Association between Serum Total Bilirubin Level and Patients with Primary Open-Angle Glaucoma in China: A Cross-Sectional, Case-Control Study.

Objective: To investigate the relationship between peripheral blood total bilirubin (TBIL) levels and the risk of primary open-angle glaucoma (POAG). Methods: This study was a cross-sectional, case-control study design. Between April 2021 and January 2022, 198 POAG patients and 205 healthy subjects were recruited from the EENT Hospital of Fudan University. Their clinical information (intraocular pressure, central corneal thickness, vertical cup-disk ratios (VCDR), and axial length) and demographic data were collected. Serum levels of TBIL were measured in enzymes using a Roche C702 biochemical analyzer. The POAG subgroups were classified by gender and VCDR: mild (VCDR ≤ 0.64), moderate (VCDR ≤ 0.85), and severe (VCDR > 0.85). Univariate and multivariate logistic regression analyses were performed. Results: The level of TBIL (11.58 ± 5.16 µmol/L) in the POAG group was higher than that in the control group (10.18 ± 3.38 µmol/L; p < 0.05). In the male subgroup, TBIL was also significantly higher than in the normal control group; TBIL levels were lower in the mild subgroup (10.82 ± 4.48 µmol/L), followed by the moderate subgroup (12.00 ± 5.55 µmol/L) and the severe subgroup (14.47 ± 5.45 µmol/L). The results of the multivariate logistic regression analysis showed that high TBIL levels were a risk factor for male POAG, at 1.126 (95% CI 1.009-1.256). Pearson's analysis revealed that TBIL was positively correlated with intraocular pressure (r = 0.134, p = 0.012), VCDR (r = 0.142, p = 0.046), anterior chamber depth (r = 0.190, p = 0.014), and axial length (r = 0.179, p = 0.019) in the patients. However, no statistical difference (p < 0.05) was observed in the female patients with POAG. Conclusion: The results showed that high levels of TBIL may be related to the pathogenesis of POAG and that the severity of the disease is positively correlated, especially in male patients.

Association between Red Blood Cell Distribution Width and Diabetic Retinopathy: A 5-Year Retrospective Case-Control Study.

PURPOSE: Red blood cell distribution width (RDW) has been regarded as an emerging biomarker of the general population and cardiovascular disease. In this study, we aimed to evaluate the association between RDW and diabetic retinopathy (DR). METHODS: This case-control study included 167 patients with DR, 131 patients with diabetes mellitus (DM), and 170 age- and sex-matched healthy controls from April 2014 to May 2019. Demographic data, laboratory parameters, and ocular examinations were collected. RESULTS: RDW values of the DR group were significantly higher than those of the healthy control (p < 0.001) and DM group (p=0.002). A similar trend was observed when RDW was compared among the 3 groups with respect to age and gender. Logistic regression analysis has shown the OR of RDW was 3.791 (2.33-6.168; p < 0.001) against the control group and was 1.348 (0.997-1.823; p=0.047) against the DM group. CONCLUSION: RDW values were significantly elevated in DR patients, and an elevated RDW was associated with an increased incidence of DR in patients with DM.

Relationship between Oxidative Stress Biomarkers and Visual Field Progression in Patients with Primary Angle Closure Glaucoma.

PURPOSE: To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG). METHODS: A case-control and a prospective cohort study. A total of 94 patients with PACG and 89 normal controls were enrolled. Furthermore, 94 PACG subjects were followed up for at least two years (once every six months). All participants were evaluated for serum levels of superoxide dismutase (SOD), total antioxidant status (TAS), hydrogen peroxide (H2O2), malondialdehyde (MDA), glutathione peroxidase, glutathione reductase, and detailed eye and systematic examination. Binary logistic regression analysis and Cox regression analysis were performed. RESULTS: The serum levels of SOD and TAS in the PACG group were significantly lower than those in the control group (p < 0.001). Meanwhile, PACG subjects had significantly higher levels of MDA and H2O2 than the normal control subjects (p < 0.001). Serum levels of TAS (OR = 0.773, 95%CI = 0.349 - 0.714, p < 0.001), SOD (OR = 0.975, 95%CI = 0.955 - 0.995, p < 0.001), MDA (OR = 1.155, 95%CI = 1.080 - 1.235, p < 0.001), and H2O2 (OR = 1.216, 95%CI = 1.142 - 1.295, p < 0.001) were independent risk/protective factors for PACG. TAS levels (HR = 0.041, 95%CI = 0.008-0.218, p < 0.001), SOD levels (HR = 0.983, 95%CI = 0.971-0.994, p = 0.003), and MDA levels (HR = 1.010, 95%CI = 1.001-1.018, p = 0.015) at baseline were associated with visual field progression. Kaplan-Meier curves reveal that patients with TAS < 0.95/SOD < 143/MDA > 12 had a significantly higher percentage of PACG progression (p < 0.05). CONCLUSIONS: Decreased levels of TAS and SOD as well as increased levels of MDA at baseline were associated with VF progression in patients with PACG. These findings suggest that oxidative stress was involved in the onset and development of PACG.

Relationship between ocular biometry and severity of primary angle-closure glaucoma: relevance for predictive, preventive, and personalized medicine.

BACKGROUND: Several ocular factors have been identified for primary angle-closure glaucoma (PACG), such as a small cornea, elevated intraocular pressure (IOP), shallow anterior chamber, and short axial length (AL). However, the relationship between the severity of PACG and various ocular parameters [IOP, anterior chamber depth, AL, central corneal thickness] is not fully understood. METHODS: A 7-year cross-sectional study. A total of 2254 eyes of 1312 PACG patients (females = 856 [1479 eyes] and males = 456 [775 eyes]) were included. A detailed eye examination was performed. The participants were categorized into gender subgroups followed by subdivision into three different severity groups according to their mean deviation (MD) of the visual fields results as follows: mild (MD ≤ 6 dB), moderate (MD 6-12 dB), and severe (MD > 12 dB) PACG. The associations of ocular biometry with severity of PACG were analyzed using paired Student's t test, multivariate linear regression, and logistic regression analysis. RESULTS: There was a significant positive correlation between the MD and AL in the female subgroup (B = 0.663, p = 0.001, 95%CI = 1.070 to 1.255) but not in the male subgroup. Increased AL levels (mild [OR = 1], moderate [OR = 1.047, p = 0.062, 95%CI = 0.947 to 2.462], and severe [OR = 1.274, p < 0.001, 95%CI = 1.114 to 1.457]) were only associated with the severity of PACG in females. Paired Student's t tests showed that the long AL female eyes have a higher MD value than in the short AL female eyes (mean difference = 3.09, t = 6.846, p < 0.001) in the same subjects, but not in the male subgroup (p = 0.648). CONCLUSIONS: The AL was positively and significantly related to the severity of PACG in female but not male subjects. This finding refers to the PACG pathogenesis and suggests the use of AL assessment in glaucoma monitoring, diagnosis, and progression. This may contribute to further development of personalized strategies in preventive medicine.

COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.

PURPOSE: PLEKHA7 and COL11A1 were genotyped for single-nucleotide polymorphisms (SNPs) to investigate the possible association of these two genes with primary angle-closure glaucoma (PACG) and disease severity. METHOD: A total of 51 PACG cases and 51 normal controls were recruited. Twelve SNPs in the PLEKHA7 (rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) and COL11A1 (rs1676484, rs3753841, rs12138977, rs2126642, and rs2622848) genes were genotyped by direct Sanger sequencing. Distributions of allele frequencies and genotype frequencies in cases and controls, as well as in mild, moderate, and severe subgroups, were compared based on mean defect (MD ≤ 6.00 dB, 6 dB < MD ≤ 12 dB, and MD > 12 dB were considered mild, moderate, and severe, respectively). Independent Student's t-tests and chi-square tests were used to compare characteristics of PACG cases and controls. Chi-square tests were used to compare the distribution of allele frequencies in cases and controls and in MD-based subgroups with various degrees of glaucoma severity. Binary logistic regression was used to compare the distribution of genotype frequencies and calculate odds ratios (OR) with confidence intervals (CI). RESULT: Three of the 12 SNPs in COL11A1, rs1676486 (P=0.026, OR = 2.089, 95% CI = 1.092-3.996), rs3753841 (P=0.036, OR = 1.886, 95% CI = 1.038-3.426), and rs12138977 (P=0.024, OR = 2.133, 95% CI = 1.104-4.123) were found to have a significant association with PACG. Furthermore, in the subgroup analysis, rs1676486 (P=0.018, OR = 2.416, 95% CI = 1.284-4.544; P=0.011, OR = 2.119, 95% CI = 1.204-3.729), rs12138977 (P=0.009, OR = 2.158, 95% CI = 1.287-3.618; P=0.006, OR = 1.962, 95% CI = 1.239-3.106), and rs3753841 (P=0.007, OR = 2.550, 95% CI = 1.344-4.839) showed statistically significant differences between moderate/severe groups and controls. CONCLUSION: Our data suggested that COL11A1 rs1676484, rs3753841, and rs12138977 polymorphisms may be of value for further study as potential gene-dependent risk factors for developing PACG. Moreover, COL11A1 rs1676484 and rs12138977 polymorphisms might be associated with PACG disease severity.