Corneal Confocal and Specular Microscopic Characteristics in Primary Open-Angle Glaucoma: An Optical Coherence Tomography (OCT)-Based Case-Control Study.

Background: Glaucoma, particularly open-angle glaucoma (OAG), is a leading cause of irreversible blindness, associated with optic nerve damage, retinal ganglion cell death, and visual field defects. Corneal biomechanical properties and cellular components, such as corneal nerve and keratocyte densities assessed by in vivo confocal microscopy (IVCM), may serve as biomarkers for glaucoma progression. This study aimed to explore the relationship between corneal nerve parameters, keratocyte density, and optical coherence tomography (OCT)-derived retinal nerve fiber layer (RNFL) thickness in primary open-angle glaucoma (POAG) patients and controls.

Methods: This case-control study was conducted at Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from January 2023 to October 2024. It included 26 eyes of 17 glaucoma patients and 28 eyes of 18 age-matched controls. POAG was diagnosed based on elevated intraocular pressure (IOP), optic disc changes, RNFL defects, and visual field abnormalities. Participants underwent full ophthalmic evaluation, including OCT for RNFL thickness, specular microscopy, and corneal confocal microscopy (CCM). Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), with Spearman's correlation and linear regression for association analysis.

Results: Anterior stromal keratocyte density was significantly lower in glaucoma patients (436.63±145.44 cells/mm²) compared to controls (546.54±141.20 cells/mm²; p=0.007). No significant difference was found in posterior stromal keratocyte density (p=0.788). Corneal nerve parameters showed a higher nerve fiber length in glaucoma patients (19.25±5.74 mm/mm²), but the difference was not significant (p=0.143). Nerve branch density was significantly higher in glaucoma patients (40.22±23.44 branches/mm²) compared to controls (26.12±10.17 branches/mm²; p=0.054). Specular microscopy revealed significantly lower endothelial cell density in glaucoma patients (2159.8±393.39 cells/mm²) compared to controls (2474.15±272.59 cells/mm²; p=0.002). OCT measurements showed a significantly thinner global RNFL in glaucoma patients (69.79±24.79 µm) compared to controls (98.86±9.04 µm; p<0.001). Spearman's correlation analysis showed that anterior keratocyte density was positively correlated with global (r=0.294; p=0.045), superior (r=0.312; p=0.031), and inferior quadrant RNFL thickness (r=0.285; p=0.049). It was also negatively correlated with central corneal thickness (CCT) (r=-0.367; p=0.039). In multivariate analysis, the duration of glaucoma was significantly associated with RNFL thickness (p=0.011).

Conclusion: This study found that anterior stromal keratocyte density was positively correlated with RNFL thickness, suggesting a potential link between corneal cellular changes and glaucoma severity. Endothelial cell density was significantly lower in glaucoma patients, which may reflect the disease's impact or the effect of medications on corneal health. While corneal nerve parameters did not show significant differences, these findings highlight the importance of corneal biomechanical properties in glaucoma pathophysiology. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings and explore the role of corneal parameters in glaucoma progression.