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We wished to determine whether eyes with primary open-angle glaucoma (POAG) and differing severity of optic nerve damage also have differences in severity of trabecular meshwork changes.The trabecular meshwork and optic nerve from 26 eyes (14 donors) with the clinical diagnosis of POAG were studied. Severity of disease ranged from increased intraocular pressure (IOP) without damage to eyes with severe visual field loss. Optic nerve cross-sections were examined with light microscopy, and axonal counts were determined. We studied the trabecular meshwork around the circumference of each eye, examining sections from each quadrant with light and transmission electron microscopy. Morphometric measurements were made of the components of the cribriform region and statistically correlated with the axonal counts by the Pearson correlation coefficient.In eyes with advanced POAG, as determined by visual field loss, measurements of structures in the cribriform region of the trabecular meshwork and axon counts were in the same range as those reported previously in POAG. Axon counts showed a significant negative correlation with the amount of sheath-derived (SD) plaque material in the cribriform region: eyes with lower axon counts had larger amounts of SD plaques. Six eyes from four donors with increased pressure but no clinical signs of optic nerve damage showed no changes in axon counts and no increase in plaque material.Increasing severity of optic nerve damage in POAG is accompanied by an increase in the amount of SD plaque material in the trabecular meshwork.