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Survey of Ophthalmology 2024There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently,... (Meta-Analysis)
Meta-Analysis Review
There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future.
Topics: Humans; Prognosis; Angiogenesis Inhibitors; Disease Progression; Visual Acuity; Vascular Endothelial Growth Factor A; Wet Macular Degeneration; Retinal Drusen
PubMed: 37890677
DOI: 10.1016/j.survophthal.2023.10.010 -
Eye (London, England) Aug 2023The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease... (Review)
Review
UNLABELLED
The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease progression and response to treatment in neovascular age-related macular degeneration (nAMD) and (2) establish which biomarkers are currently identifiable by artificial intelligence (AI) models and the utilisation of this technology. Following the PRISMA guidelines, PubMed was searched for peer-reviewed publications dated between January 2016 and January 2022.
POPULATION
Patients diagnosed with nAMD with OCT imaging.
SETTINGS
Comparable settings to NHS hospitals.
STUDY DESIGNS
Randomised controlled trials, prospective/retrospective cohort studies and review articles. From 228 articles, 130 were full-text reviewed, 50 were removed for falling outside the scope of this review with 10 added from the author's inventory, resulting in the inclusion of 90 articles. From 9 biomarkers identified; intraretinal fluid (IRF), subretinal fluid, pigment epithelial detachment, subretinal hyperreflective material (SHRM), retinal pigmental epithelial (RPE) atrophy, drusen, outer retinal tabulation (ORT), hyperreflective foci (HF) and retinal thickness, 5 are considered pertinent to nAMD disease progression; IRF, SHRM, drusen, ORT and HF. A number of these biomarkers can be classified using current AI models. Significant retinal biomarkers pertinent to disease activity and progression in nAMD are identifiable via OCT; IRF being the most important in terms of the significant impact on visual outcome. Incorporating AI into ophthalmology practice is a promising advancement towards automated and reproducible analyses of OCT data with the ability to diagnose disease and predict future disease conversion.
SYSTEMATIC REVIEW REGISTRATION
This review has been registered with PROSPERO (registration ID: CRD42021233200).
Topics: Humans; Tomography, Optical Coherence; Artificial Intelligence; Retrospective Studies; Prospective Studies; Fluorescein Angiography; Biomarkers; Macular Degeneration; Disease Progression; Wet Macular Degeneration; Angiogenesis Inhibitors
PubMed: 36526863
DOI: 10.1038/s41433-022-02360-4 -
Nutrients May 2022Age-related macular degeneration (AMD) is a serious degenerative disease affecting the eyes, and is the main cause of severe vision loss among people >55 years of age in... (Review)
Review
Age-related macular degeneration (AMD) is a serious degenerative disease affecting the eyes, and is the main cause of severe vision loss among people >55 years of age in developed countries. Its onset and progression have been associated with several genetic and lifestyle factors, with diet appearing to play a pivotal role in the latter. In particular, dietary eating patterns rich in plant foods have been shown to lower the risk of developing the disease, and to decrease the odds of progressing to more advanced stages in individuals already burdened with early AMD. We systematically reviewed the literature to analyse the relationship between the adherence to a Mediterranean diet, a mainly plant-based dietary pattern, and the onset/progression of AMD. Eight human observational studies were analysed. Despite some differences, they consistently indicate that higher adherence to a Mediterranean eating pattern lowers the odds of developing AMD and decreases the risk of progression to more advanced stages of the disease, establishing the way for preventative measures emphasizing dietary patterns rich in plant-foods.
Topics: Diet, Mediterranean; Eye; Feeding Behavior; Humans; Life Style; Macular Degeneration; Middle Aged
PubMed: 35631175
DOI: 10.3390/nu14102028 -
Clinical Ophthalmology (Auckland, N.Z.) 2021Geographic atrophy (GA), the advanced form of dry age-related macular degeneration, can result in irreversible blindness over time. We performed a systematic literature... (Review)
Review
PURPOSE
Geographic atrophy (GA), the advanced form of dry age-related macular degeneration, can result in irreversible blindness over time. We performed a systematic literature review to assess the humanistic and economic burden of GA.
METHODS
Predefined search terms were used to identify studies in PubMed, Embase, and Cochrane Library; conference abstracts also were searched.
RESULTS
Of 1111 unique studies identified, 25 studies on humanistic burden, 4 on economic burden, and 3 on both humanistic and economic burden of GA were included. Vision-related functioning and health-related quality of life (HRQOL) are poor in patients with GA. HRQOL is commonly measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25); patients with GA have significantly lower composite and subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision than individuals without GA. Driving is a particular concern, and inability to drive affects dependency. Vision-related quality of life (VRQOL) declines as GA progresses. While we identified only 7 reports describing the economic burden of GA, its direct costs may be substantial. In a US study, mean cost to the payer per patient with GA was $11,533 in the year after diagnosis. A multinational study estimated annualized total direct costs of €1772 per patient with GA, mainly driven by diagnostic tests and procedures (€1071). Patients with GA are at increased risk of falls and fractures, potentially increasing direct costs. Only one study evaluated indirect costs, estimating ~$24.4 billion in yearly lost wages among people with severe vision loss due to GA or drusen ≥125 μm.
CONCLUSION
GA represents a significant humanistic burden. Evidence on the economic impact of GA is limited; characterizing the economic burden of GA requires further research. Interventions that reduce GA-related disability may improve HRQOL and reduce indirect costs.
PubMed: 34916775
DOI: 10.2147/OPTH.S338253 -
The Cochrane Database of Systematic... May 2021Age-related macular degeneration (AMD) is one of the leading causes of blindness in high-income countries. The majority of cases of AMD are of the non-exudative type.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is one of the leading causes of blindness in high-income countries. The majority of cases of AMD are of the non-exudative type. Experts have proposed photobiomodulation (PBM) therapy as a non-invasive procedure to restore mitochondrial function, upregulate cytoprotective factors and prevent apoptotic cell death in retinal tissue affected by AMD.
OBJECTIVES
To assess the effectiveness and safety of PBM compared to standard care, no treatment or sham treatment for people with non-exudative AMD.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 5, 2020), Ovid MEDLINE, Embase, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to 11 May 2020 with no language restrictions.
SELECTION CRITERIA
The review included randomised controlled trials (RCTs) on participants receiving any type of PBM therapy for non-exudative AMD compared to standard care, sham treatment or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We considered the following outcome measures at 12 months: best-corrected visual acuity (BCVA) ; contrast sensitivity; near vision; low luminance density score; reading speed; vision-related quality of life score; and adverse events such as progression of AMD and conversion to exudative AMD. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included two published RCTs from single centres in the UK and Canada, which recruited 60 participants (60 eyes) and 30 participants (46 eyes) respectively. Participants in these trials were people with non-exudative AMD with Age-Related Eye Disease Study (AREDS) categories 2 to 4. One study compared single wavelength PBM with no treatment. This study was at risk of performance bias because the study was not masked, and there was attrition bias. One study compared multi-wavelength PBM with sham treatment and conflicts of interest were reported by study investigators. We also identified three eligible ongoing RCTs from searching the clinical trials database. When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in BCVA at 12 months (mean difference (MD) 0.02 logMAR, 95% confidence interval (CI) -0.02 to 0.05; 2 RCTs, 90 eyes; low-certainty evidence). One study comparing multi-wavelength PBM with sham treatment showed an improvement in contrast sensitivity at Level E (18 cycles/degree) at 12 months (MD 0.29 LogCS, 95% CI 0.23 to 0.35; 1 RCT, 46 eyes; low-certainty evidence). Visual function and health-related quality of life scores were comparable between single wavelength PBM and no treatment groups at 12 months (VFQ-48 score MD 0.43, 95% CI -0.17 to 1.03; P = 0.16; 1 RCT, 47 eyes; low-certainty evidence). When comparing PBM with sham treatment or no treatment for non-exudative AMD, there was no evidence of any meaningful clinical difference in conversion to exudative AMD (risk ratio (RR) 0.97, 95% CI 0.17 to 5.44; 2 RCTs, 96 eyes; very low-certainty evidence) at 12 months. There was inconclusive evidence that single wavelength PBM prevents the progression of AMD (RR 0.79, 95% CI 0.41 to 1.53; P = 0.48; 1 RCT, 50 eyes; low-certainty evidence). Disease progression was defined as the development of advanced AMD or significant increase in drusen volume. No included study reported near vision, low luminance vision or reading speed outcomes.
AUTHORS' CONCLUSIONS
Currently there remains uncertainty whether PBM treatment is beneficial in slowing progression of non-exudative macular degeneration. There is a need for further well-designed controlled trials assessing dosimetry, powered for both effectiveness and safety outcomes. Consideration should be given to the adoption of agreed clinical outcome measures and patient-based outcome measures for AMD.
Topics: Bias; Confidence Intervals; Contrast Sensitivity; Disease Progression; Humans; Low-Level Light Therapy; Macular Degeneration; Outcome Assessment, Health Care; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Visual Acuity
PubMed: 34097768
DOI: 10.1002/14651858.CD013029.pub2 -
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 -
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 -
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