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The Cochrane Database of Systematic... Jun 2023Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line).
OBJECTIVES
The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months).
SEARCH METHODS
We searched various electronic databases on 8 July 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence.
MAIN RESULTS
We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs.
AUTHORS' CONCLUSIONS
There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants.
Topics: Humans; Ranibizumab; Bevacizumab; Macular Edema; Diabetic Retinopathy; Endothelial Growth Factors; Vascular Endothelial Growth Factor A; Network Meta-Analysis; Laser Coagulation; Diabetes Mellitus
PubMed: 38275741
DOI: 10.1002/14651858.CD007419.pub7 -
Journal of Clinical Medicine Jan 2024: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood... (Review)
Review
: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. : We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. : A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. : Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed.
PubMed: 38256501
DOI: 10.3390/jcm13020367 -
Cureus Dec 2023Circumscribed choroidal hemangioma (CCH) is a sort of non-malignant hamartomatous tumor that occurs in the choroidal layer of the eye. It is a rare condition that... (Review)
Review
Circumscribed choroidal hemangioma (CCH) is a sort of non-malignant hamartomatous tumor that occurs in the choroidal layer of the eye. It is a rare condition that affects people between their second and fourth decades of life, leading to significant deterioration of vision. One of the most catastrophic consequences of CCH is exudative retinal detachment (ERD), which has a severe impact on vision. This review aims to comprehensively assess the safety and efficacy of photodynamic therapy (PDT) using verteporfin as a therapeutic approach. Using the eligibility criteria, we analyzed the findings of 18 published articles from PubMed, Web of Science, Scopus, and Cochrane. The standard PDT protocol was used in all included studies, except two (one used half-dose, the other one used the double-dose) with an average of 1-2 sessions. PDT induced substantial tumor regression, with a mean thickness range from 0 to 2.3 mm. However, this contrasted with a previous study that reported a thickness of 3.46 mm as an indication of PDT failure. The mean tumor diameter varied from 4.8 mm to total tumor flattening. A suboptimal effect with a mean diameter ranging from 6mm to 8mm was found in two clinical studies. Significant improvement in vision was observed during the last follow-up, ranging from a normalization of Best Corrected Visual Acuity (BCVA) 20/20 to 20/80; counting finger vision persisted in two patients even after treatment. PDT successfully achieved complete subretinal fluid (SRF) resolution in 14 studies and resolved ERD in nine articles. Most studies did not report serious adverse events, but some reported macular atrophy, microcystic degeneration of the retina, transient visual disturbances, Retinal pigmented epithelium (RPE) metaplasia, and cystic degeneration of the retina. This systemic review demonstrated PDT's effectiveness and safety as a first-line management modality for CCH. Photodynamic therapy efficiently induced tumor regression, resulting in a notable reduction in both tumor diameter and thickness, with optimal efficacy to improve vision and resolution of the consequences of CCH, such as SRF and ERD.
PubMed: 38222120
DOI: 10.7759/cureus.50461 -
Medicine Dec 2023A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.
INTRODUCTION
A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME).
MATERIALS AND METHODS
A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies.
RESULTS
A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events.
CONCLUSIONS
Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.
Topics: Antibodies, Bispecific; Vascular Endothelial Growth Factor A; Macular Degeneration; Humans; Randomized Controlled Trials as Topic; Macular Edema; Diabetes Complications; Treatment Outcome
PubMed: 38115358
DOI: 10.1097/MD.0000000000036370 -
BMC Ophthalmology Dec 2023Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based potential biomarkers of AMD that contribute to understanding the mechanisms of disease and aiding in early diagnosis.
METHODS
This study retrieved studies that aim to detect differences relate to proteomics in AMD patients and healthy control groups by mass spectrometry (MS) proteomics approaches. The search process was accord with PRISMA guidelines (PROSPERO database: CRD42023388093). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes Pathway Analysis (KEGG) were performed on differentially expressed proteins (DEPs) in the included articles using the DAVID database. DEPs were included in a meta-analysis when their effect size could be computed in at least two research studies. The effect size of measured proteins was transformed to the log2-fold change. Protein‒protein interaction (PPI) analysis was conducted on proteins that were statistically significant in the meta-analysis using the String online database.
RESULTS
Eleven studies fulfilled the inclusion criteria, and 161 DEPs were identified. The GO analysis showed that AMD is significantly related to proteolysis, extracellular exosome and protein binding. In KEGG, the most significant pathway was the complement and coagulation cascades. Meta-analysis results suggested that eight proteins were statistically significant, and according to PPI results, the most significant four proteins were serotransferrin (TF), apolipoprotein A1 (APOA1), complement C3 (C3) and lipocalin-1 (LCN1).
CONCLUSIONS
Four possible biomarkers, TF, APOA1, C3 and LCN1, were found to be significant in the pathogenesis of AMD and need to be further validated. Further studies should be performed to evaluate diagnostic and therapeutic value of these proteins.
Topics: Humans; Proteomics; Macular Degeneration; Biomarkers; Proteins; Mass Spectrometry
PubMed: 38087257
DOI: 10.1186/s12886-023-03237-0 -
BMC Ophthalmology Nov 2023Age-related Macular Degeneration (AMD) is one of the most common causes of vision loss. A substantial increase in the burden of AMD is expected in the aging populations,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related Macular Degeneration (AMD) is one of the most common causes of vision loss. A substantial increase in the burden of AMD is expected in the aging populations, including the Iranians. We investigated the age and gender-specific prevalence of AMD and its determinants in Iran.
METHODS
We systematically searched international (PubMed, Scopus, Embase, etc.) and local (IranDoc, Magiran, etc.) online databases. We included cross-sectional or cohort studies, either clinic- or population-based, published on the prevalence of AMD among Iranians, with no limitation on age. Joanna Briggs Institute (JBI) tools for critical appraisal were used. Prevalence estimates are pooled by applying random-effects modeling. Subgroup analysis and meta-regression were performed.
RESULTS
Seventeen studies with 16,120 participants were included. Based on studies in general population, the pooled prevalence of AMD was 10.8% (95% CI: 6.5-16.2%) in males, and 9.8% (95% CI: 4.7-16.4%) in females. 8.5% of moderate vision impaired, 13.6% of severe vision impaired, and 15.7% of blind participants were affected by AMD. The prevalence of AMD was 2% in 40-49, and 32.3% in the ≥ 80 population. The prevalence of AMD was 11.9% among the visually impaired vs. 8.7% in the general population. The study's sampling method, location, and mean age were correlated with the heterogeneities of the prevalence. We observed an increasing trend in the number of AMD cases (average annual percent change = 3.66%; 95% CI: 3.65-3.67%) from 1990 to 2050. The expected number of AMD cases in Iran will be near 5.5 million by 2050.
CONCLUSION
The prevalence of AMD in Iran was somewhere between the prevalence of Asians and Europeans. Given the aging trend of the Iranian community and an average annual percent change of 3.66%, it is indispensable to adopt preventive and screening policies to diminish the burden of the disease in the future decades.
Topics: Male; Female; Humans; Iran; Prevalence; Cross-Sectional Studies; Macular Degeneration; Blindness
PubMed: 38007475
DOI: 10.1186/s12886-023-03218-3 -
BMC Ophthalmology Nov 2023To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.
OBJECTIVES
To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED).
METHODS
Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022.
RESULTS
One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58.
CONCLUSIONS
IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Retinal Detachment; Network Meta-Analysis; Vascular Endothelial Growth Factor A; Retinal Pigment Epithelium; Retrospective Studies; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Intravitreal Injections; Macular Degeneration
PubMed: 37990182
DOI: 10.1186/s12886-023-03214-7 -
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 -
PloS One 2023Age-related macular degeneration (AMD) is an eye disease that occurs in patients over 50 years old. Early diagnosis enables timely treatment to stabilize disease...
INTRODUCTION
Age-related macular degeneration (AMD) is an eye disease that occurs in patients over 50 years old. Early diagnosis enables timely treatment to stabilize disease progression. However, the fact that the disease is asymptomatic in its early stages can delay treatment until it progresses. As such, screening in specific contexts can be an early detection tool to reduce the clinical and social impact of the disease.
OBJECTIVE
Assess the effectiveness of screening methods for early detection of AMD in adults aged 50 years or older.
METHODS
A systematic review of comparative observational studies on AMD screening methods in those aged 50 years or older, compared with no screening or any other strategy. A literature search was conducted in the MEDLINE (via PubMed), Embase, Cochrane Library and Lilacs database.
RESULTS
A total of 5,290 studies were identified, three of which met the inclusion criteria and were selected for the systematic review. A total of 8,733 individuals (16,780 eyes) were included in the analysis. The screening methods assessed were based on optical coherence tomography (OCT) compared with color fundus photography, and OCT and telemedicine testing compared to a standard eye exam.
CONCLUSION
The systematized data are limited and only suggest satisfactory performance in early screening of the population at risk of developing AMD. OCT and the telemedicine technique showed promising results in AMD screening. However, methodological problems were identified in the studies selected and the level of evidence was considered low.
Topics: Humans; Middle Aged; Macular Degeneration; Tomography, Optical Coherence; Treatment Outcome; Diagnostic Techniques, Ophthalmological; Photography
PubMed: 37971992
DOI: 10.1371/journal.pone.0294398 -
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