim to inform further evidence synthesis and consensus guidance. A comprehensive electronic search and review of the literature was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) checklist. Key source, participant, methodology and outcomes data from 85 included sources were qualitatively and quantitatively compared and summarised. Data from 85 sources highlight how the variability and insufficient reporting of FST methodology, including parameters such as units of flash luminance, colour, duration, test strategy and dark adaptation, can hinder comparison and interpretation of clinical significance across centres. The review also highlights an unmet need for paediatric-specific considerations for test optimisation. Further evidence synthesis, empirical research or structured panel consultation may be required to establish coherent standardised guidance on FST methodology and context or condition dependent modifications. Consistent reporting of core elements, most crucially the flash luminance equivalence to 0 dB reference level is a first step. The development of criteria for quality assurance, calibration and age-appropriate reference data generation may further strengthen rigour of measurement.
Topics: Humans; Child; Retina; Vision, Ocular; Dark Adaptation; Retinal Diseases; Checklist
PubMed: 37443335
DOI: 10.1038/s41433-023-02636-3 -
Eye (London, England) Jun 2021To conduct a systematic review and meta-analysis on data related to macular pigment optical density (MPOD) and visual function in adults with healthy eyes. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To conduct a systematic review and meta-analysis on data related to macular pigment optical density (MPOD) and visual function in adults with healthy eyes.
METHODS
MEDLINE®, Cochrane, and Commonwealth of Agriculture Bureau abstracts databases were searched for English-language publications between 1946 and August 2018. Included studies examined correlation of MPOD and visual function in adults with healthy eyes at all timepoints and all designs, except for case-control, case reports, and reviews. Visual function outcomes of interest included photostress recovery, contrast sensitivity, visual acuity, glare sensitivity/disability, and dark adaptation. Random effects model meta-analyses combined study-level correlation (r).
RESULTS
Twenty-two publications were included. In meta-analysis MPOD was found to be significantly correlated with contrast sensitivity at 30' (two studies, summary r: 0.37; 95% CI 0.15, 0.56), and at 1° eccentricity with a spatial frequency of 7, 11, and 21 cpd (three studies, summary r: 0.31; 95% CI 0.06, 0.52), with photostress recovery at a 1° eccentricity with a moderate background, 10 cpd, and 16% contrast (two studies, summary r: -0.17; 95% CI -0.31, -0.02), and at 30' (four studies, summary r: -0.57; 95% CI -0.78, -0.24), and with glare disability at 30' eccentricity with a log scale at 460 nm (three studies, summary r = 0.47; 95% CI 0.32; 0.59). There were insufficient data for meta-analysis for other visual functions.
CONCLUSIONS
Our review identifies a link between MPOD and visual function with significant correlations with photostress recovery, glare disability, and contrast sensitivity.
Topics: Adult; Contrast Sensitivity; Glare; Humans; Lutein; Macula Lutea; Macular Pigment; Visual Acuity; Zeaxanthins
PubMed: 32792595
DOI: 10.1038/s41433-020-01124-2 -
Eye (London, England) Jan 2020This article is a systematic review of evidence regarding the impact of different lighting conditions on the vision and quality of life (QoL) of people with primary... (Review)
Review
This article is a systematic review of evidence regarding the impact of different lighting conditions on the vision and quality of life (QoL) of people with primary open-angle glaucoma (POAG). A systematic literature search was carried out using CINAHL, MEDLINE, PsycARTICLES, PsycINFO, Embase, and Ovid Nursing Database for studies: published up to April 2019; including people diagnosed with POAG; and assessing visual function or QoL in response to changing lighting/luminance levels or glare. Two researchers independently screened studies for eligibility. Data were extracted from eligible studies regarding study design, participant characteristics, outcomes, and results. Quality of included studies was critically appraised. Of 8437 studies, 56 eligible studies were included. Studies investigated the effects of lighting on the following domains among people with POAG: QoL (18/56), psychophysical measures (16/56), functional vision (10/56), activities of daily living (10/56), and qualitative findings (2/56). POAG negatively affects low-luminance contrast sensitivity, glare symptoms, and dark adaptation time and extent. In vision-related QoL questionnaires, people with POAG report problems with lighting, glare, and dark adaptation more frequently than any other domain. These problems worsen with progressing visual field loss. Early-stage POAG patients experience significantly more difficulties in low-luminance or changing lighting conditions than age-matched controls (AMCs), challenging perceptions of early-stage POAG as asymptomatic. However, performance-based studies seldom show significant differences between POAG participants and AMCs on tasks simulating daily activities under non-optimal lighting conditions. Further research with larger samples is required to optimise ambient and task-oriented lighting that can support patients' adaptation to POAG.
Topics: Activities of Daily Living; Glaucoma; Glaucoma, Open-Angle; Humans; Lighting; Quality of Life; Visual Acuity
PubMed: 31822854
DOI: 10.1038/s41433-019-0679-5 -
Biology of Sport Dec 2012To develop a systematic review to evaluate, through the best scientific evidence available, the effectiveness of aerobic exercise in improving the biomechanical... (Review)
Review
To develop a systematic review to evaluate, through the best scientific evidence available, the effectiveness of aerobic exercise in improving the biomechanical characteristics of tendons in experimental animals. Two independent assessors conducted a systematic search in the databases Medline/PUBMED and Lilacs/BIREME, using the following descriptors of Mesh in animal models. The ultimate load of traction and the elastic modulus tendon were used as primary outcomes and transverse section area, ultimate stress and tendon strain as secondary outcomes. The assessment of risk of bias in the studies was carried out using the following methodological components: light/dark cycle, temperature, nutrition, housing, research undertaken in conjunction with an ethics committee, randomization, adaptation of the animals to the training and preparation for the mechanical test. Eight studies, comprising 384 animals, were selected; it was not possible to combine them into one meta-analysis due to the heterogeneity of the samples. There was a trend to increasing ultimate load without changes in the other outcomes studied. Only one study met more than 80% of the quality criteria. Physical training performed in a structured way with imposition of overloads seems to be able to promote changes in tendon structure of experimental models by increasing the ultimate load supported. However, the results of the influence of exercise on the elastic modulus parameters, strain, transverse section area and ultimate stress, remain controversial and inconclusive. Such a conclusion must be evaluated with reservation as there was low methodological control in the studies included in this review.
PubMed: 24868114
DOI: 10.5604/20831862.1019661 -
Acta Ophthalmologica Dec 2020The aim of this systematic review was to compare certain side-effects [visual fields (VF), dark adaptation, colour vision (CV) and contrast sensitivity (CS)] of...
The aim of this systematic review was to compare certain side-effects [visual fields (VF), dark adaptation, colour vision (CV) and contrast sensitivity (CS)] of conventional panretinal photocoagulation (PRP) with those of other treatments in proliferative diabetic retinopathy (PDR). A systematic literature search was conducted on 30 November 2018 in PubMed and Embase. The search comprised the keywords 'proliferative diabetic retinopathy', 'laser', 'treatment' and 'anti-vegf'. We included prospective studies and randomized controlled trials that investigated certain side-effects (VF, dark adaptation, CV, CS) in treatment of PDR (primary outcome). In total, 1867 articles were screened, and 10 studies were included (2176 eyes of 2086 patients examined in the VF studies and 1360 eyes of 1360 patients examined in the CV and CS studies). Visual fields (VF) were investigated in 10 studies, CV in one study and CS in one study. Treatment modalities included conventional PRP, other modalities of laser treatment and vascular endothelial growth factor (VEGF) inhibitors. Four studies demonstrated a worse VF impact of PRP than VEGF inhibitors. Seven studies reported of an overall worsening in VF after laser with no differences between different laser approaches. No differences were found in CV or CS. Overall, we found a trend, confirmed in four large studies, towards VEGF inhibitors causing less harm to VF compared to conventional PRP. Whilst VF was generally depressed after laser, it did not differ between different treatment approaches. Furthermore, it was not possible to make certain conclusions of CV or CS, with only one study in each field.
Topics: Angiogenesis Inhibitors; Diabetic Retinopathy; Humans; Intravitreal Injections; Laser Coagulation; Vascular Endothelial Growth Factor A; Visual Acuity; Visual Fields
PubMed: 32421255
DOI: 10.1111/aos.14474 -
The Cochrane Database of Systematic... Dec 2020Age-related macular degeneration (AMD) is a highly prevalent condition in an ever-increasing elderly population. Although insidious in the early stages, advanced AMD... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is a highly prevalent condition in an ever-increasing elderly population. Although insidious in the early stages, advanced AMD (neovascular and atrophic forms) can cause significant visual disability and economic burden on health systems worldwide. The most common form, geographic atrophy, has no effective treatment to date, whereas neovascular AMD can be treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Geographic atrophy has a slow disease progression and patients tend to have preserved central vision until the final stages. This tendency, coupled with the use of modern imaging modalities, provides a large window of opportunity to intervene with validated methods to assess treatment efficacy. As geographic atrophy is an increasingly common condition with no effective intervention, many treatments are under investigation, one of which is visual cycle modulators. These medications have been shown to reduce lipofuscin accumulation in pre-clinical studies that have led to several clinical trials, reviewed herein.
OBJECTIVES
To assess the efficacy and safety of visual cycle modulators for the prevention and treatment of geographic atrophy secondary to AMD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); MEDLINE Ovid; Embase Ovid; Web of Science Core Collection; Scopus; Association for Research in Vision and Ophthalmology (ARVO) website; ClinicalTrials.gov and the WHO ICTRP to 11 January 2020 with no language restrictions. We also searched using the reference lists of reviews and existing studies and the Cited Reference Search function in Web of Science to identify further relevant studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-randomised clinical studies (if available) that compared visual cycle modulators to placebo or no treatment (observation) in people diagnosed with AMD (early, intermediate or geographic atrophy).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risk of bias in the included studies and extracted data. Both authors entered data into RevMan 5. We resolved discrepancies through discussion. We graded the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included three RCTs from the USA; one of these had clinical sites in Germany. Two studies compared emixustat to placebo while the other compared fenretinide to placebo. All assigned one study eye per participant and, combined, have a total of 821 participants with a majority white ethnicity (97.6%). All participants were diagnosed with geographic atrophy due to AMD based on validated imaging modalities. All three studies have high risk of attrition bias mainly due to ocular adverse effects of emixustat and fenretinide. We considered only one study to be adequately conducted and reported with high risk of bias in only one domain (attrition bias). We considered the other two studies to be poorly reported and to have high risk of attrition bias and reporting bias. People with geographic atrophy treated with emixustat may not experience a clinically important change in best-corrected visual acuity (BCVA) between baseline and 24 months compared to people treated with placebo (mean difference (MD) 1.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (CI) -2.34 to 6.14, low-certainty evidence). Emixustat may also result in little or no difference in loss of 15 ETDRS letters or more of BCVA compared with placebo at 24 months (16.4% versus 18%) (risk ratio (RR) 0.91, 95% CI 0.59 to 1.4, low-certainty evidence). In terms of disease progression, emixustat may result in little or no difference in the annual growth rate of geographic atrophy compared with placebo (mean difference MD 0.09 mm/year (95% CI -0.26 to 0.44, low-certainty evidence). All three studies reported adverse events of both drugs (emixustat: moderate-certainty evidence; fenretinide: low-certainty evidence). The main adverse events were ocular in nature and associated with the mechanism of action of the drugs. Delayed dark adaptation (emixustat: 54.5%; fenretinide: 39.3%) and chromatopsia (emixustat: 22.6%; fenretinide: 25.2%) were the most common adverse events reported, and were the most prevalent reasons for study dropout in emixustat trials. These effects were dose-dependent and resolved after drug cessation. No specific systemic adverse events were considered related to emixustat; only pruritus and rash were considered to be due to fenretinide. One emixustat study reported six deaths, none deemed related to the drug. None of the included RCTs reported the other pre-specified outcomes, including proportion of participants losing 10 letters or more, and mean change in macular sensitivity. We planned to investigate progression to advanced AMD (geographic atrophy or neovascular AMD) in prevention studies, including participants with early or intermediate AMD, but we identified no such studies. Two of the included studies reported an additional outcome - incidence of choroidal neovascularisation (CNV) - that was not in our published protocol. CNV onset may be reduced in those treated with emixustat but the evidence was uncertain (risk ratio (RR) 0.67, 95% CI 0.27 to 1.65, low-certainty evidence), or fenretinide (RR 0.5, 95% CI 0.26 to 0.98, low-certainty evidence) compared to placebo. A dose-dependent relationship was observed with emixustat.
AUTHORS' CONCLUSIONS
There is limited evidence to support the use of visual cycle modulators (emixustat and fenretinide) for the treatment of established geographic atrophy due to AMD. The possible reduction in the incidence of CNV observed with fenretinide, and to a lesser extent, emixustat, requires formal assessment in focused studies.
Topics: Aged; Aged, 80 and over; Choroidal Neovascularization; Clinical Trials, Phase II as Topic; Disease Progression; Fenretinide; Geographic Atrophy; Humans; Incidence; Macular Degeneration; Phenyl Ethers; Placebos; Propanolamines; Randomized Controlled Trials as Topic; Visual Acuity; Watchful Waiting
PubMed: 33331670
DOI: 10.1002/14651858.CD013154.pub2