Targeting outflow facility in glaucoma management

Glaucoma is often characterized by decreased pressure-sensitive aqueous outflow through the trabecular meshwork. This defect in pressure-sensitive aqueous outflow is evident from the low tonographic facility of outflow ("C") measured in many patients. The impairment in outflow facility causes the high intraocular pressure (IOP) and large diurnal IOP fluctuations often found in glaucoma. Because large diurnal IOP fluctuations have been shown to be a risk factor for glaucomatous progression, IOP-lowering therapy should aim to achieve a low, stable IOP. Pressure-sensitive aqueous outflow helps prevent and dampen pressure spikes; thus, drugs that enhance outflow facility, in particular, may stabilize as well as lower IOP. Outflow facility is an attractive target for glaucoma treatment because enhancing outflow facility tends to restore the self-regulating tendency of IOP. Older drugs such as the cholinergic pilocarpine and the catecholamine epinephrine act primarily by improving outflow facility. This action is also important for the recently introduced prostamide, bimatoprost, as well as for the prostaglandin prodrug, latanoprost. Realization of the importance of facility of outflow in lowering and stabilizing IOP will stimulate additional research into the mechanism of action of ocular hypotensive agents and will help optimize the medical treatment of glaucoma. (Surv Ophthalmol 48 [Suppl 1]:S17-S20, 2003. (C) 2003 Elsevier Science Inc. All rights reserved.)