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Acta Ophthalmologica May 2018There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized... (Meta-Analysis)
Meta-Analysis Review
There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 μmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 μmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn.
Topics: Biomarkers; Global Health; Homocysteine; Humans; Hyperhomocysteinemia; Incidence; Risk Factors; Wet Macular Degeneration
PubMed: 27966830
DOI: 10.1111/aos.13343 -
The British Journal of Ophthalmology Dec 2020To investigate the prevalence of myopic macular degeneration (MMD) in the global population. (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the prevalence of myopic macular degeneration (MMD) in the global population.
METHODS
All published literature of population-based studies on MMD prevalence worldwide were searched and only those with clear definitions to diagnose and classify MMD lesions by standardised grading methods were selected. Meta-analysis methods were used to calculate the pooled prevalence of MMD and its 95% CI in a random-effects model. The prevalence of MMD lesions would also be reported, together with the subgroup analysis of age, region and gender. Correlation between MMD prevalence and spherical equivalent levels and axial length were also evaluated.
RESULTS
12 studies with 58 558 subjects were included in this meta-analysis. The pooled prevalence of MMD in the world population was 2.1% (95% CI: 1.3% to 3.3%). In the subgroup analysis, people with the following characteristics were at higher risk of developing MMD: female, urban life, living in Asia, older age, longer axial length and severer myopia.
CONCLUSIONS
MMD is a serious public health concern worldwide, particularly in subjects who are women, subjects living in urban areas, subjects living in Asia, and subjects with longer axial lengths and severer myopia. Further studies from other continents/ethnicities are needed for comprehensive estimates of the prevalence of MMD globally.
Topics: Global Health; Humans; Macular Degeneration; Myopia, Degenerative; Prevalence; Refraction, Ocular; Visual Acuity
PubMed: 32188679
DOI: 10.1136/bjophthalmol-2019-315298 -
Maturitas Jun 2016Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of... (Meta-Analysis)
Meta-Analysis Review
Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD.
Topics: Cross-Sectional Studies; Humans; Macular Degeneration; Vitamin D; Vitamin D Deficiency
PubMed: 27105707
DOI: 10.1016/j.maturitas.2016.04.002 -
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 -
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 -
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 -
Ophthalmic Epidemiology Apr 2022Age-related macular degeneration (AMD), a leading cause of irreversible blindness, increases fall risk through impaired central vision. Falls place an enormous economic...
PURPOSE
Age-related macular degeneration (AMD), a leading cause of irreversible blindness, increases fall risk through impaired central vision. Falls place an enormous economic burden on healthcare systems. We hypothesized that AMD treatments may reduce patients' falls risk. This systematic review (ID #: 172623) synthesized the current understanding of wet and dry AMD treatments' impact on patient falls and mobility, connecting these two public health issues.
METHODS
On April 17, 2020, PubMed, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials were queried. Clinical trials and observational studies were included, while non-English and non-primary studies were excluded. Two authors screened, extracted data, and assessed bias using RoB-2 and ROBINS-I. A third author served as a tie breaker.
RESULTS
This database search resulted in 3,525 studies, with an additional 112 identified through bibliography review. Ten articles met eligibility criteria. Most studies featured the outcome of interest as a secondary outcome (n = 4) and patient-reported adverse events (n = 5), rather than a primary focus (n = 2). Ten out of the 11 outcomes had a moderate to serious risk of bias. No two studies used the same instrument to measure falls or mobility.
CONCLUSION
Despite the potential positive impact of AMD treatments on patient falls and mobility, quality data on this relationship are lacking. This work underscores the need to broaden ophthalmologic research outcomes beyond visual parameters to include patient-centred, functional measures. Incorporating standardized methods to track falls and screen for difficulty with walking and balance would enable evaluation of AMD treatments on functional outcomes, potentially helping guide management.
Topics: Accidental Falls; Geographic Atrophy; Humans; Macular Degeneration; Visual Acuity
PubMed: 33993827
DOI: 10.1080/09286586.2021.1921227 -
The Cochrane Database of Systematic... Jun 2023Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as... (Review)
Review
BACKGROUND
Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as populations age, AMD remains incurable and there are no treatments for most patients. Mounting genetic and molecular evidence implicates complement system overactivity as a key driver of AMD development and progression. The last decade has seen the development of several novel therapeutics targeting complement in the eye for the treatment of AMD. This review update encompasses the results of the first randomised controlled trials in this field.
OBJECTIVES
To assess the effects and safety of complement inhibitors in the prevention or treatment of AMD.
SEARCH METHODS
We searched CENTRAL on the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP to 29 June 2022 with no language restrictions. We also contacted companies running clinical trials for unpublished data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with parallel groups and comparator arms that studied complement inhibition for advanced AMD prevention/treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed search results and resolved discrepancies through discussion. Outcome measures evaluated at one year included change in best-corrected visual acuity (BCVA), untransformed and square root-transformed geographic atrophy (GA) lesion size progression, development of macular neovascularisation (MNV) or exudative AMD, development of endophthalmitis, loss of ≥ 15 letters of BCVA, change in low luminance visual acuity, and change in quality of life. We assessed risk of bias and evidence certainty using Cochrane risk of bias and GRADE tools.
MAIN RESULTS
Ten RCTs with 4052 participants and eyes with GA were included. Nine evaluated intravitreal (IVT) administrations against sham, and one investigated an intravenous agent against placebo. Seven studies excluded patients with prior MNV in the non-study eye, whereas the three pegcetacoplan studies did not. The risk of bias in the included studies was low overall. We also synthesised results of two intravitreal agents (lampalizumab, pegcetacoplan) at monthly and every-other-month (EOM) dosing intervals. Efficacy and safety of IVT lampalizumab versus sham for GA For 1932 participants in three studies, lampalizumab did not meaningfully change BCVA given monthly (+1.03 letters, 95% confidence interval (CI) -0.19 to 2.25) or EOM (+0.22 letters, 95% CI -1.00 to 1.44) (high-certainty evidence). For 1920 participants, lampalizumab did not meaningfully change GA lesion growth given monthly (+0.07 mm², 95% CI -0.09 to 0.23; moderate-certainty due to imprecision) or EOM (+0.07 mm², 95% CI -0.05 to 0.19; high-certainty). For 2000 participants, lampalizumab may have also increased MNV risk given monthly (RR 1.77, 95% CI 0.73 to 4.30) and EOM (RR 1.70, 95% CI 0.67 to 4.28), based on low-certainty evidence. The incidence of endophthalmitis in patients treated with monthly and EOM lampalizumab was 4 per 1000 (0 to 87) and 3 per 1000 (0 to 62), respectively, based on moderate-certainty evidence. Efficacy and safety of IVT pegcetacoplan versus sham for GA For 242 participants in one study, pegcetacoplan probably did not meaningfully change BCVA given monthly (+1.05 letters, 95% CI -2.71 to 4.81) or EOM (-1.42 letters, 95% CI -5.25 to 2.41), as supported by moderate-certainty evidence. In contrast, for 1208 participants across three studies, pegcetacoplan meaningfully reduced GA lesion growth when given monthly (-0.38 mm², 95% CI -0.57 to -0.19) and EOM (-0.29 mm², 95% CI -0.44 to -0.13), with high certainty. These reductions correspond to 19.2% and 14.8% versus sham, respectively. A post hoc analysis showed possibly greater benefits in 446 participants with extrafoveal GA given monthly (-0.67 mm², 95% CI -0.98 to -0.36) and EOM (-0.60 mm², 95% CI -0.91 to -0.30), representing 26.1% and 23.3% reductions, respectively. However, we did not have data on subfoveal GA growth to undertake a formal subgroup analysis. In 1502 participants, there is low-certainty evidence that pegcetacoplan may have increased MNV risk when given monthly (RR 4.47, 95% CI 0.41 to 48.98) or EOM (RR 2.29, 95% CI 0.46 to 11.35). The incidence of endophthalmitis in patients treated with monthly and EOM pegcetacoplan was 6 per 1000 (1 to 53) and 8 per 1000 (1 to 70) respectively, based on moderate-certainty evidence. Efficacy and safety of IVT avacincaptad pegol versus sham for GA In a study of 260 participants with extrafoveal or juxtafoveal GA, monthly avacincaptad pegol probably did not result in a clinically meaningful change in BCVA at 2 mg (+1.39 letters, 95% CI -5.89 to 8.67) or 4 mg (-0.28 letters, 95% CI -8.74 to 8.18), based on moderate-certainty evidence. Despite this, the drug was still found to have probably reduced GA lesion growth, with estimates of 30.5% reduction at 2 mg (-0.70 mm², 95% CI -1.99 to 0.59) and 25.6% reduction at 4 mg (-0.71 mm², 95% CI -1.92 to 0.51), based on moderate-certainty evidence. Avacincaptad pegol may have also increased the risk of developing MNV (RR 3.13, 95% CI 0.93 to 10.55), although this evidence is of low certainty. There were no cases of endophthalmitis reported in this study.
AUTHORS' CONCLUSIONS
Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.
Topics: Humans; Administration, Intravenous; Complement Inactivating Agents; Endophthalmitis; Geographic Atrophy; Macular Degeneration
PubMed: 37314061
DOI: 10.1002/14651858.CD009300.pub3 -
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 -
Ophthalmology Science 2024Though lipid and cholesterol dyshomeostasis is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), there is no consensus regarding which... (Review)
Review
TOPIC
Though lipid and cholesterol dyshomeostasis is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), there is no consensus regarding which elements of systemic lipid homeostasis are perturbed in AMD. In this systematic review and meta-analysis, an update to that performed by Wang et al in 2016, we characterized serum lipoprotein profiles in patients with AMD and its various stages.
CLINICAL RELEVANCE
These findings may identify novel therapeutic approaches for AMD, a leading cause of blindness among older adults in the industrialized world.
METHODS
We used MEDLINE, Embase, and Web of Science to identify articles from database inception to May 2022 that reported blood/serum levels of lipid subspecies (triglycerides [TGs], total cholesterol [TC], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) in patients with AMD compared with controls. We meta-analyzed the data by generating multilevel random-effects models using restricted maximum likelihood estimation.
RESULTS
Our updated meta-analysis included 56 studies, almost 3 times as many studies as the 2016 meta-analysis with a total of 308 188 participants. There were no significant differences in serum TG, TC, LDL, or HDL between patients with AMD and non-AMD controls. Given significant heterogeneity, we performed subanalyses specifically in patients with early to intermediate nonexudative AMD, advanced nonexudative AMD, and advanced exudative AMD. Compared with non-AMD controls, patients with early to intermediate nonexudative AMD had significantly lower serum TG (standardized mean difference [SMD]: -0.03; 95% confidence interval [95% CI]: -0.06 to -0.01) and higher serum HDL (SMD: 0.07; 95% CI: 0.04-0.11). Patients with advanced exudative AMD had significantly higher serum LDL (SMD: 0.33; 95% CI: 0.04-0.62) compared with non-AMD controls. There were no other significant differences identified.
CONCLUSION
We found that there is significant heterogeneity in systemic lipoproteins in patients with AMD compared with non-AMD controls. The specific pattern of lipid dyshomeostasis appeared to be distinct based on AMD stage. These findings highlight both the underlying heterogeneity of AMD as well as the presence of distinct pathophysiological mechanisms involved at different stages or subtypes of AMD and may inform the development of novel therapeutic approaches.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 37869027
DOI: 10.1016/j.xops.2023.100341