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Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).

Background: Glaucoma is a multifactorial optic neuropathy and the leading cause of irreversible blindness worldwide. Vascular mechanisms, including impaired perfusion of the optic nerve head, are increasingly recognized as contributors to disease progression. Optical coherence tomography angiography (OCTA) enables non-invasive assessment of retinal and choroidal microvasculature, including peripapillary microvasculature dropout (MvD), which may serve as a marker of glaucomatous damage. Methods: A cross-sectional case–control study was conducted, including patients with primary open-angle glaucoma (OAG) and healthy controls. All participants underwent a comprehensive ophthalmic evaluation and OCTA imaging using the PLEX Elite 9000 system. Peripapillary vessel density (pVD), flow index (pFI), peripapillary choroidal thickness (PCT), β-zone parapapillary atrophy (β-PPA), and choroidal vascular indices were measured. MvD was defined as the complete absence of microvasculature within the β-PPA boundary. Statistical analyses included univariate and multivariate regression models to examine variables associated with PCT and to assess the association between MvD and visual field mean defect (MD), as well as other glaucoma characteristics. ROC curve analysis was performed to evaluate the ability of MvD to discriminate between different levels of visual field defects. Results: A total of 87 eyes (41 glaucomatous, 46 controls) were analyzed. Glaucoma patients exhibited significantly lower pVD, pFI, PCT, and choroidal vascular indices compared to the controls. MvD was detected in 10 glaucomatous eyes and was associated with a larger β-PPA area, smaller choroidal luminal and stromal areas, and worse mean deviation (MD) values. Multivariate regression showed that the number of ocular hypotensive treatments and StructureIndex variables were significantly associated with PCT (adjusted R2 = 0.14). Logistic regression analysis identified MD, MD slope, and β-PPA area as variables significantly associated with the presence of MvD. ROC analysis showed that the presence of MvD had good discriminatory ability for visual field mean defects (MDs) (AUC = 0.77, 95% CI: 0.69–0.87; p = 0.005). Conclusions: Peripapillary MvD detected by OCTA is associated with reduced choroidal vascularity, increased β-PPA, and greater visual field deterioration in glaucoma patients. MvD may serve as a structural marker associated with functional deterioration in glaucoma patients.

Background: Evidence on long-term visual field progression in childhood glaucoma compared with open-angle glaucoma (OAG) is limited. We compared the rate and timing of visual field progression and identified predictors of final visual field status. Methods: Single-center, retrospective, observational study including childhood glaucoma and OAG, with ≥3 reliable visual field tests and ≥2 years of follow-up. Visual fields were obtained with Octopus perimeter (Haag-Streit Diagnostics, Köniz, Switzerland) with the G grid and TOP strategy. Visual field progression was evaluated using the rate of change in mean defect (MD, dB/year). Rates were compared with the Mann–Whitney U test. Timing was evaluated with Kaplan–Meier and restricted mean survival time (RMST). Cox models assessed risk of progression. Secondary analysis used multiple linear regression to identify predictors of final MD. The mean follow-up duration was 5.7 ± 2.6 years. Results: 171 eyes (87 childhood glaucoma, 84 OAG) were analyzed. Childhood glaucoma had worse baseline MD (10.7 ± 7.5 dB) than OAG (5.1 ± 6.5 dB, p < 0.001), and underwent more surgeries, while OAG used more medications. The median MD progression rate was −2.3 dB/year [IQR: −5.6 to 0.1] in childhood glaucoma vs. 0.0 dB/year [IQR: −1.2 to 1.3] in OAG (p < 0.001), a value consistent with functional stability under treatment, with some eyes showing negative slopes indicating relative improvement. In Octopus perimetry, MD is expressed on a positive scale, so a negative slope reflects absence of visual field worsening, suggesting comparatively greater deterioration in OAG. Kaplan–Meier curves showed similar progression-free survival between groups (Log-Rank p = 0.284). RMST at 12 years was 10.93 years in childhood glaucoma and 10.56 years in OAG (difference ≈ 4.4 months, not clinically relevant). These survival results should be interpreted cautiously due to the low number of progression events and the high censoring rate. In regression, baseline MD was the strongest predictor of final MD; a higher number of medications was associated with worse final MD; number of surgeries and follow-up duration were not significant predictors. Conclusions: MD slopes suggested faster deterioration in OAG than in childhood glaucoma, whereas the timing to first progression was similar between groups. Baseline differences and treatment patterns were consistent with functional stability in childhood glaucoma under current management strategies. These findings support individualized follow-up and timely intervention, especially in pediatric patients.

Introduction: To analyze effects of dynamic corneal response parameters (DCRs) on visual field (VF) progression in normal-tension glaucoma (NTG) and hypertension glaucoma (HTG). Methods: This was a prospective cohort study. This study included 57 subjects with NTG and 54 with HTG, followed up for 4 years. The subjects were divided into progressive and nonprogressive groups according to VF progression. DCRs were evaluated by corneal visualization Scheimpflug technology. General linear models (GLMs) were used to compare DCRs between two groups, adjusting for age, axial length (AL), mean deviation (MD), etc. VF progression risk factors were evaluated by logistic regression and receiver operating characteristic (ROC) curves. Results: For NTG, first applanation deflection area (A1Area) was increased in progressive group and constituted an independent risk factor for VF progression. ROC curve of A1Area combined with other relevant factors (age, AL, MD, etc.) for NTG progression had an area under curve (AUC) of 0.813, similar to the ROC curve with A1area alone (AUC = 0.751, p = 0.232). ROC curve with MD had an AUC of 0.638, lower than A1Area-combined ROC curve ( p = 0.036). There was no significant difference in DCRs between the two groups in HTG. Conclusion: Corneas in progressive NTG group were more deformable than nonprogressive group. A1Area may be an independent risk factor for NTG progression. It suggested that the eyes with more deformable corneas may also be less tolerant to pressure and accelerate VF progression. VF progression in HTG group was not related to DCRs. Its specific mechanism needs further studies.

Background Exercise is widely known to lower intraocular pressure and increase ocular blood flow, which may be beneficial for glaucoma management. However, there are few studies that have reported on the relationship between exercise and glaucoma progression. The aim of our study was to investigate the exercise habits of those with primary open angle glaucoma (POAG) and its association with the progression of visual field (VF) loss. Methods Daily physical activity (PA) was monitored by an accelerometer (ActiGraph wGT3x-BT) which patients wore for more than 10 h of being awake on their right wrists for 1 week. Results Seventy-one non-progressive and 27 progressive patients were enrolled in the study. 24-h moderate to vigorous physical activity (MVPA) exercise showed that POAG patients had similar variation trends consisting of 3 wave peaks and 2 wave hollows. Minutes spent in MVPA was 19.89 ± 15.81 and 21.62 ± 15.10 during 07:00–09:00 h ( p  = 0.204), 15.40 ± 14.49 and 15.67 ± 12.43 during 15:00–17:00 h ( p  = 0.822) and 17.26 ± 21.11 and 11.42 ± 11.58 during 18:00–20:00 h ( p  = 0.001) in the non-progressive and progressive group, respectively. Univariate analysis indicated that 10 min of MVPA (18:00–20:00 h) [odds ratio, OR (95% CI) = 0.82 (0.73, 0.92)], average mean arterial pressure [OR (95% CI) = 0.96 (0.94, 0.98)], age [OR (95% CI) = 1.06 (1.03, 1.08)], male [OR (95% CI) = 0.67 (0.48, 0.96)], spherical equivalent [OR (95% CI) = 1.14 (1.07, 1.22)] and IOP-lowering medications [OR (95% CI) = 1.54 (1.16, 2.05)] were significantly correlated with having progressive VF damage. Multivariable analysis showed that 10 min of MVPA (18:00–20:00 h) [OR (95% CI) = 0.85 (0.75, 0.97)] was associated with progressive VF loss even after adjusting for other risk factors. Conclusions Evening exercise may lower the odds of VF progression, suggesting that exercise habits possibly play an important role in glaucoma progression.

Aim: To compare the results of the water drinking test between glaucomatous eyes with and without visual field progression. Methods: Retrospective analysis of 76 eyes of 76 open angle glaucoma patients followed for a mean period of 26.0 (SD 13.8) months. Patients were submitted to the water drinking test at the beginning of the follow up period. Reliable achromatic automated perimetry tests performed during the studied period were used to characterise visual field progression. All subjects were under clinical therapy and had an intraocular pressure (IOP) lower than 17 mm Hg monitored by isolated measurements during the follow up period. The results of the water drinking test were compared between glaucomatous eyes with and without visual field progression. Results: Twenty eight eyes reached definite visual field progression. There were no significant differences in the mean age, sex, race, basal IOP, number of antiglaucomatous drugs, initial mean deviation (MD), and corrected pattern standard deviation (CPSD) between eyes that showed visual field progression and the ones who did not progress. A significant difference of 1.9 (SD 0.6) mm Hg (p = 0.001, analysis of covariance; 95% CI 0.8 to 3.0) was observed between glaucomatous eyes that showed visual field deterioration and glaucomatous eyes that did not progress. A significant difference of 16.8% (SD 4.6%) in the mean percentage of IOP variation was also observed between the two groups (p<0.001, analysis of covariance; 95% CI 7.7 to 26.0). Conclusions: Mean IOP peak and percentage of IOP variation during water drinking test were significantly higher in patients with visual field progression compared with patients who did not progress.

Purpose: To investigate the clinical significance of vessel density (VD) on visual field (VF) progression regarding the severity of glaucoma. Methods: A total of 130 eyes were recruited in this retrospective and longitudinal study. Superficial and deep VDs in circumpapillary and macular regions were measured via ImageJ. The rate of VF progression was defined as the mean deviation (MD) slope (dB/year). Linear regression was used to verify factors affecting deterioration of VF. The eyes with lower superficial VD were further analyzed. Results: Fifty patients with early glaucoma (EG) (MD > −6 dB) and 52 patients with moderate-to-advanced glaucoma (MAG) (MD ≤ −6 dB) were included. A faster progression rate was found in MAG (p = 0.049). Superficial VD was noticeably related to the VF progression rate in total eyes and in MAG (Both Ps ≤ 0.007, respectively). With patients in the lower half of the superficial VD, the VD was significantly associated with the rate of progression (B, 0.049, p = 0.021). This association was independent of the baseline MD and OCT parameters. Conclusion: Decreased superficial VD might conversely affect the progression of glaucoma even in MAG, which suggests superficial VD could be used as a potential marker to foresee the disease progression even in progressed eyes.

BackgroundThis prospective analysis was designed to examine the rate of RNFL loss using scanning laser polarimetry (GDx enhanced corneal compensation (GDxECC)) in progressing versus non-progressing eyes using various methods to define functional progression.MethodsGlaucoma suspect and glaucomatous eyes with ≥3 years of follow-up participating in the Advanced Imaging for Glaucoma Study were enrolled. All eyes underwent standard automated perimetry (SAP) and GDxECC imaging every 6 months. The annual rate of RNFL loss with GDxECC was calculated using linear regression analysis. Functional progression was determined using the Early Manifest Glaucoma Trial (EMGT) criterion, SAP Visual Field Index (VFI) and Progressor software.ResultsFifty-three eyes (30 glaucoma suspect, 23 glaucoma) of 53 patients (mean age 64.5±10.7 years, range 42–79) were enrolled. Eighteen eyes (40%) demonstrated SAP progression during the follow-up period using the Progressor criterion, 10 eyes (18.9%) using the VFI criterion, and 3 eyes (5.7%) using the EMGT criterion. The annual rate (μm/year) of mean RNFL loss was significantly greater (p<0.05) in progressing versus non-progressing eyes using Progressor (−1.24±0.99 vs −0.18±0.49), EMGT (−1.95±0.99 vs −0.46±0.78) and VFI (−1.11±0.64 vs −0.41±0.85) criteria.ConclusionDespite differences in the criteria used to judge functional progression, progressing eyes have a significantly greater rate of RNFL loss measured using GDxECC as compared with non-progressing eyes.

Purpose To compare the two-year outcomes of non-penetrating deep sclerectomy (NPDS) and Ex-PRESS glaucoma shunt. Methods A retrospective chart review of patients who had undergone NPDS or Ex-PRESS since 2012 was conducted. Patients were excluded if they had undergone eye surgery other than cataract extraction, were diagnosed with ocular pathology other than glaucoma or had less than two-year follow-up. Pre- and postoperative visual acuity, intraocular pressure (IOP), number of hypotensive drugs and visual fields were recorded, as well as intra- and postoperative complications. Results Thirty-nine eyes were included in the NPDS and twenty-three eyes in the Ex-PRESS group. There were no differences in baseline IOP and hypotensive drugs, IOP reduction or postoperative IOP-lowering medications between groups. Two years after surgery, IOP decrease compared to baseline was 23.5% with NPDS and 24.8% with Ex-PRESS. Qualified success (a 20% IOP reduction, with IOP ≤ 18 mmHg with or without medication) rates were similar: 53.8 and 69.6% for NPDS and Ex-PRESS. Visual fields progressed in four eyes of the NPDS (10.2%) and in three eyes (8.7%) of the Ex-PRESS group. As regards complications, early hypotony was more frequent after NPDS (9 eyes, 23.1%) than Ex-PRESS (2 eyes, 8.7%), although the difference was not statistically significant. Conclusions Both NPDS and Ex-PRESS produce an IOP-lowering effect of approximately 25%. Success rates are similar after both procedures, and both seem to lead to a stabilization of visual loss.

To evaluate the effect of routine health examination (RHE) for screening primary open angle glaucoma (POAG) in Eastern China. We enrolled patients with newly diagnosed and untreated POAG admitted to the Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai, China. Patients who were screened on RHE and then diagnosed with POAG were classified into the RHE group. The rest were classified as the non-RHE group. Demographic and ocular characteristics, 24-hour intraocular pressure (IOP), and glaucoma grade classified as the mild, moderate and severe groups according to glaucomatous optic neuropathy evaluated based on the enhanced Glaucoma Staging System were compared between the two groups. In total, 172 patients with POAG (74 cases in the RHE group and 98 cases in the non-RHE group) were enrolled. The average age of patients in the RHE and non-RHE groups was 47.53 ± 1.48 years and 51.47 ± 1.46 years, respectively (P = 0.064), while the average mean deviation (MD) was 5.98 ± 0.66 dB and 9.79 ± 0.80 dB (P = 0.001), respectively. The frequency of mild, moderate and severe grade glaucoma in the RHE group was 47.3%, 36.5%, and 16.2%, respectively, while that in the non-RHE group was 27.6%, 31.6%, and 40.8%, respectively (P = 0.001). The presumed visual field MD progression rate for Chinese patients with untreated POAG was 0.97 dB/year. Additionally, the 24-hour IOP curve in the two groups was similar, with the exception of the IOP at 10:00 PM and 2:00 AM, which was higher in the RHE group than that in the non-RHE group. Our study showed RHE was an important and practical method to screen for POAG in Eastern China. RHE also assisted with an earlier diagnosis of POAG and may assist in preventing visual field loss.