Page 27 - 21st Century Perspective - Glaucoma Supplement

nonpigmented epithelium of the ciliary body and drained through the trabecular meshwork and, to a
lesser extent, the uveoscleral tissue. It is also understood that the weak links in aqueous flow are the
outflow pathways. Thus, the primary focus of pharmacologic intervention is enhancing aqueous
outflow.

However, two commonly used and effective drug classes — nonselective beta-adrenergic receptor
blockers and carbonic anhydrase inhibitors — reduce aqueous production as their mode of action.
Alpha-adrenergic receptor agonists have somewhat dual mechanisms of action by both inhibiting
aqueous production and enhancing unconventional (uveoscleral) outflow.

Pilocarpine, a parasympathomimetic agent, now minimally used because of the largely aggravating
ocular adverse effects, nicely enhances conventional (trabecular) outflow by stimulating the
contraction of the longitudinal muscles of the ciliary body, thus enlarging the trabecular pores.

The most efficacious class of IOP-lowering medicines, the prostaglandins, stimulates extracellular
matrix metalloproteinases in the uveoscleral tissues to make them more porous, thus enhancing
aqueous outflow through these unconventional (uveoscleral) tissues.

For historical perspective, the modern era of glaucoma medicines began in 1978, with the advent of
timolol ​(Figure 16)​. Initially, timolol was administered twice daily, but further research found that

once-daily administration shortly after awakening worked as well or nearly as well as twice-daily
administration.

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