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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 -
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 -
Frontiers in Neuroscience 2021Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation...
Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation strategies. One way to do this is through visual impairment simulations. The aim of this review is to synthesize and assess the types of simulation methods that have been used to simulate age-related macular degeneration (AMD) in normally sighted participants, during activities of daily living (e.g., reading, cleaning, and cooking). We conducted a systematic literature search in five databases and a critical analysis of the advantages and disadvantages of various AMD simulation methods (following PRISMA guidelines). The review focuses on the suitability of each method for investigating activities of daily living, an assessment of clinical validation procedures, and an evaluation of the adaptation periods for participants. Nineteen studies met the criteria for inclusion. Contact lenses, computer manipulations, gaze contingent displays, and simulation glasses were the main forms of AMD simulation identified. The use of validation and adaptation procedures were reported in approximately two-thirds and half of studies, respectively. Synthesis of the methodology demonstrated that the choice of simulation has been, and should continue to be, guided by the nature of the study. While simulations may never completely replicate vision loss experienced during AMD, consistency in simulation methodology is critical for generating realistic behavioral responses under vision impairment simulation and limiting the influence of confounding factors. Researchers could also come to a consensus regarding the length and form of adaptation by exploring what is an adequate amount of time and type of training required to acclimatize participants to vision impairment simulations.
PubMed: 34483815
DOI: 10.3389/fnins.2021.663062 -
Frontiers in Medicine 2023Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective...
Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective of this review is to assess the most recent research on the ideal dietary approach to prevent or support the treatment of DR, AMD, and cataracts, as well as to construct a food pyramid that makes it simple for people who are at risk of developing these pathologies to decide what to eat. The food pyramid presented here proposes what should be consumed every day: 3 portions of low glycemic index (GI) grains (for fiber and zinc content), 5 portions (each portion: ≥200 g/day) of fruits and vegetables (spinach, broccoli, zucchini cooked, green leafy vegetables, orange, kiwi, grapefruit for folic acid, vitamin C, and lutein/zeaxanthin content, at least ≥42 μg/day, are to be preferred), extra virgin olive (EVO) oil (almost 20 mg/day for vitamin E and polyphenols content), nuts or oil seeds (20-30 g/day, for zinc content, at least ≥15.8 mg/day); weekly: fish (4 portions, for omega-3 content and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) 0.35-1.4 g/day), white meat (3 portions for vitamin B12 content), legumes (2 portions for vegetal proteins), eggs (2 portions for lutein/zeaxanthin content), light cheeses (2 portions for vitamin B6 content), and almost 3-4 times/week microgreen and spices (saffron and curcumin). At the top of the pyramid, there are two pennants: one green, which indicates the need for personalized supplementation (if daily requirements cannot be met through diet, omega-3, and L-methylfolate supplementation), and one red, which indicates that certain foods are prohibited (salt and sugar). Finally, 3-4 times per week, 30-40 min of aerobic and resistance exercises are required.
PubMed: 37324128
DOI: 10.3389/fmed.2023.1168560 -
Antioxidants (Basel, Switzerland) Aug 2021Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses... (Review)
Review
Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue. The aim of this systematic review is to examine the neuroprotective potential of the xanthophyll carotenoids lutein, zeaxanthin, and -zeaxanthin on retinal neurodegeneration for the purpose of adjunctive nutraceutical strategy in the management of AMD. A comprehensive literature review was performed to retrieve 55 eligible publications, using four database searches from PubMed, Embase, Cochrane Library, and the Web of Science. Epidemiology studies indicated an enhanced risk reduction against late AMD with greater dietary consumption of carotenoids, meanwhile greater concentrations in macular pigment demonstrated significant improvements in visual function among AMD patients. Collectively, evidence strongly suggests that carotenoid vitamin therapies offer remarkable synergic protection in the neurosensory retina, with the potential to serve as adjunctive nutraceutical therapy in the management of established AMD, albeit these benefits may vary among different stages of disease.
PubMed: 34439503
DOI: 10.3390/antiox10081255 -
Methods in Enzymology 2022The term "macular carotenoids" refers to the lutein, zeaxanthin, and meso-zeaxanthin that are highly concentrated at the center of the human retina. Intraretinal levels...
The term "macular carotenoids" refers to the lutein, zeaxanthin, and meso-zeaxanthin that are highly concentrated at the center of the human retina. Intraretinal levels of these carotenoids are inversely associated with the risk of age-related macular degeneration (AMD), and oral supplementation with these carotenoids can significantly reduce AMD risk. To make macular carotenoid analysis more accessible, we systematically review the current methods for extraction, detection, and imaging of macular carotenoids in both basic and clinical research. We first introduce carotenoid extraction methods from the retina, retinal pigment epithelium (RPE)/choroid, serum, and liver of the human and animal models, such as mice and Japanese quails, as well as from algae, bacteria, and chicken egg yolks and cultured cells. We then review macular carotenoid detection by spectroscopy and HPLC, while particularly introducing carotenoid separation via cyano columns, chiral columns, and C30 columns. In the end, we summarize the common methods used to image carotenoids in living human eyes: resonance Raman spectroscopy, autofluorescence attenuation spectroscopy, and reflection spectroscopy, and we then review the utility of confocal resonance Raman microscopy to image the macular carotenoids in tissue sections of human and mouse retinas.
Topics: Animals; Carotenoids; Chromatography, High Pressure Liquid; Humans; Lutein; Mice; Retina; Spectrum Analysis, Raman
PubMed: 36008007
DOI: 10.1016/bs.mie.2022.05.001 -
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