Retinal ischemia-reperfusion injury induces intense lipid synthesis and remodeling.

The retina is a high-metabolism tissue composed of various cell types with complex functions that relies heavily on the blood supply to maintain homeostasis. Retinal ischemia-reperfusion injury is a critical pathogenic mechanism in glaucoma, and changes in lipid molecules may lead to retinal tissue damage. However, retinal lipid profile alterations caused by this mechanism remain unclear. Thus, this study employed a retinal ischemia-reperfusion model to analyze changes in the lipid profile between sham-operated and ischemia-reperfusion groups. We discovered that ischemia-reperfusion injury-induced alterations in 338 lipid molecules, which potentially caused lipid droplet formation and mitochondrial damage. Notably, we identified characteristic changes in various lipids, including cholesterol esters, cardiolipin, and ceramide, which may serve as potential biomarkers for assessing the severity of retinal injury and therapeutic interventions. The ischemia-reperfusion-specific features identified in this study provide a more comprehensive understanding of the pathophysiological mechanisms underlying this condition.

Investigating the Impact of Sun/UV Protection and Ease of Skin Tanning on the Risk of Pseudoexfoliation Glaucoma: A Mendelian Randomization Study.

Purpose: To investigate the potential causal associations between the use of sun/ultraviolet (UV) protection and ease of skin tanning and the risk of pseudoexfoliation glaucoma (PXG) in European populations. Methods: Single nucleotide polymorphisms (SNPs) associated with the use of sun/UV protection and ease of skin tanning were selected from the UK Biobank genome-wide association study database consisting of 498,751 European participants. SNPs of PXG were obtained from the FinnGen study including 3424 PXG cases and 326,434 controls. Two-sample Mendelian randomization (MR) analyses were performed to assess the association between the use of sun/UV protection and ease of skin tanning and risk of PXG. Results: Inverse variance weighted regression of genetic susceptibility predicted that both use of sun/UV protection and ease of skin tanning were potentially positively associated with the decreased risk of PXG in the European ancestry (use of sun/UV protection: odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.24-0.92; P = 0.028; ease of skin tanning: OR = 0.81; 95% CI, 0.67-0.97; P = 0.025). Conclusions: We found genetic evidence supporting a potential causal association between UV protection and a decreased risk of PXG in European population. Further research will help elucidate the underlying mechanisms and promote UV protection for eyes, especially in people with a high risk of PXG.

Using the C-Read as a Portable Device to Evaluate Reading Ability in Young Chinese Adults: An Observational Study.

We evaluated the reading characteristics of normal-sighted young adults using C-Read to provide baseline healthy population values. We also investigated the relationship between the National Eye Institute's Visual Functioning Questionnaire (VFQ-25) score and reading ability, myopia, and hours of screen use, focusing on the extent to which these factors affect participants' visual function and, ultimately, their vision-related quality of life (QoL). Overall, 207 young, healthy participants (414 eyes) aged 18-35 years were tested for reading speed using C-Read connected to a smartphone-based application between December 2022 and January 2023. Each participant received a VFQ-25 questionnaire to evaluate vision-related QoL. Data on daily e-screen usage hours were collected. Among the participants, 91 (44.0%) were women; their mean (SD) age was 22.45 (4.01) years. The mean (SD) reading acuity (RA) was 0.242 (0.124), 0.249 (0.120), and 0.193 (0.104) logarithmic minimum angle of resolution (logMAR) for the right, left, and both eyes, respectively. The mean (SD) maximum reading speed (MRS) was 171.65 (46.27), 168.59 (45.68), and 185.16 (44.93) words per minute (wpm) with the right, left, and both eyes, respectively. The mean (SD) critical print size (CPS) was 0.412 (0.647), 0.371 (0.229), and 0.419 (1.05) logMAR per the right, left, and both eyes, respectively. The RA and CPS were significantly different between sexes (p = 0.002 and p = 0.001). MRS was significantly different between the education level (p = 0.005) and myopia level groups (p = 0.010); however, it was not clear whether this difference was confounded by age. The myopic power in diopters significantly affected RA (coefficient, -0.012; 95% CI, -0.018 to -0.006; p = 0.001); screen time significantly affected MRS (coefficient, 0.019; 95% CI, 0.57 to 6.33; p = 0.019). RA (coefficient, -21.41; 95% CI, -33.74 to -9.08; p = 0.001) and duration of screen use (coefficient, -0.86; 95% CI, -1.29 to -0.43; p < 0.001) independently had a significantly negative correlation with VFQ-25 scores. Our findings provide a baseline value for C-Read in normal-sighted young adults. Refractive status significantly affected RA, while screen time significantly affected MRS. Interventions aimed at enhancing RA may have the potential to maximize vision-related QoL and enable older adults with impaired vision to achieve greater outcomes. Future, larger-scale, C-Read experiments will help provide newer, more optimal methods for the early diagnosis of visual impairment.

Ocular Phenotypes in Patients With Hemophagocytic Lymphohistiocytosis: A Retrospective Analysis in a Single Center Over 7 Years.

PURPOSE: To investigate the presence and type of ocular abnormalities in patients with hemophagocytic lymphohistiocytosis (HLH). DESIGN: A retrospective cross-sectional study. METHODS: Observational report of ocular findings and their associations with age, sex, underlying disease, and hematologic parameters. HLH was defined according to the 2004 criteria, and the patients were enrolled from March 2013 to December 2021. Analysis began in July 2022 and ended in January 2023. The main outcome measures were ocular abnormalities associated with HLH and their potential risk factors. RESULTS: Of 1525 HLH patients, 341 had ocular examinations, and 133 (133 of 341, 39.00%) had ocular abnormalities. Mean age at presentation was 30.21 ± 14.42 years. The multivariate analysis indicated that old age, autoimmune disorders, decreasing red blood cell count, decreasing platelet count, and increasing fibrinogen level were independent risk factors of ocular involvement in HLH patients. The most common presenting ocular findings were posterior segment abnormalities (66 patients, 49.62%), including retinal and vitreous hemorrhage, serous retinal detachment, cytomegalovirus retinitis, and optic disc swelling. Other HLH-associated ocular abnormalities included ocular surface infection (conjunctivitis, 34 patients, 25.56%; keratitis, 16 patients, 12.03%), subconjunctival hemorrhage (11 patients, 8.27%), chemosis (5 patients, 3.76%), anterior uveitis (11 patients, 8.27%), glucocorticoid-induced glaucoma (5 patients, 3.76%), radiation cataract (1 patient, 0.75%), dacryoadenitis (2 patients, 1.50%), dacryocystitis (1 patients, 0.75%), orbital cellulitis (2 patients, 1.50%), orbital pseudotumor (2 patients, 1.50%), and strabismus (2 patients, 1.50%). CONCLUSIONS: Eye involvement is not uncommon in HLH. Better awareness among both ophthalmologists and hematologists is necessary for prompt diagnosis and institution of appropriate management strategies with potential to save sight and life.

Trends in operating room-based glaucoma procedures at a single eye center from 2016-2020.

AIM: To evaluate trends in glaucoma procedures at the Peking University Eye Center in 2016-2020. METHODS: A retrospective search of all glaucoma procedures performed at our institution were performed. Data were analyzed by calculating the absolute numbers and relative weightage of each procedure per year. RESULTS: The average age of glaucoma patients undergoing surgical procedures was 62.33±17.87y, and 55% were women. From 2016 to 2019, the number of surgical procedures performed in glaucoma patients showed an overall upward trend from 749 to 1460, although it decreased slightly in 2020 (n=1393), probably due to the COVID-19 pandemic. The number of trabeculectomies did not change significantly in 2016 (n=161) to 2018 (n=164) but decreased in 2019 (n=139) to 2020 (n=121), indicating a reduction in its relative weightage among glaucoma procedures (from 21.50% to 8.69%). The number of glaucoma drainage device implantations and minimally invasive glaucoma surgeries both increased (50 and 58 respectively in 2019), except in 2020. The number of transscleral cyclophotocoagulation procedures was relatively stable, increasing until 2017 (n=218) and then decreasing. Cataract surgeries with or without glaucoma procedures accounted for a large number of the total surgeries, increasing from 247 (32.97%) in 2016 to 967 (69.42%), among which cataract extraction combined with goniosynechialysis was the most frequent. CONCLUSION: The overall increase in the number of operating room-based surgical procedures is significant. Trabeculectomy is one of the most commonly performed procedures, despite the relative decline in its weightage. Other procedures, including use of glaucoma drainage devices and mini shunts and minimally invasive glaucoma surgeries, are gaining greater acceptance. Notably, lens-related surgery plays an important role in glaucoma management.

Screening of primary open-angle glaucoma diagnostic markers based on immune-related genes and immune infiltration.

PURPOSE: Primary open-angle glaucoma (POAG) continues to be a poorly understood disease. Although there were multiple researches on the identification of POAG biomarkers, few studies systematically revealed the immune-related cells and immune infiltration of POAG. Bioinformatics analyses of optic nerve (ON) and trabecular meshwork (TM) gene expression data were performed to further elucidate the immune-related genes of POAG and identify candidate target genes for treatment. METHODS: We performed a gene analysis of publicly available microarray data, namely, the GSE27276-GPL2507, GSE2378-GPL8300, GSE9944-GPL8300, and GSE9944-GPL571 datasets from the Gene Expression Omnibus database. The obtained datasets were used as input for parallel pathway analyses. Based on random forest and support vector machine (SVM) analysis to screen the key genes, significantly changed pathways were clustered into functional categories, and the results were further investigated. CIBERSORT was used to evaluate the infiltration of immune cells in POAG tissues. A network visualizing the differences between the data in the POAG and normal groups was created. GO and KEGG enrichment analyses were performed using the Metascape database. We divided the differentially expressed mRNAs into upregulated and downregulated groups and predicted the drug targets of the differentially expressed genes through the Connectivity Map (CMap) database. RESULTS: A total of 49 differentially expressed genes, including 19 downregulated genes and 30 upregulated genes, were detected. Five genes ((Keratin 14) KRT14, (Hemoglobin subunit beta) HBB, (Acyl-CoA Oxidase 2) ACOX2, (Hephaestin) HEPH and Keratin 13 (KRT13)) were significantly changed. The results showed that the expression profiles of drug disturbances, including those for avrainvillamide-analysis-3, cytochalasin-D, NPI-2358, oxymethylone and vinorelbine, were negatively correlated with the expression profiles of disease disturbances. This finding indicated that these drugs may reduce or even reverse the POAG disease state. CONCLUSION: This study provides an overview of the processes involved in the molecular pathogenesis of POAG in the ON and TM. The findings provide a new understanding of the molecular mechanism of POAG from the perspective of immunology.

Proteomics analysis of N-methyl-d-aspartate-induced cell death in retinal and optic nerves.

This study aimed to comprehensively understand the proteomic characteristics and modulation of the neural microenvironment with N-methyl-d-aspartate (NMDA)-induced neuronal degeneration in the retina and optic nerve at 12 h after intravitreal injection of 40 nmol NMDA. Male Sprague-Dawley rats were sacrificed at 12 h after intravitreal injection of 40 nmol NMDA. PBS-injected eyes served as controls. The key cell death-linked proteins from the retina and optic nerve tissues were assessed by a mass spectrometry-based label-free approach. In proteomics analysis, we identified 3532 proteins in retinal tissues and 2593 proteins in optic nerve tissues. The ACSL3 (Q63151) and Prnp (P13852) proteins were upregulated in the NMDA-damaged retina and connected with ferroptosis. The Gabarapl2 (P60522) protein was upregulated in NMDA-damaged optic nerves and connected with autophagy. We performed parallel reaction monitoring (PRM) to validate the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results. Data are available ProteomeXchange with identifiers PXD022466 (label-free quantification) and PXD022729 (PRM validation). SIGNIFICANCE: Excitotoxicity is one of the pathogeneses of various retinal disorders, including glaucoma, retinal ischemia-reperfusion and traumatic optic neuropathy. This study indicated that ferroptosis may be linked to pathological cell death in the retina with NMDA insult. Autophagy may be induced by NMDA overstimulation in both the optic nerve and retina. Regulating these types of death simultaneously may provide the maximum benefit for retinal disease therapy.

Use of Mobile Apps for Visual Acuity Assessment: Systematic Review and Meta-analysis.

BACKGROUND: Vision impairments (VIs) and blindness are major global public health issues. A visual acuity (VA) test is one of the most crucial standard psychophysical tests of visual function and has been widely used in a broad range of health care domains, especially in many clinical settings. In recent years, there has been increasing research on mobile app-based VA assessment designed to allow people to test their VA at any time and any location. OBJECTIVE: The goal of the review was to assess the accuracy and reliability of using mobile VA measurement apps. METHODS: We searched PubMed, Embase, Cochrane Library, and Google Scholar for relevant articles on mobile apps for VA assessment published between January 1, 2008, and July 1, 2020. Two researchers independently inspected and selected relevant studies. Eventually, we included 22 studies that assessed tablet or smartphone apps for VA measurement. We then analyzed sensitivity, specificity, and accuracy in the 6 papers we found through a meta-analysis. RESULTS: Most of the 22 selected studies can be considered of high quality based on the Quality Assessment of Diagnostic Accuracy Studies-2. In a meta-analysis of 6 studies involving 24,284 participants, we categorized the studies based on the age groups of the study participants (ie, aged 3-5 years, aged 6-22 years, and aged 55 years and older), examiner (ie, professional and nonprofessional examiners), and the type of mobile devices (ie, smartphone, iPad). In the group aged 3 to 5 years, the pooled sensitivity for VA app tests versus clinical VA tests was 0.87 (95% CI 0.79-0.93; P=.39), and the pooled specificity was 0.78 (95% CI 0.70-0.85; P=.37). In the group aged 6 to 22 years, the pooled sensitivity for VA app tests versus clinical VA tests was 0.86 (95% CI 0.84-0.87; P<.001), and the pooled specificity for VA app tests versus clinical VA tests was 0.91 (95% CI 0.90-0.91; P=.27). In the group aged 55 years and older, the pooled sensitivity for VA app tests versus clinical VA tests was 0.85 (95% CI 0.55-0.98), and the pooled specificity for VA app tests versus clinical VA tests was 0.98 (95% CI 0.95-0.99). We found that the nonprofessional examiner group (AUC 0.93) had higher accuracy than the professional examiner group (AUC 0.87). In the iPad-based group, the pooled sensitivity for VA app tests versus clinical VA tests was 0.86, and the pooled specificity was 0.79. In the smartphone-based group, the pooled sensitivity for VA app tests versus clinical VA tests was 0.86 (P<.001), and the pooled specificity for VA app tests versus clinical VA tests was 0.91 (P<.001). CONCLUSIONS: In this study, we conducted a comprehensive review of the research on existing mobile apps for VA tests to investigate their diagnostic value and limitations. Evidence gained from this study suggests that mobile app-based VA tests can be useful for on-demand VI detection.

Decreased expression of TIPE2 in the eye under high-glucose conditions tested in vivo and in vitro.

AIMS: Inflammation is important in the development of angiogenesis diabetic retinopathy (DR). Anti-inflammation is promising strategy in early DR management. This study aimed to evaluate the level of tumour necrosis factor (TNF)-α-induced protein-8 like-2 (TIPE2), a formerly anti-inflammatory factor, under high-glucose conditions. METHODS: TIPE2 was detected in the ① retina from db/db and streptozotocin-induced diabetic mice; ② vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and ③ mouse retinal microendothelial cells (RMEC) cultured in glucose of varying concentrations. In situ expression was evaluated by immunohistochemistry and immunofluorescence assay. The expression of protein was analysed by Western blot or ELISA and mRNA by qRT-PCR. RESULTS: TIPE2 was down-regulated in the retina of the mice with diabetes. TIPE2 was present in the cytoplasm of RMEC and down-regulated in high-glucose conditions in line with concentration and time. The expression of TIPE2 in the vitreous fluid of patients with PDR was significantly lower than that without diabetes. Silencing TIPE2 by an siRNA resulted in increased expression of vascular endothelial growth factor (a vital factor in the development of DR), TNF-α and IL-1ß. CONCLUSIONS: TIPE2 down-expressed and exerted anti-VEGF and anti-inflammatory function in the high-glucose environment. TIPE2 was verified to be involved in the process of DR and might be a potential regulator for DR development.

Low-Dose Aspirin Prevents Kidney Damage in LPS-Induced Preeclampsia by Inhibiting the WNT5A and NF-κB Signaling Pathways.

Preeclampsia (PE) is a serious pregnancy-related disease, and patients usually present with a high inflammatory response. Previous studies have suggested that aspirin (ASP) may have a role in alleviating the pathogenesis of preeclampsia. However, whether ASP can improve kidney damage and the mechanism for improving it is currently unclear. Here we optimized a lipopolysaccharide (LPS)-induced PE mouse model to identify the role of ASP in renal protection. We found that ASP treatment ameliorated LPS-induced renal failure and pathological changes, the tubular injury was significantly attenuated by ASP. Administration of ASP decreased the renal expression of pro-inflammatory factors, resulting in reduced kidney inflammation. The number of GALECTIN-3-positive cells was reduced, and the up-regulation of IL-6 and TNF-α was decreased. In addition, ASP also suppressed renal cell apoptosis and oxidative stress. An in vitro study indicated that ASP relieved LPS-induced HK-2 cell damage by inhibiting WNT5A/NF-κB signaling. Collectively, our data suggest that ASP is a useful therapeutic option for PE-related kidney injury.

Safety and Efficacy of Bleb Needling with Antimetabolite after Trabeculectomy Failure in Glaucoma Patients: A Systemic Review and Meta-Analysis.

BACKGROUND: Bleb needling with subconjunctival injection of antimetabolites had become a widely accepted approach for trabeculectomy failure. However, IOP reduction effects, success rates, and complications occurrence for this procedure showed great inconsistency among the different studies. METHODS: We conducted a literature search on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. A random-effects model was performed on the extracted data based on the included studies. The intraocular pressure (IOP) and number of antiglaucomatous medications before and after the surgery were pooled for meta-analysis. The success and complication rates were estimated based on the results. Subgroup analysis, sensitivity analysis, and metaregression were applied to explore the origination of heterogeneity. RESULTS: Thirty-seven studies with a total of 2182 patients were finally included in our review. For the present meta-analysis, the overall effects of bleb needling at the last visit revealed a reduction in IOP of 9.74 mmHg (95% confidence interval (CI) [8.85, 10.63]), 45.9% (95% CI [39.0%, 53.0%]) for complete success rate, and 70.4% (95% CI [63.5%, 77.0%]) for qualified success rate. Application of mitomycin C (MMC) and 5-fluorouracil (5-Fu) during the procedure were efficacious for IOP control during the follow-up. Metaregression revealed that possible origination of heterogeneity was baseline IOP before bleb needling, revealing a trend that higher baseline IOP correlated with a greater IOP reduction results (p < 0.001). For safety profile, conjunctival haemorrhage (5.7%, 95% CI [2.5%, 10.1%]), hyphema (5.5%, 95% CI [3.0%, 8.7%]), and bleb leakage (5.0%, 95% CI [3.2%, 7.3%]) had the highest estimate of incidence. An increasing number of needling was the main risk factor for needling failure. CONCLUSION: Bleb needling with antimetabolites could be considered an effective and safe procedure after trabeculectomy failure. After the process, patients will gain IOP control and reduce antiglaucomatous medications for at least six months with 5-Fu or MMC. Meanwhile, the overall estimates for complications were relatively low in the whole process.

Evaluating State-of-the-Art Computerized Pupillary Assessments for Glaucoma Detection: A Systematic Review and Meta-Analysis.

Computerized pupillary light reflex assessment devices (CPLRADs) may serve as an effective screening tool for glaucomatous optic neuropathy, since they can dynamically detect abnormal pupillary responses from a novel sequence of light stimuli and functionally-shaped stimuli. The aim of this study was to systematically evaluate the current state of advanced CPLRADs and accuracy of application in detecting glaucoma. An electronic literature search of PubMed, MEDLINE, and Embase from database inception to December 2019 was performed. Studies that reported data on the use of computer-aided pupillometry with monocular and/or binocular monitoring in glaucoma patients were included. Two review authors independently conducted the study selection and extracted study data. A total of twenty-five studies were included in this review; eight studies with a total of 829 subjects were included in this meta-analysis. Data were pooled using a random-effect model, since the significant heterogeneity (P < 0.1, I 2> 50%). Our meta-analysis of eight studies showed reasonably high summary sensitivity and specificity estimates of 0.81 (95% CI 0.73-0.89) and 0.83 (95% CI: 0.75-0.91), respectively. Simpler monochromatic devices, such as PupilmetrixTM PLR60, generally performed as well as or slightly better than more complex chromatic devices. This review suggests that CPLRADs may facilitate direct clinical decision making for glaucoma diagnosis and evaluation, and may provide a deeper understanding of the pathomechanism of glaucoma.

Anti-inflammatory TIPE2 inhibits angiogenic VEGF in retinal pigment epithelium.

Choroidal neovascularization (CNV) is a pathological feature which commonly occurs in ocular diseases. This condition is characterised by vasculogenesis and angiogenesis underlying the neuroretina, with retinal pigment epithelium (RPE) and choroid as main targets. Inflammation and immunity are crucial in the early development of CNV. Tumour necrosis factor (TNF) α-induced protein-8 like-2 (TIPE2 or TNFAIP8L2), a recently identified gene, is a negative regulator of innate and adaptive immunity which participates in inflammatory homeostasis. We determined the expression of TIPE2 in normal and inflamed RPE cells, and evaluated the relationship of TIPE2 with factors associated with inflammation and angiogenesis. TIPE2 is present in both the cytoplasm and nucleus of human RPE cells and is down-regulated in the inflammatory state with decreased cell viability. Knock-down of TIPE2 by a specific short interfering RNA increases the expression levels of TNF-α, IL-1ß and angiogenic vascular endothelial growth factor (VEGF), particularly under the stimulation of lipopolysaccharide. In consideration of the vital role of VEGF in the final stage of neovascularization, the anti-inflammatory TIPE2 is also anti-angiogenic and may participate in CNV formation.