Section Review Cardiovascular & Renal: Glaucoma: Novel agents and recent therapeutic advances

Abstract

β-Adrenoceptor antagonists have been employed as first-line therapy for reducing elevated intraocular pressure for many years. Recently, and almost simultaneously, three new classes of drugs have been clinically evaluated for treating glaucoma. These are topically-effective carbonic anhydrase (CA) inhibitors, ′₂-adrenoceptor agonists, and prostaglandin F_2′ analogues. Members of each of these groups have been granted approval by regulatory agencies. CA inhibitors and ′₂-adrenoceptor agonists, like β-adrenoceptor antagonists, reduce intraocular pressure by suppressing aqueous humour secretion. Despite the exceptional in vitro potency of dorzolamide in inhibiting human CA II, and physicochemical properties that confer good ocular bioavailability, direct comparison indicates that even this compound is less efficacious than the β-blocker timolol. Since the invention of dorzolamide is widely regarded as a monumental scientific achievement, it does not seem likely that a better CA inhibitor will become available in clinical practice. In contrast, there appears to be scope for improving on the ′₂-adrenoceptor agonist apraclonidine, which has now been approved for glaucoma but with some significant restrictions. Brimonidine may be regarded as a second-generation ′₂-adrenoceptor agonist that has an improved safety profile and well-maintained efficacy. Future knowledge gained with respect to ocular ′₂-adrenoceptor and imidazoline receptor subtype distribution and function could provide yet further improvements.

Prostaglandins are unique in two important respects. They appear to be more efficacious than β-blockers and possess a unique mechanism of action that involves increasing aqueous humour drainage from the eye rather than inhibition of aqueous humour secretion. All indications suggest that prostanoids represent the next real advance in glaucoma therapy.