Abstract:AIM: To investigate the associations of aqueous humor miR-21 and miR-29b levels with the severity of optic nerve damage and GMPE in patients with primary open angle glaucoma(POAG).
METHODS:POAG patients who presented to the hospital from May 2023 to May 2025 were prospectively enrolled as the disease group, and patients with cataract treated during the same period were included as the control group. Baseline characteristics and aqueous humor levels of miR-21 and miR-29b were compared between the two groups. POAG patients were categorized into mild and moderate-to-severe groups according to the mean deviation(MD)of visual field. Clinical characteristics and the expression levels of miR-21 and miR-29b in aqueous humor were compared between the two groups. Correlations and nonlinear associations between miR-21/miR-29b levels and RNFL thickness, visual field MD, and BMO-MRW were evaluated. Furthermore, factors influencing the progression of optic nerve damage were analyzed. Based on prognostic outcomes, patients were divided into good prognosis and poor prognosis groups, and the aqueous humor levels of miR-21 and miR-29b were compared. ROC curve analysis was performed to assess the predictive value of combined GMPE with miR-21 and miR-29b for prognosis in POAG patients.Internal validation and decision curve analysis(DCA)were also conducted.
RESULTS:This study included 151 patients in the disease group(age 56.07±7.59 y, 84 males and 67 females)and 138 patients in the control group(age 56.84±8.25 y, 68 males and 70 females). There were 45 cases in the mild group(age 54.63±7.34 y, 27 males and 18 females)and 106 cases in the moderate-severe group(age 56.68±8.39 y, 57 males and 49 females). There were 118 cases in the good prognosis group(age 55.83±8.07 y, 67 males and 51 females)and 33 cases in the poor prognosis group(age 56.94±8.23 y, 17 males and 16 females). Compared with the control group, the disease group exhibited significantly higher miR-21 levels and lower miR-29b levels(all P<0.001). Compared with the mild group, intraocular pressure and miR-21 levels were significantly higher in the moderate-to-severe group, while RNFL thickness, visual field MD, BMO-MRW, and miR-29b levels were significantly lower(all P<0.01). The miR-21/miR-29b ratio was negatively correlated with RNFL thickness, visual field MD, and BMO-MRW(all P<0.05). Elevated intraocular pressure and miR-21 levels, reduced RNFL thickness, lower visual field MD, and decreased BMO-MRW and miR-29b levels were identified as risk factors for aggravated optic nerve damage in POAG patients(all P<0.05). Compared with the good prognosis group, the poor prognosis group showed significantly higher miR-21 levels and lower miR-29b, RNFL, and BMO-MRW levels(all P<0.001). The combined prediction model incorporating aqueous humor miR-21, miR-29b, RNFL, and BMO-MRW yielded significantly higher AUC and specificity for predicting POAG prognosis than individual parameters alone(both P<0.05). The ROC prediction model demonstrated good consistency, and the combined prediction model exhibited high clinical utility.
CONCLUSION: Aqueous humor levels of miR-21 are significantly elevated while miR-29b levels are significantly decreased in POAG patients, and these alterations are closely correlated with the severity of optic nerve damage and GMPE parameters.
