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Indian Journal of Ophthalmology Nov 2023Intravitreal injection of anti- Vascular Endothelial Growth Factor (VEGF)is commonly used to treat patients with diabetic macular edema (DME). However, the injection...
Intravitreal injection of anti- Vascular Endothelial Growth Factor (VEGF)is commonly used to treat patients with diabetic macular edema (DME). However, the injection alone requires high cost and compliance. Combining micropulse subthreshold laser (MPSL) and anti-VEGF is a new approach to treating DME. This study intended to answer the question of whether MPSL plus anti-VEGF is effective compared to anti-VEGF alone. The following terms were used in PubMed, clinicaltrial.gov, and Google Scholar: anti-VEGF, DME, MPSL, and diabetic retinopathy. All studies of DME comparing the intervention of MPSL plus anti-VEGF and VEGF alone between the years 2017-2021 were included. Studies with no comparison between the intervention and control group, abstract-only papers, case reports, case series, and systematic review studies were excluded. Five Randomized Controlled Trial (RCTs) and three retrospective studies were analyzed. Four studies found that best-corrected visual acuity (BCVA) improved in both therapies. Central macular thickness in six studies was also improved. The improvement differences between both therapies were insignificant and the number of anti-VEGF injections was significantly lower in combination therapy. These studies show equal outcomes of both therapies. The reduced number of anti-VEGF injections of the combination therapy could improve the management of DME in terms of cost-effectiveness. Further analysis should be conducted to pool the data from the studies and evaluate the overall outcome.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetes Mellitus; Diabetic Retinopathy; Intravitreal Injections; Lasers; Macular Edema; Ranibizumab; Retrospective Studies; Vascular Endothelial Growth Factor A
PubMed: 37870005
DOI: 10.4103/IJO.IJO_519_23 -
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 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Genes Jul 2023(1) Background: encodes a nuclear receptor transcription factor that is considered to promote cell differentiation, affect retinal development, and regulate...
(1) Background: encodes a nuclear receptor transcription factor that is considered to promote cell differentiation, affect retinal development, and regulate phototransduction in rods and cones. This study aimed to analyze the clinical characteristics and observe the prognosis of autosomal dominant retinopathy (ADRP) and autosomal recessive retinopathy (ARRP) associated with ; (2) Methods: variants were collected from our exome sequencing data and identified per the American College of Medical Genetics and Genomics criteria. Data from our cohort and a systemic literature review were conducted to explore the variants spectrum and potential genotype-phenotype correlations; (3) Results: Nine pathogenic variants/likely pathogenic variants in , including five novel variants, were detected in eight families (four each with ADRP and ARRP). Follow-up data showed schisis/atrophy in the macula and retinal degeneration initiation around the vascular arcades with differences in ADRP and ARRP. A systemic literature review indicated patients with ADRP presented better visual acuity ( < 0.01) and later onset age ( < 0.0001) than did those with ARRP; (4) Conclusions: Macular schisis and retinal degeneration around vascular arcades may present as the prognosis of -retinopathy, dominant, or recessive. Our data might further enrich our understanding of variants and associated inherited retinopathy.
Topics: Humans; Atrophy; Longitudinal Studies; Orphan Nuclear Receptors; Retinal Degeneration
PubMed: 37628579
DOI: 10.3390/genes14081525 -
Journal of Ophthalmic & Vision Research 2023This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed,... (Review)
Review
This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.
PubMed: 37600916
DOI: 10.18502/jovr.v18i3.13780 -
BMJ Open Aug 2023To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to reduce MVCs.
DESIGN
Medline (Ovid), EMBASE and Global Health electronic databases were systematically searched from inception to March 2022 for observational and interventional English-language studies. Screening, data extraction and appraisals using the Joanna Briggs Institute appraisal tools were completed by two reviewers independently. Where appropriate, measures of association were converted into risk ratios (RRs) or ORs for meta-analysis.
PARTICIPANTS
Drivers of four-wheeled vehicles of all ages with no cognitive declines.
PRIMARY AND SECONDARY OUTCOMES
MVC involvement (primary) and driving cessation (secondary).
RESULTS
101 studies (n=778 052) were included after full-text review. 57 studies only involved older drivers (≥65 years) and 85 were in high-income settings. Heterogeneity in the data meant that most meta-analyses were underpowered as only 25 studies, further split into different groups of eye diseases and measures of vision, could be meta-analysed. The limited evidence from the meta-analyses suggests that visual field defects (four studies; RR 1.51 (95% CI 1.23, 1.85); p<0.001; I=46.79%), and contrast sensitivity (two studies; RR 1.40 (95% CI 1.08, 1.80); p=0.01, I=0.11%) and visual acuity loss (five studies; RR 1.21 (95% CI 1.02, 1.43); p=0.03, I=28.49%) may increase crash risk. The results are more inconclusive for available evidence for associations of glaucoma (five studies, RR 1.27 (95% CI 0.67, 2.42); p=0.47; I=93.48%) and cataract (two studies RR 1.15 (95% CI 0.97, 1.36); p=0.11; I=3.96%) with crashes. Driving cessation may also be linked with glaucoma (two studies; RR 1.62 (95% CI 1.20, 2.19); p<0.001, I=22.45%), age-related macular degeneration (AMD) (three studies; RR 2.21 (95% CI 1.47, 3.31); p<0.001, I=75.11%) and reduced contrast sensitivity (three studies; RR 1.30 (95% CI 1.05, 1.61); p=0.02; I=63.19%). Cataract surgery halved MVC risk (three studies; RR 0.55 (95% CI 0.34, 0.92); p=0.02; I=97.10). Ranibizumab injections (four randomised controlled trials) prolonged driving in persons with AMD.
CONCLUSION
Impaired vision identified through a variety of measures is associated with both increased MVC involvement and cessation. Cataract surgery can reduce MVC risk. Despite literature being highly heterogeneous, this review shows that detection of vision problems and appropriate treatment are critical to road safety.
PROSPERO REGISTRATION NUMBER
CRD42020172153.
Topics: Humans; Visual Acuity; Ranibizumab; Accidents, Traffic; Macular Degeneration; Vision Disorders; Cataract
PubMed: 37567751
DOI: 10.1136/bmjopen-2022-065210 -
Journal of Clinical Medicine Jul 2023Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We... (Review)
Review
Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms:
AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI. PubMed: 37510788
DOI: 10.3390/jcm12144671 -
Diagnostics (Basel, Switzerland) Jul 2023The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine.... (Review)
Review
The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine. Ophthalmology sits at the forefront of this transformation thanks to the effortless acquisition of an abundance of imaging modalities. There has been tremendous work in the field of AI for retinal diseases, with age-related macular degeneration being at the top of the most studied conditions. The purpose of the current systematic review was to identify and evaluate, in terms of strengths and limitations, the articles that apply AI to optical coherence tomography (OCT) images in order to predict the future evolution of age-related macular degeneration (AMD) during its natural history and after treatment in terms of OCT morphological structure and visual function. After a thorough search through seven databases up to 1 January 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1800 records were identified. After screening, 48 articles were selected for full-text retrieval and 19 articles were finally included. From these 19 articles, 4 articles concentrated on predicting the anti-VEGF requirement in neovascular AMD (nAMD), 4 articles focused on predicting anti-VEGF efficacy in nAMD patients, 3 articles predicted the conversion from early or intermediate AMD (iAMD) to nAMD, 1 article predicted the conversion from iAMD to geographic atrophy (GA), 1 article predicted the conversion from iAMD to both nAMD and GA, 3 articles predicted the future growth of GA and 3 articles predicted the future outcome for visual acuity (VA) after anti-VEGF treatment in nAMD patients. Since using AI methods to predict future changes in AMD is only in its initial phase, a systematic review provides the opportunity of setting the context of previous work in this area and can present a starting point for future research.
PubMed: 37510207
DOI: 10.3390/diagnostics13142464 -
BMJ Open Ophthalmology Jun 2023This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular... (Meta-Analysis)
Meta-Analysis
TOPIC
This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD).
METHODS
We conducted systematic searches from January 2003 to August 2022 on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials. We included studies reporting changes in early treatment diabetic retinopathy study-measured best-corrected visual acuity (BCVA), number of patients who lost or gained more than 15 letters in BCVA from baseline, changes in retinal thickness and adverse events between treatment arms. The following studies were excluded: studies that did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF agents with laser or steroid injections, sham injections as a control comparator, studies without English full texts and non-comparative, observational study design.
RESULTS
Five studies reported on four randomised controlled trials (RCTs) and 1544 eyes at baseline were included in this systematic review and meta-analysis. The studies in our systematic review found no significant differences between reference ranibizumab and ranibizumab biosimilar medications (FYB201, SB11, RanizuRel and Lupin's ranibizumab) for visual and anatomical outcomes. No significant differences were detected between biosimilar and reference ranibizumab for treatment emergent adverse events (risk ratio, RR 1.06, 95% CI (0.91 to 1.23), p=0.45, I=52%) or IOP-related adverse events with significant heterogeneity (RR 2.59, 95% CI (0.11 to 62.25), p=0.56, I=76%).
CONCLUSION
This systematic review of four RCTs demonstrated no significant difference in visual outcomes, retinal thickness outcomes, as well as meta-analysis of adverse events between biosimilar and reference ranibizumab therapies for nAMD treatment.
Topics: Humans; Ranibizumab; Biosimilar Pharmaceuticals; Angiogenesis Inhibitors; Bevacizumab; Vascular Endothelial Growth Factor A; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factors; Observational Studies as Topic
PubMed: 37493655
DOI: 10.1136/bmjophth-2022-001205 -
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