Should beta blockers be abandoned as initial monotherapy in chronic open angle glaucoma? The controversy.

βBlockers lower intraocular pressure (IOP) by reducing the rate of aqueous inflow. Shortly after the commercial release of topical timolol maleate in 1978 it became the most widely used ocular hypotensive agent. Its potency, combined with its twice daily frequency of instillation and lack of induction of miosis or accommodative spasm, was seen as a major advantage. Timolol was considered a revolutionary advance in the medical management of glaucoma. In Australia, only laevobunolol later provided an alternative to timolol as a non-selective β blocker, and in 1995 betaxolol hydrochloride offered the choice of a relatively selective β1 blocker. Betaxolol has been demonstrated to have a wider safety margin than the non-selective agents, particularly for the cardiovascular and respiratory systems. It is less likely than timolol to provoke bradyarrhythmias, heart block, and bronchoconstriction. It is also somewhat less effective as an ocular hypotensive agent. In the laboratory, betaxolol has been found to have calcium channel blocking effects independent of its β blocking properties, and this has led to speculation that it may be useful not only in IOP reduction, but also as an inhibitor of episodic vasoconstriction in the optic nerve head region (one of the postulated mechanisms of glaucomatous damage), and as an agent that may offer a modicum of neuroprotection by inhibiting the calcium influx that is an inherent part of apoptosis. To date, optic nerve head concentrations of topically applied betaxolol necessary to produce these additional benefits have not been demonstrated, and there has been no clear, adequately controlled, and robust clinical evidence to support these speculations. Particularly in Europe, other β blockers, such as carteolol, have been available. Possible advantages for some of these molecules include differences in membrane stabilisation properties and partial agonist activity. In Germany, for example, up to 22 different β blockers have been marketed. Despite many claims over the years, no clearcut advantages have been demonstrated for any one molecule, and timolol has retained its clear market lead over all others internationally. Because of its relative selectivity, only betaxolol has been a significant challenger. Before 1978, our antiglaucoma medical options included, cholinergics such as pilocarpine and carbachol, adrenergic agonists such as dipivefrin, and oral carbonic anhydrase inhibitors. Significant problems attended the use of all the non-β blocker options. By eliminating the topical side effects (miosis, dimmed vision, accommodative spasm, and brow ache) and by reducing the required frequency of instillation of the miotics (four times to once or twice daily), by being far Series editors: Susan Lightman & Peter McCluskey