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Nutrients Oct 2022: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if... (Meta-Analysis)
Meta-Analysis Review
: Age-related macular degeneration (AMD) is a neurodegenerative ophthalmic disease. The purpose of this systematic review (SR) and meta-analysis was to evaluate if dietary supplementation alone or in combinations might delay the progression of any of the stages of AMD. A SR and meta-analysis identifying cohort studies and randomized controlled trials (RCTs) evaluating the effect of supplements in patients diagnosed with AMD. PubMed, Scopus, Web of Science, CINAHL, and Cochrane were searched through 8th October 2021. Twenty studies, examining 5634 participants ranging from 55 to 80 years, were included in the SR. Eight studies were selected for meta-analysis (414 and 216 subjects in the intervention and control groups). Lutein and zeaxanthin plus -3 long-chain polyunsaturated fatty acids (-3 LC-PUFA) supplementation showed significant improvements in best-corrected visual acuity (BCVA) (SMD: -1.99, 95% CI: -3.33, -0.65) compared to the control group. Multifocal electroretinogram results (mfERG) were significantly improved overall (SMD: 4.59, 95% CI: 1.75, 7.43) after lutein plus zeaxanthin supplementation. Combinations of lutein and zeaxanthin with -3 LC-PUFA might be beneficial in preventing AMD progression and deterioration of visual function. Our results encourage initiating further studies with combinations of -3 LC-PUFA, lutein, and zeaxanthin especially in early AMD patients.
Topics: Humans; Zeaxanthins; Lutein; Xanthophylls; Visual Acuity; Double-Blind Method; Macular Degeneration; Dietary Supplements; Fatty Acids, Omega-3
PubMed: 36296956
DOI: 10.3390/nu14204273 -
Ophthalmology and Therapy Oct 2023Clinical trials in neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor (ant-VEGF) injections use disease activity (DA)... (Review)
Review
Systematic Review of Neovascular Age-Related Macular Degeneration Disease Activity Criteria Use to Shorten, Maintain or Extend Treatment Intervals with Anti-VEGF in Clinical Trials: Implications for Clinical Practice.
INTRODUCTION
Clinical trials in neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor (ant-VEGF) injections use disease activity (DA) criteria to shorten, maintain or increase the interval between injections. Differences in these DA criteria may contribute to differences in the proportions of patients with macular fluid at key time points or achieving extended dosing intervals in these trials. We identified, collated and evaluated DA criteria from pivotal anti-VEGF nAMD trials to understand how differences impact on these studies and real-world visual acuity and extending dosing outcomes.
METHODS
This was a systematic review of literature on Pubmed for randomised clinical trials in nAMD using a proactive treatment regimen. We excluded case reports, review articles and studies on fewer than 50 participants.
RESULTS
Twelve clinical trials (LUCAS, VIEW, TREX-AMD, FLUID, TREND, RIVAL, ALTAIR, CANTREAT, ARIES, TREX-Conbercept, HAWK & HARRIER, TENAYA & LUCERNE) investigating anti-VEGF treatment of nAMD were identified according to our search strategy. Different studies utilised a different combination of DA criteria. Specifically, six trials included visual acuity change; four included macular thickness change; one included visual acuity change if associated with macular thickness change; one with qualitative optical coherence tomography (OCT) features; four with qualitative OCT features if also associated with visual acuity change; 10 with macular haemorrhage and five with other fluorescein angiographic features.
CONCLUSION
Different clinical trials use different DA criteria when altering the interval between anti-VEGF injections. This makes it difficult to draw meaningful conclusions about secondary outcomes such as proportion of patients treated at extended dosing intervals or proportions of eyes with persistent subretinal or intraretinal fluid. Standardising DA criteria in clinical trials and preferentially using those easily applied in a real-world setting would lead to results more achievable in real-world settings and for a meaningful comparison of treatment durability.
PubMed: 37477856
DOI: 10.1007/s40123-023-00768-z -
American Journal of Ophthalmology Feb 2023To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD).
DESIGN
Systematic review and meta-analysis.
METHODS
The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included.
RESULTS
Identification of fibrosis is challenging. Optical coherence tomography angiography and polarization-sensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (-26.86 letters).
CONCLUSIONS
There is a need to identify effective treatment strategies for fibrosis and to closely monitor at-risk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis.
Topics: Humans; Angiogenesis Inhibitors; Retina; Choroidal Neovascularization; Fibrosis; Tomography, Optical Coherence; Macular Degeneration; Fluorescein Angiography; Intravitreal Injections; Wet Macular Degeneration
PubMed: 36162537
DOI: 10.1016/j.ajo.2022.09.008 -
Disability and Rehabilitation Mar 2022The aim of this meta-synthesis is to find out what it means for patients with age-related macular degeneration to live with visual impairment, how they cope with the...
AIM
The aim of this meta-synthesis is to find out what it means for patients with age-related macular degeneration to live with visual impairment, how they cope with the illness and how they experience their medical care, including vascular endothelial growth factor inhibitor therapy.
METHOD
Inclusion criteria: qualitative studies exploring patients' experiences with age-related macular degeneration in their daily lives and with medical care, published in journals in English or German. The included studies were analysed following the rules and principles of grounded theory.
RESULTS
For the analysis, twenty-four articles matching the inclusion criteria were identified. Three main analytic themes emerged from the included studies: (i) a life shaped by losses; (ii) the burden of medical treatment; and (iii) coping with vision loss. For patients, visual impairment/vision loss means living with multiple losses in various domains of life. With the introduction of vascular endothelial growth factor inhibitor therapy, patients with neovascular age-related macular degeneration have a good chance of slowing down the disease progression; therapy does, however, also represent a major burden.
CONCLUSION
New strategies need to be conceived to reduce the burden of medical treatment and to improve the dissemination of information about age-related macular degeneration.IMPLICATIONS FOR REHABILITATIONMost of the people with age- related macular degeneration seem to adapt to visual impairment.Medical treatment implies a great physical and psychological burden for patients with neovascular (wet) age- related macular degeneration.The physical and psychological burden needs to be recognized and addressed in the management of patients with neovascular (wet) AMD in medical facilities.More research is needed on how rehabilitation services may support the adaptation process of patients in the different stages of AMD.
Topics: Adaptation, Psychological; Angiogenesis Inhibitors; Humans; Quality of Life; Vascular Endothelial Growth Factor A; Vision, Low; Wet Macular Degeneration
PubMed: 32574120
DOI: 10.1080/09638288.2020.1775901 -
Ophthalmology and Therapy Jun 2021Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes.... (Review)
Review
BACKGROUND
Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes. Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients. Recent studies indicate a potential role for metformin in delaying AMD development and progression. In this context, we conducted a systematic review and meta-analysis to look for beneficial associations between metformin and AMD.
METHODS
We systematically searched Medline and Embase (via Ovid), Web of Science, and ClinicalTrials.gov databases for clinical studies in humans that examined the associations between metformin treatment and AMD published from inception to February 2021. We calculated pooled odds ratio (OR) with 95% confidence interval (CI) considering a random effect model in the meta-analysis.
RESULTS
Five retrospective studies met the inclusion criteria. There are no prospective studies that have reported the effect of metformin in AMD. The meta-analysis showed that people taking metformin were less likely to have AMD although statistical significance was not met (pooled adjusted OR = 0.80, 95% CI 0.54-1.05, I = 98.8%). Subgroup analysis of the association between metformin and early and late AMD could not be performed since the data was not available from the included studies.
CONCLUSIONS
Analysis of retrospective data suggests a signal that metformin may be associated with decreased risk of any AMD. It should be interpreted with caution because of the failure to meet statistical significance, the small number of studies, and the limitation of routine record data. However prospective studies are warranted in generalizable populations without diabetes, of varied ethnicities, and AMD stages. Clinical trials are needed to determine if metformin has efficacy in treating early and late-stage AMD.
PubMed: 33846958
DOI: 10.1007/s40123-021-00344-3 -
Scientific Reports Jan 2024We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Bispecific; Intravitreal Injections; Macular Degeneration
PubMed: 38291069
DOI: 10.1038/s41598-024-52942-3 -
The British Journal of Ophthalmology Oct 2021We performed a systematic review and meta-analysis to summarise the geographic distribution of age-related macular degeneration (AMD) incidence. (Meta-Analysis)
Meta-Analysis
PURPOSE
We performed a systematic review and meta-analysis to summarise the geographic distribution of age-related macular degeneration (AMD) incidence.
METHODS
Databases including PubMed, Embase and Web of Science were searched for publications of early and late AMD before September 2019. Studies were included if they applied a standardised photographic assessment and classification system. The proportion of participants with AMD in each eligible study was combined to obtain a pooled incidence from all studies using a random effects model. We also assessed sources of potential heterogeneity in the incidence of AMD using meta-regression analyses for both late and early AMD.
RESULTS
Twenty-four population-based studies (70 123 individuals aged 55 years or older) were included in the meta-analysis. The pooled global annual incidences of early and late AMD were 1.59% (95% CI 1.12% to 2.10%) and 0.19% (95% CI: 0.13% to 0.28%), respectively. Individuals of European descent had the highest annual incidence of both early (2.73%, 95% CI 1.63% to 4.57%) and late (0.36%, 95% CI 0.17% to 0.75%) AMD than other ethnic groups. Average age (p=0.001) at baseline, ethnicity (p=0.001), region (p=0.043) and gender (p=0.011) were predictors for incident late AMD, while only average age (p=0.01) at baseline and ethnicity (p=0.025) was associated with incidence of early AMD.
CONCLUSIONS
This meta-analysis offers an up-to-date overview of AMD globally, which may provide scientific guidance for the design and implementation of public health strategies such as screening programmes for AMD in both specific geographic locations and ethnic groups, as well as worldwide.
Topics: Databases, Factual; Ethnicity; Humans; Incidence; Macular Degeneration; Risk Factors
PubMed: 32907810
DOI: 10.1136/bjophthalmol-2020-316820 -
Life (Basel, Switzerland) Mar 2023Recalcitrant neovascular age-related macular degeneration (rnAMD) despite intensive intravitreal anti-neovascular endothelial growth factor (VEGF) treatment, can be... (Review)
Review
BACKGROUND
Recalcitrant neovascular age-related macular degeneration (rnAMD) despite intensive intravitreal anti-neovascular endothelial growth factor (VEGF) treatment, can be handled by switching to another anti-VEGF agent. This first systematic review and meta-analysis presents long-term data after switching from another anti-VEGF agent to brolucizumab.
METHODS
Retrospective case series over two years of patients switched to brolucizumab, and a systematic review and meta-analysis of peer-reviewed studies presenting patients switched to brolucizumab. Weighted mean differences based on the random-effects models were calculated for best-corrected visual acuity (BCVA) and central subfield thickness (CST).
RESULTS
The systematic review draws on 1200 eyes switched to brolucizumab. The meta-analysis showed a clinically irrelevant decrease in BCVA after one and two months, together with significant decreases in CST for up to one year after the switch but lacking power over 2 years. Of twelve eyes (twelve patients) in our case series, five continued treatment for two years without experiencing significant changes.
CONCLUSIONS
After switch to brolucizumab, a significant morphological improvement with CST reduction was shown in eyes with rnAMD. The small worsening of BCVA may be owing to the chronically active nature of rnAMD. Brolucizumab thus remains a treatment option in rnAMD despite its potential side effects.
PubMed: 36983970
DOI: 10.3390/life13030814 -
Acta Ophthalmologica Jun 2021The aim of the present systematic review was to assess the association between age-related macular degeneration (AMD) and periodontal and peri-implant diseases. The...
The aim of the present systematic review was to assess the association between age-related macular degeneration (AMD) and periodontal and peri-implant diseases. The focused question was 'Is there a relationship between AMD and periodontal and peri-implant diseases?' Indexed databases were searched up to and including May 2020 to identify pertinent original studies. The Cochrane Collaboration's tool was used to assess the risk of bias. Five observational cohort studies were included that assessed the association between AMD and periodontitis. The number of patients with and without AMD ranged between 54 and 90 and 1697 and 12,171 individuals, respectively. Examiner blinding to the study groups was performed in 1 of the 5 studies. None of the studies were power adjusted. Scrutiny of studies showed that all 5 studies included in the present systematic review had a high risk of bias. Results from all studies reported a direct association between AMD and periodontitis. No studies assessed the association between AMD and peri-implant diseases. The association between AMD and periodontal and peri-implant diseases remains debatable. Further well-designed and power-adjusted studies are needed to determine whether or not a 'true' association exists between AMD and periodontal and peri-implant diseases.
Topics: Humans; Macular Degeneration; Peri-Implantitis; Periodontitis; Risk Factors
PubMed: 32996717
DOI: 10.1111/aos.14629 -
Journal of Ophthalmology 2022We performed a systematic review and meta-analysis to evaluate the association between cataract surgery and the development and progression of AMD. (Review)
Review
PURPOSE
We performed a systematic review and meta-analysis to evaluate the association between cataract surgery and the development and progression of AMD.
METHODS
This meta-analysis was registered at PROSPERO (CRD42017077962). We conducted a systematic literature search in August 2020 in Embase and PubMed and included cohort studies, case-control studies, or randomized controlled trials (RCTs) if they examined the association between cataract surgery and AMD. Odds ratio (OR) was used as a measure of the association with a random effect model. The analysis was further stratified by factors that could affect the outcomes.
RESULTS
15 studies were included in this study. In the overall analysis, cataract surgery was significantly associated with the incidence of late AMD (OR, 1.80; 95% CI, 1.26-2.56; = 0.001), particularly geographic atrophy (OR, 3.20; 95% CI, 1.90-5.39; ≤ 0.001). No significant associations were observed between cataract surgery and the incidence of early AMD. Subgroup analysis showed that the OR for incidence of early and late AMD was significantly higher for cataract surgery performed more than 5 years compared with less than 5 years. We also found an increased risk of progression of AMD after cataract surgery performed more than 5 years (OR, 1.97; 95% CI, 1.29-3.01; = 0.002).
CONCLUSIONS
Our results suggest that cataract surgery may be associated with an increased risk of late AMD development and AMD progression. In addition, increasing the follow-up time since cataract surgery may further increase the risk for the development and progression of AMD. In the future, prospective multicenter studies with well-designed RCTs are required to confirm our findings.
PubMed: 35573811
DOI: 10.1155/2022/6780901