A physiological approach to glaucoma management: the use of local hormones and the pharmacokinetics of prostaglandin esters.

It appears that a pragmatic approach, based entirely on the ability of a drug or procedure to reduce IOP, has thus far been used to develop modalities for the management of glaucoma. Barring serendipity, it is unlikely that this approach will produce effective new methods for the management of this ocular disorder, which presents an ever-increasing problem in an increasingly longevous and industrialized world population. Although a better understanding of the biology of aqueous humor dynamics and its pathogenesis, combined with new genetic engineering techniques, may eventually lead to the total elimination of glaucoma, that ultimate solution is unlikely to be achieved within the foreseeable future. Thus, a physiologic approach to glaucoma management must be developed, one that takes into consideration all of our recently acquired knowledge of aqueous humor dynamics and all other relevant physiologic principles. A review of currently available information suggests that from a physiologic point of view the best approach to glaucoma management, at least for the next few decades, will be based on the use of receptor-mediated, naturally occurring ocular hypotensive agents, or at least agents that closely resemble such naturally occurring autacoids. Based on the temporal and spatial limitations of the various classes of receptor-mediated autacoids and on differences in the specificity and the nature of the responses they elicit at different sites, we conclude that a physiologic approach to glaucoma management should focus on the use of topically applied local hormones or their analogs. This approach appears to be feasible in light of demonstrations that several members of one family of local hormones, the eicosanoids that are produced within ocular tissues under physiological conditions are effective ocular hypotensive agents. It has been shown that one member of this family, PGF2 alpha, in its esterified form, is an extremely potent ocular hypotensive agent in its esterified prodrug form in both normotensive and glaucomatous human eyes, yielding significant IOP reduction when topically applied in doses less than one-hundredth that of currently available glaucoma medications. Although no intraocular side effects have been noted in human eyes after topical application of PGF2 alpha-1-isopropylester in submaximal ocular hypotensive doses, such side effects as conjunctival hyperemia and foreign body sensation present a problem and a challenge.4