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Ophthalmology. Retina Jun 2024To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD). (Meta-Analysis)
Meta-Analysis Review
TOPIC
To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD).
CLINICAL RELEVANCE
Among > 100 OCT prognostic biomarkers for AMD, it is unclear which are the most relevant for clinicians and researchers to focus on. This review evaluated which OCT biomarkers confer the greatest magnitude of prediction for progression to late AMD.
METHODS
Study protocol was registered on PROSPERO (CRD42023400166). PubMed and Embase were searched from inception to March 2, 2023, and eligible studies assessed following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was any quantified risk of progression from treatment-naive early/intermediate AMD to late AMD, including hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (at baseline, between eyes with versus without progression), subgrouped by each OCT biomarker. Further meta-analyses were subgrouped by progression to geographic atrophy or neovascularization.
RESULTS
A total of 114 quantified OCT prognostic biomarkers were identified. With high GRADE certainty of evidence, the greatest magnitudes of prediction to late AMD belonged to: external limiting membrane abnormality (OR, 15.42 [7.63, 31.17]), ellipsoid zone abnormality (OR, 10.8 [4.58, 25.46]), interdigitation zone abnormality (OR, 7.68 [2.57, 23]), concurrent large drusen and reticular pseudodrusen (HR, 6.73 [1.35, 33.65], hyporeflective drusen cores (HR, 2.48 [1.8, 3.4]; OR 1.85 [1.29, 2.66]), intraretinal hyperreflective foci (IHRF; HR, 2.16 [0.92, 5.07]; OR 5.08 [3.26, 7.92]), and large drusen (HR, 2.01 [1.35, 2.99]); OR, 1.98 [1.27, 3.08]). There was greater risk of geographic atrophy for IHRF and hyporeflective drusen cores (P < 0.05), and neovascularization for ellipsoid zone abnormality (P < 0.05). Other OCT biomarkers such as drusenoid pigment epithelium detachment, shallow irregular retinal pigment epithelium elevations, and nascent geographic atrophy exhibited large magnitudes of risk but required further studies for validation.
CONCLUSION
This review synthesizes the 6 most relevant OCT prognostic biomarkers for AMD with greater predictive ability than large drusen alone, for clinicians and researchers to focus on. Further study is required to validate other biomarkers with less than high certainty of evidence, and assess how the copresence of biomarkers may affect risks.
FINANCIAL DISCLOSURE(S)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Topics: Humans; Disease Progression; Prognosis; Tomography, Optical Coherence; Biomarkers; Macular Degeneration
PubMed: 38154619
DOI: 10.1016/j.oret.2023.12.006 -
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 -
Acta Ophthalmologica Feb 2024Optic disc drusen (ODD) are calcium-containing deposits in the optic nerve head, capable of causing visual field defects and sudden visual loss. The underlying... (Meta-Analysis)
Meta-Analysis Review
Optic disc drusen (ODD) are calcium-containing deposits in the optic nerve head, capable of causing visual field defects and sudden visual loss. The underlying pathophysiology remains inadequately understood and treatment options are missing. In this paper, we systematically reviewed prevalence studies of ODD in non-selected populations to provide an overview of its prevalence, conducted meta-analyses to determine modality-specific prevalence estimates and performed a forecasting study to estimate current and future global population number of individuals with ODD. We searched 11 literature databases on 25 October 2022 for prevalence studies of ODD in non-selected populations. Eight eligible studies provided data from a total of 27 463 individuals. Prevalence estimates were stratified according to diagnostic modalities: ophthalmoscopy 0.37% (95% CI: 0.10-0.95%), fundus photography 0.12% (95% CI: 0.03-0.24%), spectral domain optical coherence tomography with enhanced depth imaging 2.21% (95% CI: 1.25-3.42%) and histopathology 1.82% (95% CI: 1.32-2.38%). Using histopathology-based summary prevalence estimate, we forecast 145 million individuals with ODD currently, a number expected to increase further due to world population growth. These numbers underscore the importance of including ODD in health education and highlight the necessity of continuing research in ODD.
Topics: Humans; Optic Disk; Optic Disk Drusen; Prevalence; Tomography, Optical Coherence
PubMed: 37144704
DOI: 10.1111/aos.15690 -
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 -
Retina (Philadelphia, Pa.) Aug 2022To survey the current literature regarding applications of deep learning to optical coherence tomography in age-related macular degeneration (AMD).
PURPOSE
To survey the current literature regarding applications of deep learning to optical coherence tomography in age-related macular degeneration (AMD).
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review was conducted from January 1, 2000, to May 9, 2021, using PubMed and EMBASE databases. Original research investigations that applied deep learning to optical coherence tomography in patients with AMD or features of AMD (choroidal neovascularization, geographic atrophy, and drusen) were included. Summary statements, data set characteristics, and performance metrics were extracted from included articles for analysis.
RESULTS
We identified 95 articles for this review. The majority of articles fell into one of six categories: 1) classification of AMD or AMD biomarkers (n = 40); 2) segmentation of AMD biomarkers (n = 20); 3) segmentation of retinal layers or the choroid in patients with AMD (n = 7); 4) assessing treatment response and disease progression (n = 13); 5) predicting visual function (n = 6); and 6) determining the need for referral to a retina specialist (n = 3).
CONCLUSION
Deep learning models generally achieved high performance, at times comparable with that of specialists. However, external validation and experimental parameters enabling reproducibility were often limited. Prospective studies that demonstrate generalizability and clinical utility of these models are needed.
Topics: Deep Learning; Humans; Macular Degeneration; Prospective Studies; Reproducibility of Results; Retinal Drusen; Tomography, Optical Coherence
PubMed: 35877964
DOI: 10.1097/IAE.0000000000003535 -
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 -
Retina (Philadelphia, Pa.) Dec 2021Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the... (Meta-Analysis)
Meta-Analysis
GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.
PURPOSE
Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration.
METHODS
Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy.
RESULTS
Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21-1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen.
CONCLUSION
We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.
Topics: Aged; Angiogenesis Inhibitors; Bevacizumab; Choroidal Neovascularization; Disease Progression; Female; Follow-Up Studies; Geographic Atrophy; Humans; Incidence; Intravitreal Injections; Male; Middle Aged; Prevalence; Ranibizumab; Risk Factors; Vascular Endothelial Growth Factor A; Wet Macular Degeneration
PubMed: 34101693
DOI: 10.1097/IAE.0000000000003207 -
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