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Ceska a Slovenska Oftalmologie :... 2024This article presents an overview of treatment regimens of drugs containing antivascular endothelial growth factor for the treatment of neovascular form of age-related... (Review)
Review
This article presents an overview of treatment regimens of drugs containing antivascular endothelial growth factor for the treatment of neovascular form of age-related macular degeneration. Currently, drugs containing antivascular endothelial growth factor are the only effective treatment for this chronic and progressive disease. The treatment regimens for this disease in the last two decades have seen a shift from a simple endeavor to stabilize the disease to achieving maximum improvement of visual acuity and its maintenance, with improvement of the patient's quality of life and a minimal treatment burden on patients and their families. Other goals of the alternative dosing regimens that have replaced the original fixed regimens were greater individualization of the dosing regimen, better patient cooperation, saving financial costs and reducing the burden on application centers. Age-related macular degeneration, whether dry form or wet form, represents a serious health and socioeconomic problem, as the disease is one of the most common causes of severe and irreversible central visual acuity disorders up to the degree of practical blindness of one or both eyes in people over 50 years of age in developed industrialized countries. The most important issue is to ensure early diagnosis of this disease, followed by prompt and continuous treatment with an individualized proactive treatment regimen, with the aim of stabilizing and improving anatomical and functional results.
Topics: Humans; Angiogenesis Inhibitors; Macular Degeneration; Vascular Endothelial Growth Factor A; Bevacizumab
PubMed: 38925899
DOI: 10.31348/2024/25 -
Ceska a Slovenska Oftalmologie :... 2024The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to...
OBJECTIVE
The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment.
MATERIAL AND METHODS
This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated.
RESULTS
At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%).
CONCLUSION
Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).
Topics: Humans; Macular Edema; Male; Female; Diabetic Retinopathy; Dexamethasone; Retrospective Studies; Middle Aged; Aged; Intravitreal Injections; Drug Implants; Visual Acuity; Glucocorticoids; Tomography, Optical Coherence
PubMed: 38925895
DOI: 10.31348/2024/29 -
Translational Vision Science &... Jun 2024This study investigated the distribution of fundus tessellation density (FTD) in a Chinese pediatric population and its potential in reflecting early myopic maculopathy...
PURPOSE
This study investigated the distribution of fundus tessellation density (FTD) in a Chinese pediatric population and its potential in reflecting early myopic maculopathy (tessellated fundus).
METHODS
Participants were enrolled from kindergartens, primary schools, and middle schools, with cluster sampling in Shanghai, China. A series of ophthalmic examinations was conducted. Based on fundus photograph, FTD was quantitatively assessed using an artificial intelligence algorithm, and tessellated fundus was diagnosed by well-trained ophthalmologists.
RESULTS
A total of 14,234 participants aged four to 18 years were included, with 7421 boys (52.1%). Tessellated fundus was observed in 2200 (15.5%) participants. The median of FTD was 0.86% (range 0.0-42.1%). FTD increased with age and axial length. In the logistics regression, larger FTD was independently associated with tessellated fundus (P < 0.001). The area under curves of receiver operating characteristic curve for categorizing tessellated fundus using FTD was 0.774, and the cutoff point of FTD was 2.22%.
CONCLUSIONS
The density of fundus tessellation was consistent with the severity of myopia. FTD could help diagnose the early stage of myopic maculopathy, tessellated fundus, providing a new pattern for myopia screening and detection of early myopic fundus changes.
TRANSLATIONAL RELEVANCE
Quantification of fundus tessellation with artificial intelligence could help detect early myopic maculopathy.
Topics: Humans; Male; Adolescent; Child; Female; Fundus Oculi; Child, Preschool; China; ROC Curve; Myopia, Degenerative; Macular Degeneration; Artificial Intelligence; Photography
PubMed: 38922627
DOI: 10.1167/tvst.13.6.22 -
Angiogenesis Jun 2024Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV)....
BACKGROUND
Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release.
METHODS
A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3.
FINDINGS
In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3.
CONCLUSION
BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies.
PubMed: 38922557
DOI: 10.1007/s10456-024-09935-7 -
Biological Procedures Online Jun 2024Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves a variety of risk factors,...
INTRODUCTION
Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves a variety of risk factors, including lipid metabolism and inflammation. This study aims to elucidate the causal relationships between biomarkers related to these processes and AMD, leveraging Mendelian randomization (MR) and cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES).
METHOD
We conducted a two-phase study, initially using MR to explore the causality between 35 biomarkers and various AMD subtypes, followed by observational analysis with NHANES data to validate these findings.
RESULTS
MR analysis identified a protective role of TG and a risk factor role of HDL-C and CRP in AMD development. NHANES data corroborated these findings, highlighting a nuanced relationship between these biomarkers and AMD. Notably, lipid metabolism-related biomarkers showed stronger associations with early AMD, whereas CRP's significance was pronounced in late AMD.
CONCLUSION
This comprehensive analysis, combining MR with NHANES data, reinforces the importance of lipid metabolism and inflammation in AMD's etiology. Future research should further investigate these biomarkers' mechanisms and their potential as therapeutic targets for AMD prevention and treatment.
PubMed: 38918699
DOI: 10.1186/s12575-024-00248-z -
Ophthalmic Surgery, Lasers & Imaging... Jun 2024Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there... (Review)
Review
Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. .
PubMed: 38917394
DOI: 10.3928/23258160-20240430-02 -
International Ophthalmology Jun 2024To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept.
PURPOSE
To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept.
METHODS
In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab.
RESULTS
100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05).
CONCLUSIONS
Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Female; Male; Retrospective Studies; Macular Edema; Diabetic Retinopathy; Intravitreal Injections; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Tomography, Optical Coherence; Follow-Up Studies; Aged; Treatment Outcome; Drug Substitution; Vascular Endothelial Growth Factor A
PubMed: 38916818
DOI: 10.1007/s10792-024-03226-2 -
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
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; Antibodies, Monoclonal, Humanized; Intravitreal Injections; Macular Degeneration; Treatment Outcome; Visual Acuity; Wet Macular Degeneration
PubMed: 38915383
DOI: 10.7717/peerj.17561 -
Experimental Eye Research Jun 2024The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining...
The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining central/peripheral gene expression profiles may provide insight into the suitability of dogs as models for human disorders. We determined central/peripheral posterior eye gene expression profiles in dogs and interrogated inherited retinal and macular disease-associated genes for differential expression between central and peripheral regions. Bulk tissue RNA sequencing was performed on 8 mm samples of the dog central and superior peripheral regions, sampling retina and retinal pigmented epithelium/choroid separately. Reads were mapped to CanFam3.1, read counts were analyzed to determine significantly differentially expressed genes (DEGs). A similar analytic pipeline was used with a published bulk-tissue RNA sequencing human dataset. Pathways and processes involved in significantly DEGs were identified (Database for Annotation, Visualization and Integrated Discovery). Dogs and humans shared the extent and direction of central retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. Many genes implicated in heritable retinal disorders in dogs and humans were differentially expressed between central and periphery. Approximately half of genes associated with human age-related macular degeneration were differentially expressed in human and dog tissues. We have identified similarities and differences in central/peripheral gene expression profiles between dogs and humans which can be applied to further define the relevance of dogs as models for human retinal disorders.
PubMed: 38914302
DOI: 10.1016/j.exer.2024.109980 -
Experimental Eye Research Jun 2024We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular...
We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular degeneration. Human retinal pigment epithelium cells line ARPE-19 (immature) were maintained and treated with HO. The expression of CTSS, inflammatory cytokines, and complement factors induced by oxidative stress was compared between cells incubated without (control) and with CTSS knockdown (using small interfering ribonucleic acid; siRNA). To evaluate the role of CTSS in angiogenesis, we assayed tube formation using human umbilical vein endothelial cells and conditioned medium from ARPE-19 cells. We also used a mouse model of laser-induced choroidal neovascularization. CTSS levels were higher in ARPE-19 cells treated with HO than in control cells. Oxidative stress-induced CTSS resulted in significantly elevated transcription of nuclear factor kappa B-dependent inflammatory cytokines, complement factors C3a and C5a, membrane attack complex (C5b-9), and C3a and C5a receptors. siRNA-mediated knockdown of CTSS reduced the number of inflammatory signals. Furthermore, oxidative stress-induced CTSS regulated the expression of peroxisome proliferator-activated receptor γ and vascular endothelial growth factor A/ Akt serine/threonine kinase family signaling, which led to angiogenesis. Tube formation assays and mouse models of choroidal neovascularization revealed that CTSS knockdown ameliorated angiogenesis in vitro and in vivo. The present findings suggest that CTSS modulates the complement pathway, inflammatory reactions, and neovascularization, and that CTSS knockdown induces potent immunomodulatory effects. Hence, it could be a promising target for the prevention and treatment of early- and late-stage age-related macular degeneration.
PubMed: 38914301
DOI: 10.1016/j.exer.2024.109981