Potential Immune-Inflammatory Proteome Biomarkers for Guiding the Treatment of Patients with Primary Acute Angle-Closure Glaucoma Caused by COVID-19.

Primary acute angle-closure glaucoma (PAACG) is a sight-threatening condition that can lead to blindness. With the increasing incidence of COVID-19, a multitude of people are experiencing acute vision loss and severe swelling of the eyes and head. These patients were then diagnosed with acute angle closure, with or without a history of PACG. However, the mechanism by which viral infection causes PACG has not been clarified. This is the first study to explore the specific inflammatory proteomic landscape in SARS-CoV-2-induced PAACG. The expression of 92 inflammation-related proteins in 19 aqueous humor samples from PAACGs or cataract patients was detected using the Olink Target 96 Inflammation Panel based on a highly sensitive and specific proximity extension assay technology. The results showed that 76 proteins were significantly more abundant in the PAACG group than in the cataract group. Notably, the top eight differentially expressed proteins were IL-8, MCP-1, TNFRSF9, DNER, CCL4, Flt3L, CXCL10, and CD40. Generally, immune markers are related to inflammation, macrophage activation, and viral infection, revealing the crucial role of macrophages in the occurrence of PAACGs caused by SARS-CoV-2.

Sildenafil-induced bilateral ciliochoroidal effusion syndrome: Case report.

PURPOSE: To report a case of bilateral ciliochoroidal effusion syndrome associated with sildenafil use. CASE REPORT: A 41-year-old male presented with a five-day history of bilateral blurred vision, elevated intraocular pressure, and myopic shift. Ultrasound biomicroscopy radial scans showed closed angles and 360 degrees of ciliochoroidal effusion in both eyes. Anterior segment coherence tomography angiography showed bilateral shallow anterior chamber. Further questioning revealed that the patient had taken sildenafil several times just a few days before symptoms appeared. Since then, the patient stopped dosing sildenafil. After treatment of anti-inflammation and shifting the lens-iris diaphragm posteriorly, the patient's visual acuity improved and intraocular pressure decreased. Follow-up ultrasound biomicroscopy and anterior segment coherence tomography angiography revealed resolution of ciliochoroidal effusion and increase of anterior chamber depth in both eyes. CONCLUSIONS: The patient demonstrated a rare case of sildenafil-induced bilateral ciliochoroidal effusion syndrome. This case report shows that sildenafil should be added to the possible causative agents of ciliochoroidal effusion syndrome.

Aqueous Humor Growth Factor Levels and Trabeculectomy Outcomes in Primary Open-Angle Glaucoma Patients: A 2-Year Prospective Study.

Purpose: Maintenance of a filtering bleb is essential for long-term intraocular pressure control after trabeculectomy. Surgical site fibrosis and excessive extracellular matrix production are common causes of trabeculectomy failure, mediated by several growth factors. We aimed to evaluate the levels of five growth factors and their correlation with trabeculectomy outcomes in patients with primary open-angle glaucoma (POAG). Methods: We collected aqueous humor samples intraoperatively from patients with POAG who underwent trabeculectomy and measured the concentrations of transforming growth factor-ß (TGF-ß), acidic fibroblast growth factor (aFGF), insulin-like growth factor-1, vascular endothelial growth factor, and platelet-derived growth factor using multiplexed immunoassay kits. Intraocular pressure was measured with Goldmann applanation tonometry at 1 week and at 1, 3, 6, 12, 18, and 24 months after trabeculectomy. We allocated the eyes based on surgical outcome into a success or failure group. Results: Significantly high levels of aFGF and TGF-ß were observed in the failure group (both P < 0.0001) and were significant risk factors for trabeculectomy outcomes. Higher success rates were observed over the 24-month follow-up period in eyes with low aFGF and TGF-ß levels compared to eyes with high levels (P = 0.0031 and P = 0.0007, respectively). The levels of TGF-ß were significantly positively correlated with aFGF. Conclusions: In POAG patients, high aFGF and TGF-ß levels were significant risk factors for trabeculectomy failure. Translational Relevance: Modulation of aFGF and TGF-ß expression may have potential clinical applications after filtration surgery.

Potential effects of angiogenesis-related factors on the severity of APAC and surgical outcomes of trabeculectomy.

BACKGROUND: EPO (erythropoietin) and PDGF (platelet derived growth factor) families are thought to be associated with angiogenesis under hypoxic condition. The sharp rise of intraocular pressure in acute primary angle closure (APAC) results in an inefficient supply of oxygen and nutrients. We aimed to measure the expression of EPO and PDGF family members in APAC eyes and demonstrate their associations with APAC's surgical success rate. METHODS: Concentrations of EPO, PDGF-AA, -BB, -CC and -DD collected in aqueous humor samples of 55 patients recruited were measured. Before operations, correlations between target proteins and IOP (intraocular pressure) were detected between APAC (acute primary angle closure) and cataract patients. Based on the post-operative follow-up, the effects of EPO and PDGF family members on the successful rate of trabeculectomy were tested. RESULTS: The levels of EPO, PDGF-CC and -DD were significantly elevated in the APAC group compared to the cataract group. During the post-operative follow-up, EPO, PDGF-CC and -DD showed significant differences between the success and failure groups. In multivariable linear regression analyses, failed filtration surgery was more likely in APAC eyes with higher EPO level. The Kaplan-Meier survival plot suggested that the success rate in eyes with low EPO level was significantly higher than that in eyes with high EPO level. CONCLUSION: The levels of EPO, PDGF-CC and -DD were significantly elevated in failure group. EPO level correlated with preoperative IOP and numbers of eyedrops, and higher EPO level in aqueous humor is a risk factor for trabeculectomy failure. It can be a biomarker to estimate the severity of APAC and the success rate of surgery. The investigation of mechanism of EPO in APAC a may have potential clinical applications for the surgical treatment of APAC.

Agreement of Optic Nerve Head Evaluation of Primary Open-Angle Glaucoma Between General Ophthalmologists and Glaucoma Specialists.

PURPOSE: To investigate the agreement of optic nerve head evaluations and initial diagnoses of primary open-angle glaucoma (POAG) by general ophthalmologists and glaucoma specialists in Shanghai, China. METHODS: This multicenter, cross-sectional study involved the outpatients from the general ophthalmology departments of four top eye hospitals in Shanghai. The participants underwent ocular examinations, including intraocular pressure, fundus photography, corneal thickness, refractometry, visual acuity, visual field and gonioscopy. General ophthalmologists and glaucoma specialists performed the diagnoses and classified them as non-glaucoma, POAG suspects, and POAG. The consistency of initial diagnosis between general ophthalmologists and glaucoma specialists was measured using the weighted kappa coefficient. Logistic regression analysis was used to detect the risk factors for the reliability of POAG diagnosis. RESULTS: In 922 participants, the initial diagnosis rates of POAG and non-glaucoma were much higher in the glaucoma specialist group than in the general ophthalmologist group, while the initial diagnosis rates of POAG suspects were higher in the general ophthalmologist group. The weighted kappa coefficient between the two groups was 0.831±0.027 (95% confidence interval, 0.779-0.884). Logistic regression analysis of the risk factors for the reliability of POAG diagnosis showed that the independent risk factors were intraocular pressure (OR 8.363, 95% CI: 4.27-16.37) and vertical cup-to-disc ratio (OR 3.459, 95% CI: 1.54-7.76). CONCLUSION: The diagnosis consistency between the general ophthalmologists and the glaucoma specialists was similar among outpatients in the area of Shanghai. However, general ophthalmologists tended to classify the indefinite subjects as POAG suspects, and their accuracy in diagnosing POAG was low. By paying more attention to the risk factors of POAG diagnosis, general ophthalmologists could improve the diagnosis accuracy.

Inflammatory cytokines levels in aqueous humour and surgical outcomes of trabeculectomy in patients with prior acute primary angle closure.

PURPOSE: To quantify the levels of three inflammatory cytokines in the aqueous humour of patients with prior acute primary angle closure (APAC) and investigate their correlation with surgical outcomes of trabeculectomy. METHODS: In this prospective cohort study, aqueous humour samples were collected from 44 prior APAC eyes. Analyte concentrations of monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured using multiplexed immunoassay kits. Intraocular pressure was measured using Goldmann application tonometry. RESULTS: Forty-four prior APAC eyes were followed up for 24 months after trabeculectomy and divided into success and failure groups according to surgical outcomes. Monocyte chemoattractant protein-1 (MCP-1) levels in the aqueous humour were significantly higher in the failure group (p = 0.0118). Univariate and multivariate analyses showed that MCP-1 level was a significant risk factor for trabeculectomy outcomes (univariate analysis: p = 0.016, odds ratio = 14.538; multivariate analysis: p = 0.023, odds ratio = 13.718). When prior APAC eyes were divided according to MCP-1 levels, the overall success rate was significantly higher in eyes with low MCP-1 levels than eyes with high MCP-1 levels (p = 0.0249). CONCLUSION: In prior APAC patients, the MCP-1 level in the aqueous humour predicts trabeculectomy results. Therefore, modulation of MCP-1 expression may have potential clinical applications after filtration surgery.

Changes in Intraocular Pressure and Angle Structure after Dilation in Primary Angle-Closure Suspects with Visually Significant Cataract.

PURPOSE: To evaluate the safety of pupillary dilation in primary angle-closure suspects (PACS) with concurrent visually significant cataract (VSC), to identify risk factors associated with elevated intraocular pressure (IOP), and to describe changes in anterior segment anatomy after pupillary dilation. DESIGN: Prospective study. PARTICIPANTS: Patients with PACS and VSC and no prior laser or intraocular surgery were recruited. Visually significant cataract was defined as best-corrected visual acuity ≤ 20/40 due to cataract. METHODS: Subjects' eyes were dilated with 0.5% tropicamide and 0.5% phenylephrine hydrochloride. A standardized eye examination, biometry, and swept-source OCT (SS-OCT) were performed before dilation. Intraocular pressure and SS-OCT were repeated 1, 4, and 6 hours postdilation (PDH1, PDH4, and PDH6, respectively). All parameters were compared between time points before and after dilation using paired t test. Linear regression models were used to determine the risk factors associated with postdilation IOP changes. MAIN OUTCOME MEASURES: Change in IOP and SS-OCT parameters from baseline. RESULTS: Seventy-eight eyes from 78 patients were included, with 78, 66, and 12 patients completing the study at PDH1, PDH4, and PDH6, respectively. Mean IOP increased from 14.8 ± 2.6 mmHg at baseline to 15.5 ± 3.5 mmHg at PDH1 (P = 0.03) and decreased to 14.9 ± 3.1 mmHg at PDH4 (P = 0.09). Four patients (5.13%) and 3 patients (3.85%) had an increase in IOP ≥ 5 mmHg at PDH1 and PDH4, respectively. Two patients (2.56%) and 1 patient (1.28%) had an increase in IOP ≥ 8 mmHg at PDH1 and PDH4, respectively. None developed acute primary angle-closure during the observation period. Almost all anterior chamber parameters showed a significant increase after dilation at PDH1 and PDH4, except lens vault and iris volume, which decreased at PDH1 and PDH4 from baseline. Increase in anterior chamber depth was negatively associated with the level of IOP elevation after dilation (P < 0.01). CONCLUSIONS: Dilation of patients' eyes with PACS and VSC in this cohort appears to have a low risk for IOP spike. This may be associated with relaxation of the ciliary muscle leading to posterior displacement of the lens-iris diaphragm and deepening of the anterior chamber.

Identification of lncRNA-miRNA-mRNA regulatory network associated with primary open angle glaucoma.

BACKGROUND: Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. METHODS: Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. RESULTS: During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. CONCLUSION: This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

Imbalance of Matrix Metalloproteinases and Their Inhibitors Is Correlated With Trabeculectomy Outcomes in Acute Primary Angle Closure.

PURPOSE: To analyze matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and their molar ratios in the aqueous humor in previous acute primary angle closure (APAC) patients and their correlations with trabeculectomy outcomes. DESIGN: Prospective cohort study. METHODS: Aqueous humor samples were collected from a total of 78 eyes, including 52 previous APAC eyes and 26 cataract eyes. TIMP-1, 2, 3, and 4 and MMP-1, 2, 3, 7, 8, 9, 12, and 13 analyte concentrations were measured using multiplexed immunoassay kits. Patient follow-up occurred at 1 week and 1, 3, 6, 12, and 18 months. RESULTS: In the previous APAC group, 11 MMP/TIMP molar ratios were significantly lower. APAC eyes were then followed for up to 18 months after trabeculectomy and divided into success (37 eyes) and failure (15 eyes) groups. Five out of the 11 molar ratios were significantly lower in the failure group than in the success group. In multiple logistic regression analysis, failed filtration surgery was more likely in APAC eyes with lower MMP-2/TIMP-2 (P = .040, odds ratio = 44.499) and MMP-13/TIMP-1 (P = .034, odds ratio = 37.947) ratios. Previous APAC eyes were divided according to MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios. Compared to eyes with high ratios, eyes with low MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios had significantly higher failure rates. CONCLUSIONS: In previous APAC eyes, changes in MMP and TIMP levels resulted in MMP and TIMP imbalance. Lower MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios in aqueous humor are risk factors for trabeculectomy failure. Modulating specific MMP/TIMP ratios may have potential clinical applications for filtration surgery.

Matricellular Protein Levels in Aqueous Humor and Surgical Outcomes of Trabeculectomy.

Purpose: The purpose of this study was to quantify levels of three matricellular proteins in the aqueous humor in patients with previous acute primary angle closure (APAC) and investigate their correlation with bleb morphology and surgical outcomes of trabeculectomy. Methods: In this prospective study, aqueous humor samples were collected from 40 previous APAC eyes. Concentrations of three matricellular proteins-secreted protein acidic and rich in cysteine (SPARC), thrombospondin-2, and osteopontin-were measured using multiplexed immunoassays kits. Intraocular pressure was measured using Goldmann application tonometry. Bleb morphology was assessed using anterior segment optical coherence tomography, and bleb score was calculated according to bleb size and reflectivity. Results: When previous APAC eyes were divided according to surgical outcome 18 months after trabeculectomy, SPARC protein was significantly higher in aqueous humor in the failure group (P = 0.009). When previous APAC eyes were divided according to SPARC level, eyes with low SPARC levels had significantly higher overall success rate compared with eyes with high SPARC levels (P = 0.005 for complete success and P = 0.018 for qualified success). Multiple logistic regression analyses showed that eyes with higher levels of SPARC were more likely to have a failed filtration surgery than were eyes with lower levels of SPARC. For complete success, P = 0.006 and odds ratio (OR) = 6.458; for qualified success, P = 0.033 and OR = 2.608. The level of SPARC was found to have a positive correlation with bleb score (P < 0.001, R2 = 0.471). Conclusions: In previous APAC patients, the SPARC level in aqueous humor is a prognostic factor for surgical results of trabeculectomy. Modulation of SPARC expression may have potential clinical applications after filtration surgery.

Matricellular Proteins Play a Potential Role in Acute Primary Angle Closure.

PURPOSE: To quantify levels of matricellular proteins in aqueous humor samples from acute primary angle closure (APAC) and non-glaucomatous cataract eyes and investigate their correlation with intraocular pressure (IOP) fluctuation. MATERIALS AND METHODS: Aqueous humor samples were collected from 63 eyes including 29 current APAC eyes, 12 previous APAC eyes, and 22 cataract eyes. Concentrations of four main matricellular proteins (SPARC, tenascin-C, thrombospondin-2, and osteopontin) were measured using multiplexed immunoassay kits. Correlations between matricellular proteins and age, sex, and IOP were then detected using Spearman's rank correlation coefficient. RESULTS: The levels of SPARC, thrombospondin-2, and osteopontin were significantly elevated in the APAC group as compared to the cataract group (p < 0.001, p < 0.001, and p = 0.009, respectively). Further separation of the APAC group into current and previous APAC groups showed that only the differences of SPARC and thrombospondin-2 between the current APAC and cataract groups were significant (both p < 0.001). All four matricellular proteins were found to have a positive correlation with IOP in the current APAC group but no correlation was found in the previous APAC or cataract groups. CONCLUSIONS: The levels of matricellular proteins were significantly elevated in the current APAC eyes and positively correlated to IOP. Further studies are necessary to investigate the molecular mechanisms and histological evidence of pathogenesis in matricellular proteins in APAC.

The role of induced pluripotent stem cell (IPs) in the transplantation of glaucoma.

AIM: Glaucoma is a heterogeneous group of optic diseases that affect almost 1% to 2% of the population older than 40 years. There are many types of glaucoma but the most common type is primary open angle glaucoma. In this study we have investigated the role of muller cell lines in the transplantation of glaucoma model in rats. METHODS: Intra ocular pressure was created with the help of laser treatment in rats. The induced pluripotent stem cells (IPs) were transplanted into the vitreous or sub-retinal space of glaucomatous or untreated eyes. Double therapy was used for the prevention of graft rejection. The rats were served with the mixture of two drugs in the drinking water. For this purpose cyclosporine (20mg/kg/ day) and azathioprine (2mg/kg/day) were used. This drug therapy started three days before induction of glaucoma. RESULTS: The transplanted cells were survived in vivo for 2 to 3 weeks and reduction in graft survival was also seen at the 4th week. Immunohistochemical analysis showed that a large number of oligodendrocyte precursor cells (OPCs), positive for the nuclear marker Olig2, survived in the vitreous, proximal to the inner surface of the retina, in glaucomatous eye for up to four weeks. CONCLUSION: Differentiating IPs cells within the glaucomatous eye produced cells that expressed glial cell markers.

[The efficacy of low-energy selective laser trabeculoplasty].

OBJECTIVE: To evaluate the efficacy of low-energy selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT) following up to one year. METHODS: In this prospective clinical study, seventy-four eyes of seventy-four patients with OHT and POAG were enrolled. Thirty-nine patients received low-energy treatment using half of conventional laser energy and 100 spots over 360° of the trabecular meshwork, while thirty-five patients received conventional laser energy as control. Intraocular pressure (IOP) and complications including conjunctival hyperemia and anterior uveitis were followed up at week 2, and month 1, 3, 6, and 12. Effective rate (reduction of IOP ≥ 20%) of treatment between the two groups and total rate of complications were analyzed by the chi-squared test. RESULTS: In OHT group, the effective rates of treatment were 81.81(9/11), 63.63 (7/11), 63.63 (7/11), 63.63 (7/11), and 45.45% (5/11) in the low-energy group and 50.00 (5/10), 70.0 (7/10), 60.0 (6/10), 40.0 (4/10), and 50.0% (5/10) in the control group, at weeks 2, month 1, 3, 6, and 12 after treatment respectively, while in POAG, the effective rates were 83.33 (15/18), 88.88 (16/18), 72.22 (13/18), 66.66 (12/18), and 44.44% (8/18) in the low-energy group and 84.21 (16/19), 73.68 (14/14), 57.89 (11/19), 57.89 (11/19) and 47.37% (9/19) in the control group at weeks 2, month 1, 3, 6, and 12 after treatment, respectively. There were no statistical difference between the low energy and conventional energy group at all time points in OHT (χ(2) = 2.386, 0.096, 1.173, 1.110, 0.043) and POAG (χ(2) = 0.005, 1.393, 0.833, 0.302, 0.032) group (P > 0.05). Complications were significantly (χ(2) = 4.299, P < 0.05) different between the two groups (eight eyes in the low-energy group on the day of treatment and fifteen eyes in the control group). Transient IOP spike (≥ 3 mm Hg, 1 mm Hg = 0.133 kPa) occurred in three eyes (in the control group) on the day of treatment and partial peripheral anterior synechiae in one eye (in the control group) one month after treatment. CONCLUSIONS: Low-energy SLT is as effective in lowering IOP with less complications compared with conventional laser energy SLT, which can be considered as an option for glaucoma therapy.

The efficacy of low-energy selective laser trabeculoplasty.

BACKGROUND AND OBJECTIVE: to analyze the efficacy of low-energy selective laser trabeculoplasty (SLT) in patients. PATIENTS AND METHODS: in 74 patients (74 eyes) with ocular hypertension, suspected glaucoma, or primary open-angle glaucoma, SLT was the first-choice treatment. Thirty-nine patients in the low-energy group received treatment using half of conventional laser energy over 360° of the trabecular meshwork (at 100 points). Thirty-five patients in the control group received conventional laser energy. Patients were observed for 1 year. Complications and intraocular pressure (IOP) were observed. RESULTS: postoperative transient IOP spike (≥ 3 mm Hg) occurred in three eyes on the day of treatment and partial peripheral anterior synechiae occurred in one eye 1 month after treatment only in the control group. Effective rates of treatment (≥ 20% IOP reduction) at week 2 and month 1, 3, 6, and 12 after treatment were 69.23%, 64.10%, 61.54%, 53.85%, and 48.72% in the low-energy group and 71.43%, 71.43%, 60%, 51.43%, and 48.57% in the control group, respectively. There was no statistically significant difference between the two groups at various time points (P = .836, .501, .892, .835, .990). CONCLUSION: compared with SLT using conventional laser energy, low-energy SLT lowers IOP with fewer complications, making it a safe and effective option.