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Investigative Ophthalmology & Visual... Jun 2013The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. (Review)
Review
PURPOSE
The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD.
METHODS
Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies.
RESULTS
TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent.
CONCLUSIONS
Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.
Topics: Aged; Case-Control Studies; Databases, Factual; Diet; Dietary Supplements; Disease Progression; Female; Humans; Macular Degeneration; Male; Middle Aged; Randomized Controlled Trials as Topic; Visual Acuity; Zinc Compounds
PubMed: 23652490
DOI: 10.1167/iovs.12-11552 -
Drug Design, Development and Therapy 2015Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet... (Meta-Analysis)
Meta-Analysis Review
AIMS
Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.
METHODS
A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA), retinal thickness, and lesion size were evaluated.
RESULTS
Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR) group and the intravitreal bevacizumab group (standard mean difference = -0.14, 95% confidence interval [CI] = -0.23 to -0.05). No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN) can raise VA by 1.97 letters (weighted mean difference = 1.97, 95% CI = 0.14-3.794). Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference = 2.74, 95% CI = 0.26-5.21).
CONCLUSION
The superiority remains unclear between IVR and intravitreal bevacizumab in the treatment of neovascular AMD. Intravitreal aflibercept dosed every 2 months required fewer injection times, but produced similar efficacy as monthly IVR. IVR PRN could significantly increase VA. Combined with photodynamic therapy, IVR therapy could also increase VA effectively.
Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Animals; Bevacizumab; Choroidal Neovascularization; Combined Modality Therapy; Humans; Intravitreal Injections; Odds Ratio; Photochemotherapy; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Retina; Signal Transduction; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 26451092
DOI: 10.2147/DDDT.S86269 -
Systematic Reviews Dec 2021The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD.
METHODS
Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters).
RESULTS
After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05-0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05-0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06-0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06-0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0-4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0-4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0-4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0-4.67).
CONCLUSION
The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42015022041.
Topics: Angiogenesis Inhibitors; Humans; Macular Degeneration; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 34930439
DOI: 10.1186/s13643-021-01864-6 -
PloS One 2014Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious... (Meta-Analysis)
Meta-Analysis Review
Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00-1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00-1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44-1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13-1.49) and late AMD (OR, 1.16; 95% CI, 1.11-1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96-1.26), 1.48 (95% CI, 1.44-1.51), and 1.15 (95% CI, 1.11-1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.
Topics: Age Factors; Diabetes Mellitus; Female; Humans; Macular Degeneration; Male; Odds Ratio; Proportional Hazards Models; Risk Factors
PubMed: 25238063
DOI: 10.1371/journal.pone.0108196 -
Annals of Translational Medicine Mar 2022Lutein has been linked with various visual performance disorders, including age-related macular degeneration (AMD). However, previous studies evaluating the association...
BACKGROUND
Lutein has been linked with various visual performance disorders, including age-related macular degeneration (AMD). However, previous studies evaluating the association between serum lutein and the risk of AMD showed results, and the efficacy of lutein intake in AMD patients remains unclear.
METHODS
To comprehensively estimate the relationship between lutein and AMD, a systematic review and meta-analysis was conducted by searching eligible randomized clinical trials (RCT) and case-control studies to study the association between lutein and AMD on the Cochrane Library, MEDLINE, Elsevier, PubMed, Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) databases until April 2020. The weighted mean difference (WMD) with 95% confidence interval (95% CI) was adopted as the primary effect estimate. Meta-analysis was conducted using STATA 12.0.
RESULTS
Nine studies with 855 participants were included in this meta-analysis. The NOS scoring of five case-control studies ranged 5-9. For RCTs, two studies were rated with a low risk of bias, one study with a moderate risk of bias and one with a high risk of bias. The results increased significantly in macular pigment optical density (MPOD) (WMD =0.069; 95% CI: 0.040-0.098, P=0.000) among AMD patients taking lutein supplementation, while there was no difference in circulating lutein levels between AMD patients and controls (WMD =0.00; 95% CI: -0.01 to 0.00, P=0.310). Subgroup analysis suggested that the dose and duration of supplementation could significantly influence the MPOD level in AMD patients. In particular, we observed a larger increase in MPOD of AMD patients using a higher dose (20 mg/d) and longer treatment (>6 months).
CONCLUSIONS
Although current evidence does not support circulating lutein as a biomarker for early screening of the high-risk AMD population, this study is the first meta-analysis to explore the relationship between lutein in blood and AMD patients. Given that lutein has a high safety profile as indicated by many studies, it is reasonable to give the current analysis result that high dose (20 mg/d) and long duration (>6 months) of lutein intake could be beneficial to AMD patients.
PubMed: 35433928
DOI: 10.21037/atm-22-173 -
Stem Cell Research & Therapy Jun 2022Stem cell transplantation may improve visual acuity in patients with dry age-related macular degeneration. Herein, we aimed to summarise the evidence on the risks and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stem cell transplantation may improve visual acuity in patients with dry age-related macular degeneration. Herein, we aimed to summarise the evidence on the risks and benefits of stem cell transplantation for improving visual acuity, including the risk of adverse events.
METHODS
Data were obtained from the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and each database was interrogated from the date of inception until 19 March 2022. The rates of visual acuity outcomes and adverse events associated with stem cell transplantation were examined. All statistical analyses were conducted using Review Manager 5.4. The study was registered with PROSPERO (CRD 42022322902).
RESULTS
The analysis examined 10 studies (102 patients), including one and three, randomised and non-randomised clinical trials, and one and five, multicentre prospective and prospective clinical trials, respectively. Meta-analysis showed changes in best-corrected visual acuity in the study eyes after stem cell transplantation (6 months: risk ratio [RR] = 17.00, 95% confidence interval [CI] 6.08-47.56, P < 0.00001; 12 months: RR = 11.00, 95% CI 2.36-51.36, P = 0.002). Subgroup analysis showed that different stem cell types achieved better best-corrected visual acuity at post-operative 6 months, compared to that observed at baseline. Four cases of related ocular adverse events and no related systemic adverse events were reported.
CONCLUSION
This meta-analysis suggests that stem cell transplantation may improve best-corrected visual acuity in dry age-related macular degeneration, based on small sample sizes and fewer randomised controlled trials.
Topics: Humans; Macular Degeneration; Prospective Studies; Stem Cell Transplantation; Visual Acuity
PubMed: 35672801
DOI: 10.1186/s13287-022-02931-y -
Journal of Clinical Pharmacology May 2022Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment... (Meta-Analysis)
Meta-Analysis Review
Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment burden of frequent intravitreal injections, anti-VEGFs are often used on treat and extend protocols rather than the labeled frequency. The current goal of anti-VEGF drug development is to minimize treatment burden by reducing the number of intravitreal injections. The purpose of this systemic review and model-based meta-analysis (MBMA) was to (1) perform modeling to describe the disease progression of neovascular age-related macular degeneration in the absence of treatment, as well as in the presence of abicipar, aflibercept, brolucizumab, or ranibizumab intervention; (2) and to simulate virtual head-to-head comparisons among the drugs with an extended dose schedule of once every 12 weeks (Q12). Data sources were PubMed, internal Allergan data, www.clinicaltrials.gov, and www.clinicaltrialsregister.eu. Eligibility assessment was performed by 2 independent review authors. Randomized, controlled trials that had at least 1 arm with an anti-VEGF (aflibercept, abicipar, bevacizumab, brolucizumab, pegaptanib, or ranibizumab), a control arm of placebo or anti-VEGF, a treatment duration of at least 4 months, reported best-corrected visual acuity data, and at least 20 patients were included. A total of 22 trials, consisting of 55 arms, from across 9500+ subjects and 500+ best-corrected visual acuity observations were used to develop the model. Consistent with reported data, results from the model showed that abicipar Q12 underperformed ranibizumab (every 4 weeks), aflibercept (every 4 weeks), and brolucizumab (every 8 weeks/Q12) labeled dosing schedules. However, when all drugs were virtually tested using the extended schedule, abicipar outperformed ranibizumab and aflibercept and produced a similar week 52 change from baseline as brolucizumab. Predicted week 52 changes from baseline were 5.92 ± 1.02, 3.04 ± 1.61, 6.61 ± 0.284, and 3.02 ± 2.35 best-corrected visual acuity letters for abicipar, aflibercept, brolucizumab, and ranibizumab, respectively, using the Q12 schedule. Results demonstrate the feasibility of Q12 dosing with clinically meaningful letter gains for abicipar and brolucizumab. The model developed under this MBMA has utility for exploring different regimens for existing or novel anti-VEGF agents.
Topics: Angiogenesis Inhibitors; Disease Progression; Humans; Infant, Newborn; Intravitreal Injections; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Treatment Outcome; Visual Acuity
PubMed: 34783362
DOI: 10.1002/jcph.2002 -
Translational Vision Science &... Nov 2023This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.
RESULTS
Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).
CONCLUSIONS
AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
TRANSLATIONAL RELEVANCE
This systematic review will help to inform and guide future clinical trials.
Topics: Humans; Retinal Degeneration; Dependovirus; Macular Degeneration; Retinitis Pigmentosa; Genetic Therapy
PubMed: 37982768
DOI: 10.1167/tvst.12.11.24 -
Nutrients Nov 2022There is currently no treatment for early/intermediate Age-related Macular Degeneration (AMD) but Eye Care Professionals (ECPs) are recommended to advise patients about... (Review)
Review
What Advice Is Currently Given to Patients with Age-Related Macular Degeneration (AMD) by Eyecare Practitioners, and How Effective Is It at Bringing about a Change in Lifestyle? A Systematic Review.
There is currently no treatment for early/intermediate Age-related Macular Degeneration (AMD) but Eye Care Professionals (ECPs) are recommended to advise patients about modifiable lifestyle factors, including dietary changes, that can slow disease progression. The aim of this review was to understand advice currently given to patients with AMD by ECPs and to evaluate evidence regarding patient compliance. A systematic review was conducted of literature published in electronic databases: CINAHL, MEDLINE, PsycINFO, PyscARTICLES, EMBASE, AMED. Methods followed PRISMA guidelines (PROSPERO registration number: CRD42020223724). Twenty-four reports were eligible for inclusion, 12 focused on ECP experience, 7 on patient experience, and 6 on impact of advice (one paper reported on the ECP and patient experience). Studies reported that a substantial proportion of patients did not recall receiving lifestyle modification advice from their ECP (57.95%, range 2-95% across patient based studies). Practitioners were most likely to provide advice about nutritional supplements (80%, range 67-93% across ECP studies), and least likely about smoking (44%, range 28-71% across ECP studies), however supplements advised did not always comply with evidence-based guidelines. The main reason for patients not following lifestyle advice was lack of provision by the ECP (54.5%, range 21-94% across studies on the impact of advice). The review highlighted a need for more studies to understand patient preferences for receiving advice and research on ECP perceived barriers to advice provision.
Topics: Humans; Macular Degeneration; Dietary Supplements; Life Style; Smoking; Behavior Therapy
PubMed: 36364912
DOI: 10.3390/nu14214652 -
PloS One 2023To evaluate the diagnostic accuracy of deep learning algorithms to identify age-related macular degeneration and to explore factors impacting the results for future... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the diagnostic accuracy of deep learning algorithms to identify age-related macular degeneration and to explore factors impacting the results for future model training.
METHODS
Diagnostic accuracy studies published in PubMed, EMBASE, the Cochrane Library, and ClinicalTrails.gov before 11 August 2022 which employed deep learning for age-related macular degeneration detection were identified and extracted by two independent researchers. Sensitivity analysis, subgroup, and meta-regression were performed by Review Manager 5.4.1, Meta-disc 1.4, and Stata 16.0. The risk of bias was assessed using QUADAS-2. The review was registered (PROSPERO CRD42022352753).
RESULTS
The pooled sensitivity and specificity in this meta-analysis were 94% (P = 0, 95% CI 0.94-0.94, I2 = 99.7%) and 97% (P = 0, 95% CI 0.97-0.97, I2 = 99.6%), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve value were 21.77(95% CI 15.49-30.59), 0.06 (95% CI 0.04-0.09), 342.41 (95% CI 210.31-557.49), and 0.9925, respectively. Meta-regression indicated that types of AMD (P = 0.1882, RDOR = 36.03) and layers of the network (P = 0.4878, RDOR = 0.74) contributed to the heterogeneity.
CONCLUSIONS
Convolutional neural networks are mostly adopted deep learning algorithms in age-related macular degeneration detection. Convolutional neural networks, especially ResNets, are effective in detecting age-related macular degeneration with high diagnostic accuracy. Types of age-related macular degeneration and layers of the network are the two essential factors that impact the model training process. Proper layers of the network will make the model more reliable. More datasets established by new diagnostic methods will be used to train deep learning models in the future, which will benefit for fundus application screening, long-range medical treatment, and reducing the workload of physicians.
Topics: Humans; Deep Learning; Neural Networks, Computer; Algorithms; Macular Degeneration; Sensitivity and Specificity; Diagnostic Tests, Routine
PubMed: 37023082
DOI: 10.1371/journal.pone.0284060