Prostaglandins: a new approach to glaucoma management with a new, intriguing side effect

This introductory overview considers the advantages of a class of local hormones-the prostaglandins (PGs)-for the management of intraocular pressure (IOP) in glaucoma, over agonists and antagonists of neurotransmitters that dominated this field in the 20th century. PGs and PG analogues, in particular esterified prodrug forms of PGF2 alpha, are effective ocular hypotensive agents, but cause some conjunctival hyperemia and corneal sensory irritation at higher concentrations. Based on structure-activity studies, a 17-phenyl PGF2 alpha prodrug, latanoprost (PhXA41), was found to have a greatly improved therapeutic index, without compromising the ocular hypotensive potency of PGF2 alpha prodrugs. The IOP lowering mechanism of such PGF2 alpha s, increased uveoscleral outflow, can be expected to have great physiologic advantages, especially with respect to normal tension glaucoma, over most currently used ocular hypotensive drugs. The introduction of this new approach has already led to a new insight into the control and clinical significance of this outflow route. Similarly, the newly discovered ocular side effect, PG-induced increase in iridial pigmentation, can be expected to provide insight into the oculo-protective role of iridial melanocytes and into the punative association between a decline in the ocular melanin system and the vulnerability of the eye to some age-related diseases.