Outflow Obstruction in Pigmentary and Primary Open Angle Glaucoma

To localize the site of outflow obstruction in glaucoma, we evaluated the trabecular meshwork tissues by morphometric methods. Thirty-three specimens from 27 patients with primary open angle glaucoma (n = 13), pigmentary glaucoma (n = 4), and pigment dispersion syndrome (n = 2), and from nonglaucomatous normal subjects (n = 8) were compared. In these specimens, the extent of aqueous channels and the area occupied by these channels where they terminate in cul-de-sacs were measured. In 32 nonglaucomatous normal specimens (six of the eight mentioned plus an additional 26), we discovered that 94% of the surface area of the cul-de-sacs is lined by trabecular cells. These measurements were used to calculate the resistance to aqueous outflow offered by cul-de-sacs. Three new concepts are advanced in this report: (1) the cul-de-sacs provide a major portion of the normal outflow resistance, (2) the cul-de-sac area is markedly reduced in pigmentary glaucoma and primary open angle glaucoma, accounting for a major portion of the increase in resistance in these conditions, and (3) macrophages are the major cell type responsible for trabecular meshwork clearance of pigment and debris. A common pathophysiologic sequence of events is proposed for the development of glaucoma in pigmentary glaucoma and primary open angle glaucoma.