Drug-induced Bilateral Secondary Angle-closure Glaucoma

A Literature Synthesis

Rory M. Murphy, MD; Belal Bakir, MD; Colm O'Brien, MD; Janey L. Wiggs, MD, PhD; Louis R. Pasquale, MD


J Glaucoma. 2016;25(2):e99-e105. 

In This Article

Materials and Methods

Search Strategy

We conducted a literature search of the National Library of Medicine's PubMed Database (https://www.ncbi.nlm.nih.gov/pubmed) in April 2014 to capture articles relevant to this review. The search terms "bilateral angle closure" and "drug-induced myopia" resulted in 355 and 27 articles, respectively.

After review of these initial reports, any implicated drugs were manually searched for association with ACG, using the drug name along with the terms "angle closure," "myopia," and "glaucoma" interchangeably, in separate searches, to ensure all potentially relevant articles were captured. These drug entities included: Acetazolamide,[11,12,24–28] Anorexiant mix (consisting of phendimetrazine tartrate, caffeine-ephedrine mixture, L-carnitine, green tea extract, and orthosiphon powder),[29] Aspirin,[13] Basic Detox Nutrient (a dietary supplement containing methyl-sulfonyl-methane and several other ingredients),[30] Bupropion,[31] Cabergoline,[32] Citalopram,[33,34] Chlorthalidone,[14,35] Dipivefrine,[14] Ecstasy,[36] Ecstasy and Marijuana,[37] Escitalopram,[38] Flavoxate,[39] Flucloxacillin,[40] Glycopyrrolate,[41] Hydrochlorothiazide[16,42] (also known as Disothiazide[15]), Hydrochlorothiazide and Triamterene,[17] Indapamide,[18,28] Mefanamic acid,[43] Methazolamide,[25,44,45] Metronidazole,[15] Oseltamivir,[46] Paroxetine,[19–22,47,48] Promethazine,[23] Sulfasalazine,[25] Sulfamethoxazole/Trimethoprim,[15] Topiramate,[28,52–65] Topiramate and Sulfamethoxazole/Trimethoprim,[66] and Venlafaxine.[49–51]

Inclusion/Exclusion Criteria

All drugs that met the inclusion criteria had at least 1 case report of either "bilateral transient myopia" or "bilateral angle-closure glaucoma" with additional case reports of unilateral involvement also initially considered. The decision whether to review unilateral, bilateral, or both forms of 2° ACG was made after reviewing literature on Topiramate-induced 2° ACG, the prototypical drug associated with the entity of interest. Fraunfelder et al[9] in 2004 reviewed 86 suspected cases of Topiramate-induced 2° ACG. Only 3 cases described unilateral involvement, with the other 83 cases described as bilateral.[9] In 2012, Abtahi et al[10] reviewed 49 cases of Topiramate-induced 2° ACG and found bilateral findings in all 49 cases. Because the majority of these cases were bilateral, for the purpose of this review we only considered cases with bilateral involvement. Articles were excluded if they were not written in English. Articles published up until April 2014 were included. It was decided to limit Topiramate articles to those published after the last major review in August 2011[10] to remain focused on analyzing the spectrum of drugs producing bilateral 2° ACG and not the absolute number of case reports.

Scoring Systems

We evaluated these reports using the Naranjo adverse drug reaction probability scale[67] to assess the probability that a drug was associated with the reported adverse ophthalmic reaction or whether the side effect could have another cause. Specifically, it is possible that multiple drugs were introduced simultaneously or that some other medical condition known to produce bilateral 2° ACG could have been responsible for the reported ophthalmic event. The Naranjo scale ranges from -4 to +13 and the drug reaction is considered definite if the score was ≥9, probable if 5 to 8, possible if 1 to 4, and doubtful if ≤0.

We also developed a 2° ACG scoring system (Table 1) to determine the likelihood that the adverse drug reaction produced 2° ACG. We designed the 2° ACG scoring system to distinguish 2° ACG from 1° ACG by including features such as myopic shift, posterior uveal effusion, and regression of the condition after discontinuing the offending agent. The 2° ACG instrument was externally validated by applying it to known cases of Topiramate-induced bilateral 2° ACG.

The bilateral 2° ACG score ranged from 0 to 7 and we considered a bilateral 2° ACG score of ≥4 as likely that the drug reaction caused bilateral 2° ACG, although the 2° ACG scores are provided for all drug entities under consideration (supplemental table, Supplemental Digital Content 1, https://links.lww.com/IJG/A61). We did not pick a higher score cutoff because some reports predate the availability of contemporary sonographic instrumentation.

Two independent reviewers (R.M.M. and B.B.) gave each case report a Naranjo scale score and a 2° ACG score. The scores were averaged and rounded up to the higher integer. If the scores between reviewers were discordant by >1 point on either scale, then the final score was determined by a third reviewer (L.R.P.).

Data Extraction and Analysis

For each case report we extracted data on patient age and sex, drug dose used, duration of drug use, indication for drug use, IOP at presentation, degree of myopic shift, recovery period, and performance of laser peripheral iridotomy. Data from the National Centre for Biotechnology Information were used through PubChem (https://pubchem.ncbi.nlm.nih.gov/) to analyze the chemical structures. Each drug was cross-examined for similarities, differences, and patterns, regarding the elements, bonding sequences, and functional groups.