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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 -
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 -
Investigative Ophthalmology & Visual... Jun 2024The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying...
PURPOSE
The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms.
METHODS
In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected.
RESULTS
We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice.
CONCLUSIONS
Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.
Topics: Animals; Choroidal Neovascularization; Mice; Macrophages; rho-Associated Kinases; Mice, Knockout; Semaphorins; Disease Models, Animal; Signal Transduction; Mice, Inbred C57BL; rhoA GTP-Binding Protein; Antigens, CD; Blotting, Western; Male; Fluorescein Angiography
PubMed: 38913005
DOI: 10.1167/iovs.65.6.34 -
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