Ultrastructural characteristics of the trabecular meshwork in primary open-angle glaucoma versus chronic angle-closure glaucoma: a comparative study

BACKGROUND: The trabecular meshwork (TM), the principal site of aqueous humor outflow resistance, plays a pivotal role in the regulation of intraocular pressure (IOP), the key modifiable risk factor for glaucoma. This study aimed to compare the ultrastructural characteristics of the TM in primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG) using transmission electron microscopy (TEM). METHODS: TM specimens were obtained via Kahook Dual Blade goniotomy from 11 POAG and 9 CACG patients and processed for TEM analysis. We evaluated cellular morphology, extracellular matrix (ECM) organization, and collagen fibril architecture (using Feret's diameter). A novel Organelle Severity Index (OSI) was introduced to semi-quantitatively evaluate the cumulative burden of subcellular stress, and clinico-pathological correlations were analyzed. RESULTS: Both POAG and CACG samples exhibited a markedly sparse TM cellularity. Residual cells demonstrated profound subcellular stress, including swollen mitochondria with loss of cristae and accumulation of secondary lysosomes. OSI scores were comparably high in POAG and CACG (1.69 vs. 1.63, P = 0.866), with no significant linear correlations to preoperative macroscopic clinical metrics (all P > 0.05). ECM alterations in both groups included trabecular beam fusion and TM cells abnormally migrating across fractured beams. Quantitatively, collagen fibrils were significantly larger in CACG compared to POAG (60.27 ± 12.97 nm vs. 43.61 ± 8.62 nm, P = 0.018). CONCLUSION: Surgical-stage POAG and CACG share a "final common pathway" of severe TM cellular reduction and structural disruption. However, their distinct collagen fibril architectures suggest divergent ECM remodeling pathways that may contribute to subtype-specific outflow resistance and disease mechanisms.