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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 -
Nature Communications Jun 2024Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of...
Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.
Topics: Humans; Retinal Degeneration; Male; Female; Tomography, Optical Coherence; Adult; Middle Aged; Disease Progression; Multiple Sclerosis, Relapsing-Remitting; Retina; Multiple Sclerosis, Chronic Progressive; Magnetic Resonance Imaging; Prognosis; Nerve Fibers; Retinal Ganglion Cells
PubMed: 38897994
DOI: 10.1038/s41467-024-49309-7 -
International Journal of Ophthalmology 2024With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential... (Review)
Review
With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.
PubMed: 38895690
DOI: 10.18240/ijo.2024.06.20 -
International Journal of Ophthalmology 2024To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular...
AIM
To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line.
METHODS
Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of and , , , genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR).
RESULTS
The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of , , , , and after treatment with both free and niosomal AUR.
CONCLUSION
Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.
PubMed: 38895680
DOI: 10.18240/ijo.2024.06.06 -
Journal of Clinical Medicine May 2024: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal...
: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal diseases. : High-resolution OCT scans from the publicly available Kaggle dataset and a local dataset were used by four state-of-the-art self-supervised frameworks. The backbone model of all the frameworks was a pre-trained convolutional neural network (CNN), which enabled the extraction of meaningful features from OCT images. Anomalous images included choroidal neovascularization (CNV), diabetic macular edema (DME), and the presence of drusen. Anomaly detectors were evaluated by commonly accepted performance metrics, including area under the receiver operating characteristic curve, F1 score, and accuracy. : A total of 25,315 high-resolution retinal OCT slabs were used for training. Test and validation sets consisted of 968 and 4000 slabs, respectively. The best performing across all anomaly detectors had an area under the receiver operating characteristic of 0.99. All frameworks were shown to achieve high performance and generalize well for the different retinal diseases. Heat maps were generated to visualize the quality of the frameworks' ability to localize anomalous areas of the image. : This study shows that with the use of pre-trained feature extractors, the frameworks tested can generalize to the domain of retinal OCT scans and achieve high image-level ROC-AUC scores. The localization results of these frameworks are promising and successfully capture areas that indicate the presence of retinal pathology. Moreover, such frameworks have the potential to uncover new biomarkers that are difficult for the human eye to detect. Frameworks for anomaly detection and localization can potentially be integrated into clinical decision support and automatic screening systems that will aid ophthalmologists in patient diagnosis, follow-up, and treatment design. This work establishes a solid basis for further development of automated anomaly detection frameworks for clinical use.
PubMed: 38892804
DOI: 10.3390/jcm13113093