Eye (2011) 25, 971–980 & 2011 Macmillan Publishers Limited All rights reserved 0950-222X/11 www.nature.com/eye 1,2 1 1 Non-steroidal drug- MR Razeghinejad , MJ Pro and LJ Katz REVIEW induced glaucoma Abstract vision. The majority of drugs listed as contraindicated in glaucoma are concerned with Numerous systemically used drugs are CAG. These medications may incite an attack in involved in drug-induced glaucoma. Most those individuals with narrow iridocorneal reported cases of non-steroidal drug-induced angle.3 At least one-third of acute closed-angle glaucoma are closed-angle glaucoma (CAG). glaucoma (ACAG) cases are related to an Indeed, many routinely used drugs that have over-the-counter or prescription drug.1 Prevalence sympathomimetic or parasympatholytic of narrow angles in whites from the Framingham properties can cause pupillary block CAG in study was 3.8%. Narrow angles are more individuals with narrow iridocorneal angle. The resulting acute glaucoma occurs much common in the Asian population. A study of a more commonly unilaterally and only rarely Vietnamese population estimated a prevalence 4 bilaterally. CAG secondary to sulfa drugs is a of occludable angles at 8.5%. The reported bilateral non-pupillary block type and is due prevalence of elevated IOP months to years to forward movement of iris–lens diaphragm, after controlling ACAG with laser iridotomy 5,6 which occurs in individuals with narrow or ranges from 24 to 72%. Additionally, a open iridocorneal angle. A few agents, significant decrease in retinal nerve fiber layer including antineoplastics, may induce thickness and an increase in the cup/disc ratio open-angle glaucoma. In conclusion, the occurs after ACAG, which mandates lifelong majority of cases with glaucoma secondary to care even when iridotomy has apparently 7–10 non-steroidal medications are of the pupillary alleviated the glaucoma attack. Although block closed-angle type and preventable if the drug-induced ACAG is relatively uncommon, at-risk patients are recognized and treated it is a serious adverse reaction which, if not prophylactically. recognized in a timely manner, may result Eye (2011) 25, 971–980; doi:10.1038/eye.2011.128; in severe morbidity and even permanent published online 3 June 2011 visual loss. Medications have a direct or secondary effect, Keywords: acute closed-angle glaucoma; either to stimulate sympathetic or inhibit 1Glaucoma Service, Wills sympathomimetic drugs; parasymaptholytic parasympathetic activation causing pupillary Eye Institute, Thomas drugs; central nervous system drugs; secondary dilation, which can precipitate ACAG in Jefferson University, Philadelphia, PA, USA closed-angle glaucoma predisposed patients (pupillary block CAG). In eyes predisposed to angle closure by their 2 characteristic biometric features (short axial Department of Ophthalmology, Shiraz length and small anterior chamber), choroidal Introduction University of Medical volume expansion also is considered as a Sciences, Shiraz, Iran Glaucoma is a form of optic neuropathy with contributing factor in inducing angle closure by specific visual field loss. It is usually associated slight forward movement of the lens and then Correspondence: with raised intraocular pressure (IOP) and may narrowing and increasing resistance in the iris– MR Razeghinejad, be divided into primary and secondary forms.1,2 lens channel.11 The other mechanism for CAG is Department of Ophthalmology, Khalili All types of glaucoma are categorized as open thickening and forward movement of lens, Hospital, Shiraz, Iran angle or closed angle based on the status of ciliary body rotation, and choroidal effusion, Tel./Fax: þ 711 647 1479. iridocorneal angle. If the cause of glaucoma can which occur in patients with open or narrow E-mail: razeghinejad@ be identified, then the closed-angle glaucoma iridocorneal angle (non-pupillary block CAG). yahoo.com (CAG) or open-angle glaucoma is secondary. This process seems to be an idiosyncratic Glaucoma can occur as a consequence of reaction to certain systemic medications. Received: 26 January 2011 Accepted in revised form: some medications administered directly to the Most attacks of drug-induced pupillary block 26 April 2011 eye or systemically within the body. Untreated CAG occur in individuals that are unaware that Published online: 3 June drug-induced glaucoma can lead to loss of they have narrow iridocorneal angles. 2011 Non-steroidal drug-induced glaucoma MR Razeghinejad et al 972 Physicians using these drugs cannot practically send each Acetazolamide, an oral carbonic anhydrase inhibitor, and every patient to an ophthalmologist for gonioscopy, can induce non-pupillary block CAG similar to other but they should be informed that patients wearing thick sulfa agents.23 hyperopic glasses are at risk. They can perform the lateral penlight test to estimate anterior chamber depth and send Mydriatics the suspicious patients to an ophthalmologist for gonioscopy.12 The at-risk patients who are going to use the Topical anticholinergic/cycloplegics agents used for CAG inciting drugs should be offered a prophylactic pupillary dilation for fundus examination should be iridotomy to prevent acute attacks. These patients need to used with caution in the susceptible patients. It has been be followed for any possible synechia formation and shown that the iris volume increases after pupil dilation chronic CAG as long as they use the drugs.13 in narrow-angle eyes even in those with open Numerous systemic medications have been implicated iridotomies, which augments the possibility of CAG.24 in the cause of drug-induced glaucoma and the most Pandit and Taylor25 in a systematic review stated that the common medications that induce glaucoma are risk of inducing ACAG following mydriasis with corticosteroids. In our previous review,14 all drugs tropicamide alone is close to zero and no case being causing glaucoma, including steroids, have been identified. The risk with long-acting or combined agents discussed; the present review is more comprehensive was between 1 in 3380 and 1 in 20 000. However, with recent references and discusses the treatments in Mapstone26 reported sever IOP elevation, which detail. This review will discuss the non-steroidal necessitated antihypertensive treatment in 19 out of 58 medications that are involved with glaucoma induction. patients with narrow iridocorneal angle who underwent tropicamide pupil dilation. Topical cycloplegics have been shown to cause significant IOP elevation in 2% of the apparently normal Ocular agents population, increasing to 23% of patients with known primary open-angle glaucoma.27,28 It is recommended Antiglaucoma drugs that the IOP be rechecked after dilation in glaucoma Cholinergic agents, topical anticholinesterase, pilocarpine, patients with significantly damaged optic nerve heads. and intraocular acetylcholine and carbachol are commonly The rise in IOP may be related to decreased aqueous used cholinergic agents in ophthalmic practice. These outflow, resulting from decreased pull on the trabecular agents can, however, induce ACAG due to anterior meshwork due to ciliary muscle paralysis.29 Valle30 movement of the iris–lens diaphragm.3 In addition to reported an increase in aqueous inflow in patients who narrow angle, the eyes with zonular weakness or experienced a rise in IOP following pupillary dilation exfoliation syndrome seem to be particularly prone to and also suggested a decrease in aqueous outflow in the developing miotic-induced CAG.15 Surprisingly, same patients. pilocarpine may also precipitate ACAG by inducing mydriasis. This is due to an impurity of the stereoisomer Ointments of pilocarpine, jaborine, an atropine-like drug that even today, with improved manufacturing, occasionally is Ointments are commonly used after ophthalmic surgery. reported.16 Additionally, these agents can induce Intraocular penetration may cause inflammation and non-pupillary block CAG with inducing aqueous open-angle glaucoma. One of the reported complications misdirection (malignant glaucoma).17 of intraocular ointments is toxic anterior segment shock Sympathomimetics, especially those with a-1agonistic syndrome that may lead to glaucoma due to trabeculitis activity, cause mydriasis and can precipitate ACAG in and fibrin membranes.31 In 1972, Sugar and Airala32 predisposed individuals. Topical phenylephrine and its proposed that ointments should be avoided on the first prodrugs dipivefrin and apraclonidine have been day or so postoperatively. documented to induce ACAG.3,18–20 Latanoprost has been associated with ACAG in two Botulinum toxin cases.21 Sakai et al22 had reported about ciliochoroidal effusion induced by latanoprost in a patient with Sturge– Botulinum neurotoxins act primarily at peripheral Weber syndrome. Enhanced uveoscleral outflow is the cholinergic synapses, including the skeletal muscle mechanism of latanoprost IOP reduction. Yalvac et al21 neuromuscular junction, causing transient muscle paresis speculated that the increased flow through the ciliary by inhibiting the release of acetylcholine. However, muscles caused swelling of the ciliary body and pushed botulinum toxins could cause pupillary dilation when the iris–lens diaphragm anteriorly, initiating an ACAG. injected periocularly. It diffuses toward the ciliary Eye Non-steroidal drug-induced glaucoma MR Razeghinejad et al 973 ganglion and blocks its activity or acts at the pupillary Table 1 List of sulfa drugs sphincter muscle of the iris. Corridan et al33 reported a Antibiotics Rheumatologic drugs case of