Pupillary block can also be increased by marked pupillary miosis. Despite this cautionary apprehension about pharmacologic dilation precipitating acute angle closure, in reality it is quite rare in a general population.43

There exists a rich, anecdotal literature of everyday life ‘triggers’ for precipitating attacks of acute PACG; reports commonly identified emotional upset (e.g., bad news, pain, fear, illness, an accident) or dim illumination (e.g., in a restaurant or theater). Emotional upset is thought to dilate the pupil through increased sympathetic tone to the iris dilator muscle, whereas dim illumination dilates the pupil through decreased cholinergic tone to the iris sphincter muscle. But why precisely an attack is precipitated under one such circumstance, but not by the countless dilations and constrictions of the pupil during a lifetime of quotidian activity and emotional reactivity, is never clear. Similarly, the forward movement of the lens, which occurs in a variety of situations such as reading, changes in body position, and miotic therapy, has been implicated as a trigger. Diurnal variations in the anterior chamber depth with parasympathetic fluctuations and pupillary diameter,98 and diurnal variations in aqueous secretion have also been suggested as contributory factors.184

The pharamacological precipitation of acute PACG in predisposed individuals, by a variety of medications applied topically, systemically, or transdermally, is better documented.These medications include tranquilizers, bronchodilators, antidepressants, vasoconstrictors including common nasal decongestants, appetite suppressants,

antiparkinsonian agents, cold preparations, antinausea agents, and antispasmodics (Box 15-2).185–189 These drugs are thought to dilate

the pupil through an anticholinergic effect on the iris sphincter muscle, or a sympathomimetic effect on the iris dilator muscle.

Special attention needs to be drawn to the role of the parasympathomimetic drugs, which constrict the pupil and increase pupillary block. These drugs also contract the ciliary muscle, allowing the zonules to relax and the lens to move forward. Although these changes may not always have clinical relevance, the incontrovertible fact is that angle-closure glaucoma can be precipitated by miotic agents in susceptible eyes with narrow angles. (As discussed below, in considerations for managing the fellow eye after an attack of acute PACG, it is advisable to avoid miotics such as pilocarpine in the ‘prevention’ of PACG.) Because of this risk, it is important to repeat gonioscopy when initiating or changing miotic therapy. The strong miotics (e.g., cholinesterase inhibitors) are more likely to produce angle closure because they cause greater constriction of the pupil and induce vascular congestion of the uveal tract.

The proper treatment for miotic-induced angle closure is discontinuing the drug. If the angle remains exceedingly narrow after discontinuing the parasympathomimetic agent or if the patient requires miotic treatment for IOP control, laser iridotomy can be performed

Provocative tests

One goal that remains as elusive as ever has been the ability to predict which eye at risk will proceed towards disease. As recent epidemiologic assessments have demonstrated, most eyes with ‘occludable angles’ do not progress towards PACG.43 This was an especially compelling concern before laser iridotomies were available, since surgical iridectomies were not without morbidity, particularly in terms of complications and cataract formation.50

Some of the above-mentioned observations on the role of body position and pharmacologic effects have historically generated an array of provocative tests: to elevate IOP in conjunction with occlusion of the angle, so as to indicate which eyes ‘at risk’ merit surgical

Box 15-2  Classes of drugs capable of precipitating angle-closure glaucoma in susceptible eyes

Antipsychotic agents

Phenothiazines: e.g., perphenazine (Trilafon), fluphenazine (Prolixin) Anticonvulsants

e.g., Topiramate (Topomax) Antidepressants

Tricyclic agents: e.g., amitriptylene (Elavil), imipramine (Tofanil) Non-tricyclic agents: e.g., fluoxetine (Prozac), paroxetine (Paxil),   venlafaxine (Effexor)

Monoamine oxidase (MAO) inhibitors

e.g., Phenylzine (Nardil), tranylcypromine (Parnate) Antihistamines

e.g., Ethanolamines: e.g., orphenadrine (Norgesic) Antiparkinsonian agents

e.g., Trihexyphenidryl (Artane) Antispasmolytics

Propantheline (Pro-banthine) Dicyclomine (Bentyl)

Antibiotics

e.g., Sulfa, quinine Sympathomimetic agents

Adrenaline (epinephrine), ephedrine Dipivefrin

Amfetamine, hydroxyamfetamine Tetrahydrozoline

Naphazoline Mydriatic agents

All: cyclopentolate, tropicamide, atropine, homatropine, scopolamine Miotics

e.g., Echothiophate (Phospholine Iodide), pilocarpine 2–6% Botulinum toxin

Cardiac agents

e.g., Disopyramide (Norpace)

Modified from Mandelkorn R: Drug-induced glaucoma. In: Zimmerman TJ, Kooner KS, editors: Clinical pathways in glaucoma, New York, Thieme, 2001:333–350.185

intervention.190,191 Most provocative tests were designed to resemble ‘physiologic’ situations, in the hope that the test would mimic the natural history of the condition. Fortunately, two prospective

studies have been conducted, and neither validates the utility or reliability of such examinations.192,193

A variety of testing strategies have been reported: (1) mydriatic stimulation with a weak, short-acting parasympatholytic agent such as tropicamide 0.5% or a weak sympathomimetic such as hydroxyamfetamine, to mildly dilate the pupil and either raise the

IOP194,195 or demonstrate impaired tonographic outflow;196 (2) dark room testing to induce physiologic miosis;197,198 (3) a prone test

with the head resting on one’s arms on a table, arguably shifting the lens anteriorly without dilation;199,200 and (4) complex pharmacologic

provocations, such as applying a mixture of cycloplegics or mydriatics with pilocarpine.201,202

Unfortunately, each of these ‘provocative’ tests produce enough false positives and false negatives to make them unreliable as predictors of true angle closure or angle-closure glaucoma. Most stud-

ies indicate that 10–30% of eyes with well-documented histories of angle-closure glaucoma have negative provocative tests.195,199,202

Furthermore, approximately 5% of eyes with angle-closure glau-

coma have positive provocative tests after peripheral iridectomy.191,199,202 Finally, even a small percentage of normal eyes and