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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 -
Frontiers in Neurology 2024Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome...
BACKGROUND
Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes.
METHODS
The plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins.
RESULTS
SMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures.
CONCLUSION
Proteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation.
PubMed: 38903171
DOI: 10.3389/fneur.2024.1400557 -
Journal of Proteome Research Jun 2024Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related...
Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting . Moreover, studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.
PubMed: 38902972
DOI: 10.1021/acs.jproteome.4c00195 -
Archives of Pharmacal Research Jun 2024Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD,... (Review)
Review
Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD, also known as exudative or neovascular AMD, is less common but more severe than dry AMD and is responsible for 90% of the visual impairment caused by AMD and affects 20 million people worldwide. Current treatment options mainly involve biologics that inhibit the vascular endothelial growth factor or complement pathways. However, these treatments have limitations such as high cost, injection-related risks, and limited efficacy. Therefore, new therapeutic targets and strategies have been explored to improve the outcomes of patients with AMD. A promising approach is the use of small-molecule drugs that modulate different factors involved in AMD pathogenesis, such as tyrosine kinases and integrins. Small-molecule drugs offer advantages, such as oral administration, low cost, good penetration, and increased specificity for the treatment of wet and dry AMD. This review summarizes the current status and prospects of small-molecule drugs for the treatment of wet AMD. These advances are expected to support the development of effective and targeted treatments for patients with AMD.
Topics: Humans; Macular Degeneration; Small Molecule Libraries; Animals; Angiogenesis Inhibitors; Wet Macular Degeneration; Drug Development; Vascular Endothelial Growth Factor A
PubMed: 38902481
DOI: 10.1007/s12272-024-01503-3 -
Canadian Journal of Ophthalmology.... Jun 2024To compare the visibility and accessibility of the outer retina in neovascular age-related macular degeneration (nAMD) between 2 OCT devices.
OBJECTIVE
To compare the visibility and accessibility of the outer retina in neovascular age-related macular degeneration (nAMD) between 2 OCT devices.
METHODS
In this prospective, cross-sectional exploratory study, differences in thickness and loss of individual outer retinal layers in eyes with nAMD and in age-matched healthy eyes between a next-level High-Res OCT device and the conventional SPECTRALIS OCT (both Heidelberg Engineering GmbH, Heidelberg, Germany) were analyzed. Eyes with nAMD and at least 250 nL of retinal fluid, quantified by an approved deep-learning algorithm (Fluid Monitor, RetInSight, Vienna, Austria), fulfilled the inclusion criteria. The outer retinal layers were segmented using automated layer segmentation and were corrected manually. Layer loss and thickness were compared between both devices using a linear mixed-effects model and a paired t test.
RESULTS
Nineteen eyes of 17 patients with active nAMD and 17 healthy eyes were included. For nAMD eyes, the thickness of the retinal pigment epithelium (RPE) differed significantly between the devices (25.42 μm [95% CI, 14.24-36.61] and 27.31 μm [95% CI, 16.12-38.50] for high-resolution OCT and conventional OCT, respectively; p = 0.033). Furthermore, a significant difference was found in the mean relative external limiting membrane loss (p = 0.021). However, the thickness of photoreceptors, RPE integrity loss, and photoreceptor integrity loss did not differ significantly between devices in the central 3 mm. In healthy eyes, a significant difference in both RPE and photoreceptor thickness between devices was shown (p < 0.001).
CONCLUSION
Central RPE thickness was significantly thinner on high-resolution OCT compared with conventional OCT images explained by superior optical separation of the RPE and Bruch's membrane.
PubMed: 38901467
DOI: 10.1016/j.jcjo.2024.05.014 -
JAMA Ophthalmology Jun 2024Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more...
IMPORTANCE
Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications.
OBJECTIVE
To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022.
INTERVENTIONS
Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks.
MAIN OUTCOMES AND MEASURES
IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection.
RESULTS
Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm.
CONCLUSIONS AND RELEVANCE
Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.
PubMed: 38900484
DOI: 10.1001/jamaophthalmol.2024.2061 -
Investigative Ophthalmology & Visual... Jun 2024The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in...
PURPOSE
The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD).
METHODS
The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions.
RESULTS
Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy.
CONCLUSIONS
HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.
Topics: Humans; Tomography, Optical Coherence; Male; Female; Cross-Sectional Studies; Aged; Wet Macular Degeneration; Fluorescein Angiography; Aged, 80 and over; Recurrence; Visual Acuity; Angiogenesis Inhibitors; Fundus Oculi; Retrospective Studies; Middle Aged; Exudates and Transudates
PubMed: 38899961
DOI: 10.1167/iovs.65.6.30 -
Scientific Reports Jun 2024Neovascular age-related macular degeneration (nAMD) is a prevalent cause of permanent vision loss and blindness in the elderly worldwide, with a significant impact on...
Neovascular age-related macular degeneration (nAMD) is a prevalent cause of permanent vision loss and blindness in the elderly worldwide, with a significant impact on patients' daily lives. However, burdens related to nAMD from the patients' perspective have not been well documented. Here we developed a new questionnaire after eliciting nAMD patients' daily challenges followed by a pilot survey. Seven daily life burden domains were identified, and a quantitative survey was conducted using the questionnaire in the real-world clinic. Of the total 153 participants (mean age, 76.3 ± 8.3 years), 67 (43.8%) had bilateral nAMD, and 79 (52.7%) were classified into severe nAMD according to the best-corrected visual acuity with cut-off value of 0.52 in logMAR. Patients with bilateral and severe nAMD had significantly higher burden scores across all domains. Network models for the bilateral and severe disease subgroups identified the interactions between "activity of daily living" and "hand-eye coordination" and between "use of electronic devices" and "face recognition" domains, which were considered to be important burdens for the patients. These results can advance ophthalmologists' understanding of the impact of nAMD on patients' daily lives and the importance of active and continuing treatment for patients with nAMD.
Topics: Humans; Female; Male; Aged; Activities of Daily Living; Aged, 80 and over; Surveys and Questionnaires; Macular Degeneration; Visual Acuity; Quality of Life; Cost of Illness
PubMed: 38898138
DOI: 10.1038/s41598-024-65089-y