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PeerJ 2024To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis.
MATERIALS AND METHODS
Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed.
RESULTS
Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], > 0.05].
CONCLUSIONS
Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.
Topics: Humans; Angiogenesis Inhibitors; Macular Degeneration; Antibodies, Monoclonal, Humanized; Visual Acuity; Treatment Outcome; Intravitreal Injections; Wet Macular Degeneration
PubMed: 38915383
DOI: 10.7717/peerj.17561 -
Translational Vision Science &... Jun 2024To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
PURPOSE
To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
METHODS
This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis.
RESULTS
In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group.
CONCLUSIONS
AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors.
TRANSLATIONAL RELEVANCE
Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data.
Topics: Humans; Aqueous Humor; Female; Proteomics; Male; Aged; Metabolomics; Eye Proteins; Middle Aged; Cataract; Diabetic Retinopathy; Macular Edema; Wet Macular Degeneration; Aged, 80 and over
PubMed: 38913008
DOI: 10.1167/tvst.13.6.17 -
The Canadian Journal of Urology Jun 2024
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Anticoagulants
PubMed: 38912937
DOI: No ID Found -
The Canadian Journal of Urology Jun 2024
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Anticoagulants
PubMed: 38912936
DOI: No ID Found -
Drug Design, Development and Therapy 2024Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major... (Review)
Review
Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.
Topics: Melatonin; Humans; Diabetic Retinopathy; Macular Degeneration; Animals; Fundus Oculi; Antioxidants
PubMed: 38911030
DOI: 10.2147/DDDT.S471525 -
Ophthalmology Jun 2024To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry...
OBJECTIVE
To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD).
DESIGN
Phase 1, open-label, single-center, first-in-human clinical study.
SUBJECTS
Adult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included.
METHODS
Patients (N=17) were sequentially enrolled into low (3.56×10 viral genome [vg]/eye; n=3), intermediate (1.07×10 vg/eye; n=3), and high (3.56×10 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months.
MAIN OUTCOME MEASURES
Safety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate.
RESULTS
Baseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center-involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24.
CONCLUSIONS
All 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.
PubMed: 38909914
DOI: 10.1016/j.ophtha.2024.06.013 -
Scientific Reports Jun 2024To improve the understanding of potential pathological mechanisms of macular edema (ME), we try to discover biomarker candidates related to ME caused by diabetic...
To improve the understanding of potential pathological mechanisms of macular edema (ME), we try to discover biomarker candidates related to ME caused by diabetic retinopathy (DR) and retinal vein occlusion (RVO) in spectral-domain optical coherence tomography images by means of deep learning (DL). 32 eyes of 26 subjects with non-proliferative DR (NPDR), 77 eyes of 61 subjects with proliferative DR (PDR), 120 eyes of 116 subjects with branch RVO (BRVO), and 17 eyes of 15 subjects with central RVO (CRVO) were collected. A DL model was implemented to guide biomarker candidate discovery. The disorganization of the retinal outer layers (DROL), i.e., the gray value of the retinal tissues between the external limiting membrane (ELM) and retinal pigment epithelium (RPE), the disrupted and obscured rate of the ELM, ellipsoid zone (EZ), and RPE, was measured. In addition, the occurrence, number, volume, and projected area of hyperreflective foci (HRF) were recorded. ELM, EZ, and RPE are more likely to be obscured in RVO group and HRFs are observed more frequently in DR group (all P ≤ 0.001). In conclusion, the features of DROL and HRF can be possible biomarkers related to ME caused by DR and RVO in OCT modality.
Topics: Humans; Macular Edema; Tomography, Optical Coherence; Retinal Vein Occlusion; Diabetic Retinopathy; Female; Male; Biomarkers; Middle Aged; Aged; Retinal Pigment Epithelium; Deep Learning
PubMed: 38906954
DOI: 10.1038/s41598-024-63144-2 -
Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Tomography, Optical Coherence; Macular Degeneration; Fluorescein Angiography; Fundus Oculi; Macula Lutea; Male; Visual Acuity; Diagnosis, Differential; Female
PubMed: 38905458
DOI: 10.4103/IJO.IJO_3168_23 -
Medicine Jun 2024Diabetic Macular Edema (DME) significantly impairs vision in diabetics, with varied patient responses to current treatments like anti-vascular endothelial growth factor...
BACKGROUND
Diabetic Macular Edema (DME) significantly impairs vision in diabetics, with varied patient responses to current treatments like anti-vascular endothelial growth factor (VEGF) therapy underscoring the necessity for continued research into more effective strategies. This study aims to evaluate global research trends and identify emerging frontiers in DME to guide future research and clinical management.
METHODS
A qualitative and quantitative analysis of publications related to diabetic macular edema retrieved from the Web of Science Core Collection (WoSCC) between its inception and September 4, 2023, was conducted. Microsoft Excel, CiteSpace, VOSviewer, Bibliometrix Package, and Tableau were used for the bibliometric analysis and visualization. This encompasses an examination of the overall distribution of annual output, major countries, regions, institutions, authors, core journals, co-cited references, and keyword analyses.
RESULTS
Overall, 5624 publications were analyzed, indicating an increasing trend in DME research. The United States was identified as the leading country in DME research, with the highest h-index of 135 and 91,841 citations. Francesco Bandello emerged as the most prolific author with 97 publications. Neil M. Bressler has the highest h-index and highest total citation count of 46 and 9692, respectively. The journals "Retina - the Journal of Retinal and Vitreous Diseases" and "Ophthalmology" were highlighted as the most prominent in this field. "Retina" leads with 354 publications, a citation count of 11,872, and an h-index of 59. Meanwhile, "Ophthalmology" stands out with the highest overall citation count of 31,558 and the highest h-index of 90. The primary research focal points in diabetic macular edema included "prevalence and risk factors," "pathological mechanisms," "imaging modalities," "treatment strategies," and "clinical trials." Emerging research areas encompassed "deep learning and artificial intelligence," "novel treatment modalities," and "biomarkers."
CONCLUSION
Our bibliometric analysis delineates the leading role of the United States in DME research. We identified current research hotspots, including epidemiological studies, pathophysiological mechanisms, imaging advancements, and treatment innovations. Emerging trends, such as the integration of artificial intelligence and novel therapeutic approaches, highlight future directions. These insights underscore the importance of collaborative and interdisciplinary approaches in advancing DME research and clinical management.
Topics: Macular Edema; Bibliometrics; Humans; Diabetic Retinopathy; Biomedical Research
PubMed: 38905408
DOI: 10.1097/MD.0000000000038596 -
Bioscience Reports Jun 2024
Expression of Concern: Madecassoside protects retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis through the activation of Nrf2/HO-1 pathway.
Topics: NF-E2-Related Factor 2; Oxidative Stress; Hydrogen Peroxide; Apoptosis; Humans; Heme Oxygenase-1; Retinal Pigment Epithelium; Signal Transduction; Triterpenes; Epithelial Cells; Cell Line; Membrane Proteins; Animals
PubMed: 38904175
DOI: 10.1042/BSR-2019-4347_EOC