Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.

Purpose: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. Methods: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. Results: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. Conclusions: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration.

PURPOSE: To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL). RESULTS: Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (ß = 0.377, P < 0.001), avascular SHRM (ß = 0.306, P = 0.032), and ELM impairment area (ß = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (ß = 0.374, p = 0.003; ß = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (ß = 0.475, P < 0.001). CONCLUSION: The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

Analyzing Formation and Absorption of Avascular Subretinal Hyperreflective Material in nAMD From OCTA-Based Insights.

PURPOSE: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics. DESIGN: Prospective cohort study. METHODS: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption. RESULTS: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized ß = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R² of 0.453. CONCLUSIONS: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption.

A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.

BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap. METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP). RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05). CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.

The diagnostic utility of nanopore targeted sequencing in suspected endophthalmitis.

PURPOSE: This paper aimed to assess the diagnostic utility of a newly developed gene-based technology-nanopore targeted sequencing (NTS) in suspected endophthalmitis patients. METHODS: This retrospective study included 43 patients (44 eyes) with suspected endophthalmitis. NTS was applied along with microbiological culture to detect unknown pathogens in intraocular fluid samples. The diagnostic utility of NTS was mainly evaluated from three aspects, including the positivity rate of bacterial/fungal presence, diagnostic turnaround time and the frequency of change in treatment based on etiology test results. Non-parametric, two-sided Wilcoxon rank sum test, the McNemar's test and the kappa statistic were used for statistical comparisons. RESULTS: NTS showed significant advantages over traditional culture in positivity rates and diagnostic time (P < 0.001, kappa = 0.082; Z = -5.805, P < 0. 001). As regards antibiotic strategy, 17 patients (39.53%) and 5 patients (11.63%) underwent medication change following NTS and culture results respectively (P < 0.001, kappa = 0.335). With reasonable use of antibiotic and surgical intervention, most patients responded favorably, judged by significantly improved visual acuity (Z = -4.249, P < 0.001). The mean duration of hospitalization was 8.49 ± 2.45 days (range, 1-16 days). CONCLUSION: The high efficiency feature of NTS in pathogen detection renders it a valuable supplementary to traditional culture. Additionally, it has facilitated patients' management for the early and precise diagnosis of endophthalmitis.

IDENTIFICATION OF PATHOGENS IN THE INTRAOCULAR FLUID SAMPLES OF PATIENTS WITH ENDOGENOUS ENDOPHTHALMITIS USING RAPID NANOPORE TARGETED SEQUENCING.

IN BRIEF: Nanopore targeted sequencing showed a higher positivity rate and a shorter turnaround time than did traditional culture in identifying pathogens in the intraocular fluid samples of patients with endogenous endophthalmitis. PURPOSE: To evaluate the feasibility of clinical application of nanopore targeted sequencing (NTS) for the identification of pathogens in patients with endogenous endophthalmitis, especially those with fungus-associated endophthalmitis. METHODS: In this retrospective study, medical records and etiological results of 27 patients (34 eyes) with endogenous endophthalmitis were reviewed. The intraocular fluid samples were examined using both NTS and microbial culture. The results included the differences in detection time, positivity rate of pathogen detection, and positivity rate of fungus identification between two methods. RESULTS: NTS and microbial culture enabled the detection of etiologic agents in 89.28% and 35.71% of the samples, respectively. The difference of positivity rate between these methods was statistically significant ( P < 0.001). NTS also showed high sensitivity in both culture-positive and culture-negative samples (100% and 83.33%, respectively). Regarding culture-positive samples, the NTS results displayed a strong match with culture results. NTS showed a significantly higher positivity rate for fungal infection than did microbial culture (46.43% vs. 7.14%, P = 0.002). The average detection time of NTS was 1.11 ± 0.31 days, which was shorter than that of microbial culture (2.50 ± 0.58 days, Z = -4.686, P < 0.001). NTS technology facilitated an informed switch of intravitreal antimicrobial agents in 13 eyes. CONCLUSION: NTS, as a sensitive, specific, and timely complementary method, can be used along with traditional methods for the identification of pathogenic microorganisms in the intraocular fluid of patients with endogenous endophthalmitis.

The Clinical Effect of High-Flow Oxygen Therapy through the Nose on Patients with Acute Left Heart Failure and Hypoxemia.

Objective: To evaluate the clinical efficacy of nasal high-flow oxygen therapy in patients with acute left heart failure and hypoxemia. Methods: From July 2016 to November 2018, patients with acute left heart failure complicated with hypoxemia treated in the Department of Critical Medicine of Yantai Affiliated Hospital of Binzhou Medical University were retrospectively observed (a total of 140 cases met the inclusion criteria). They were randomly divided into two groups, with 70 cases in each group. Patients were given continuous ECG monitoring, improved blood gas analysis test, and recorded HR, RR, map, SaO2, pH, PaO2, PaCO2, and Lac, perfect examination and color Doppler echocardiography, and record NT-proBNP and EF before and 24 hours after treatment. The effective rates of the two groups before and after oxygen therapy were detected. Results: There were 67 patients with high-flow oxygen therapy group improvement, 95.7% improvement rate, and 55 patients with general oxygen therapy group improvement rate. The treatment improvement rate was 78.6%. A total of 67 patients were treated with high-flow oxygen therapy. After high-flow oxygen therapy, HR (t = 18.8, P ≤ 0.05), RR (t = 19.7, P ≤ 0.05), MAP (t = 12.1, P ≤ 0.05), PaCO2 (t = 9.53, P ≤ 0.05), Lac (t = 8.69, P ≤ 0.05), and NT-proBNP (t = 7.03, P ≤ 0.05) were significantly lower than before. SaO2 (t = -12.4, P ≤ 0.05), pH (t = -12.2, P ≤ 0.05), PaO2 (t = -17.7, P ≤ 0.05), and EF (t = -13.4, P ≤ 0.05) were significantly higher than before. A total of 55 patients were in the general oxygen therapy group. After administration of ordinary oxygen therapy, HR (t = 18.2, P ≤ 0.05), RR (t = 10.8, P ≤ 0.05), MAP (t = 13.1, P ≤ 0.05), PaCO2 (t = 15.8, P ≤ 0.05), Lac (t = 7.1, P ≤ 0.05), and NT-proBNP (t = 10, P ≤ 0.05) were significantly lower than before. SaO2 (t = -15.5, P ≤ 0.05), pH (t = -4.5, P ≤ 0.05), PaO2 (t = -20, P ≤ 0.05), and EF value (t = -7.7, P ≤ 0.05) were significantly higher than before. Conclusion: High-flow oxygen therapy and general oxygen therapy have an obvious curative effect on patients with acute left heart failure and hypoxemia. Compared with the two, high-flow oxygen therapy is more effective. After high-flow oxygen therapy and general oxygen therapy in patients with acute left heart failure and hypoxia, HR, RR, MAP, SaO2, pH, PaO2, PaCO2, Lac, EF, and NT-proBNP value all improved, and the improvement of high-flow oxygen therapy was greater.

Dynamic changes of scleral spur length in different accommodation stimuli states.

This study aimed to evaluate the scleral spur length (SSL) in response to different accommodation stimuli states, as well as the correlation with Schlemm's canal (SC) and trabecular meshwork (TM). 74 children were recruited for this study. The 0D, - 4D, and - 8.0 D accommodation stimuli state was achieved by looking at a variable distance optotype. The ciliary muscle (CM), scleral spur (SS), SC, and TM were imaged by swept-source optical coherence tomography. The SSL (Method III) increased significantly from 221.56 ± 30.74 µm at base state to 234.99 ± 30.11 µm at - 4D accommodation stimuli state (p = 0.028) and increased to 250.09 ± 29.87 µm at - 8D accommodation stimuli state (p = 0.011). Method III had the largest areas under receiver operating characteristic (ROC) curves (0.798, 95% CI 0.721-0.875). Moreover, CM 1, SC, and trabecular meshwork length (TML) were significantly correlated with SSL (Method III) (p < 0.05). These findings suggest that the contractile ability and compliance of the SS play an important role in maintaining the morphology of the SC. Moreover, the force of accommodation regulates the SC size by increasing the length of SS.