Medical treatment of glaucoma--a reappraisal of the risks.

Abstract

There has been an accumulation of evidence in recent years to demonstrate that surgical treatment is more effective than eyedrops at lowering intraocular pressure and preserving the visual field in primary open angle glaucoma.' 2 The argument against primary surgery for glaucoma has been the risk to the eye of performing an intraocular operation. Respiratory and cardiovascular disease are also common in this age group and both may be affected by eyedrops prescribed for glaucoma. Topical 1 antagonistsThere are two main classes of 1 adrenergic antagonists; non-selective, which affect both 13 receptors, found predominantly in the heart, and 12 receptors, found in the lungs. Timolol, cartelol, and levobunalol are non-selective preparations. Cardioselective 1 antagonists bind to 13 receptors preferentially and have relatively less effect on 12 receptors. Respiratory side effects are less common with cardioselective preparations but they may still occur and they should be avoided in patients with airways obstruction.Side effects of treatment with oral 1 antagonists include heart failure, hypotension, and bronchospasm.The same side effects occur with topical therapy.6 7 Drugs administered topically to the eye gain access to the systemic circulation via the nasolacrimal duct and the nasal mucosa. This avoids first pass metabolism by the liver and significant amounts of topically administered drugs may be absorbed into the systemic circulation. For example, two drops of a 0 5% timolol solution, one to each eye, can approximate to the 10 mg oral dose given to treat systemic hypertension or angina. The first study, recently published in the Lancet, recorded nges in spirometry, an exercise walk tolerance test and measurement of blood pressure, and resting and exercise pulse.'8 Eighty patients, aged over 60 years, without history of airways disease, using timolol for at least 1 year, were recruited into a randomised, double masked, crossover study changing therapy to betaxolol or dipivefrine. The study comprised two phases and all patients who completed both phases underwent a change in therapy. Third party randomisation produced four groups: TTB (timolol-timolol-betaxolol); TTD (timolol-timololdipivefrine); TBT (timolol-betaxolol-timolol); and TDT (timolol-dipivefrine-timolol). During phase I, group TBT was allocated to receive one drop to both eyes of 05°/o betaxolol and group TDT one drop of 0 1% dipivefrine twice daily for four weeks. Groups TTB and l-lTD continued to receive topical timolol for four weeks. In the second phase, groups TBT and TDT returned to timolol while group TTB was allocated to receive one drop to both eyes of 0-/5% betaxolol and group TTD one drop of 0 1% dipivefrine twice daily for 4 weeks. Outcome measures were recorded on enrolment and at the end of each phase.

The medium and long‐term efficacy of primary argon laser trabeculoplasty in avoiding topical medication in open angle glaucoma

“…In recent years the importance of systemic adverse effects provoked by topical medication has been increasingly realised (Everitt & Avorn 1990;Caputo & Katz 1994;Smith & Netland 1994;Diggory & Franks 1996). A diagnosis of glaucoma may in itself produce anxiety and depression, and more than half of medically treated glaucoma patients have reported a decreased quality of life (Spaeth & Birbilis 1991;Bour et al 1993).…”

Survival of glaucoma patients

“…Epstein & Kaufman (1965) pointed out adverse effects of pilocarpine eye drops; Balling et al (1966) and Kerr et al (1982) described cerebral as well as cardial complications after use of epinephrine eye drops. Serious side effects of timolol after local application, are well known for patients with asthma and certain heart diseases (Diggony & Franks 1996). Observations of side effects of acetazolamide are numerous: general malaise, gastrointestinal disturbances, metabolic acidosis, urolithiasis and paresthesia are well known, and bone marrow depression may also occur (Nilsson & Sandholm 1985).…”

“…An increased mortality may possibly indicate an association of glaucoma with systemic diseases or syndromes. Influences on survival of glaucoma patients include a possible impact of the glaucoma itself, as well as adverse treatment effects, for instance eye drops (Epstein & Kaufman 1965, Ballin et al 1966, Kerr et al 1982, Diggony & Franks 1996 and acetazolamide (Nilsson & Sandholm 1985), and association with other diseases which may increase the mortality (Waldmann et al 1996). Belloc (1963), Thorburn & Lindblom (1983), and Bengtsson (1984) have previously commented on survival among glaucoma patients.…”

Bronchoconstriction Secondary to Use of Topical Timolol in a Non-Asthmatic Patient

“…Timolol ophthalmic administration into conjunctiva will drain down the nasopharyngeal mucosa through nasolacrimal duct to the systemic circulation, bypass the liver, where it is normally metabolized [1]. Here, we present a case of timolol-induced bronchospasm in a patient without a history of respiratory disorders and resolved following drug withdrawal.…”

“…It blocks the beta adrenergic receptor in the ciliary body, resulting in the reduction of aqueous humour formation, by decreasing cyclic adenosine monophosphate (cAMP). It possesses the therapeutic advantage of lowering intraocular pressure without changing the pupillary size or causing a diminution of vision and has no significant intrinsic sympathomimetic, direct myocardial depressant or local anesthetic (membrane-stabilizing) activity [1].…”