ORIGINAL ARTICLE Carbonic anhydrase inhibitors as fourth drug in primary glaucomas: Is it worth it? Verena Ribeiro Juncal, MD, * Felipe Abdo Jorge, MD, * Augusto Paranhos Jr, MD, PhD, * Tiago Santos Prata, MD, PhD *,† ABSTRACT ● RÉSUMÉ Objective: To evaluate the effectiveness of carbonic anhydrase inhibitors as the fourth drug regarding intraocular pressure (IOP) control in patients with primary glaucomas. Design: Single-centre, prospective study. Participants: Twenty-five eyes from 25 patients with primary glaucomas treated concomitantly with a topical prostaglandin analogue, a β-blocker, an α-adrenergic agonist, and a carbonic anhydrase inhibitor. Methods: Patients followed at the Federal University of São Paulo were enrolled from August to November 2013 and were initially submitted to an ophthalmologic examination where the IOP was measured at 8 AM, 10 AM, and 12 PM. Afterward, patients underwent a 15-day washout of the carbonic anhydrase inhibitor and had their IOP measured again. Results: Most patients were female, white, and with a mean age of 66.4  9.7 years. The removal of the fourth drug had a statistically significant effect on the IOP peak (increase of 1.20 mm Hg, p o 0.01) and mean (increase of 1.23 mm Hg, p o 0.01), but it did not interfere significantly with morning fluctuation of the IOP (p ¼ 0.83). After discontinuation of the fourth drug, the IOP increased Z2 mm Hg in 32% of the patients, and there was a significant increase of the IOP (defined as an IOP change Z20%) in only 5 patients (20%). Age older than 60 years was associated with 20% of the documented IOP change (R 2 ¼ 0.19, p ¼ 0.03). Conclusions: The removal of a fourth medication does not appear to have a clinically significant impact on IOP control in most patients with glaucoma. However, 32% of the patients experienced an IOP increase Z2 mm Hg, with age older than 60 years being the only significant predictive factor. Objet : Évaluer l’efficacité d’inhibiteurs de l’anhydrase carbonique comme quatrième médicament dans le contrôle de la pression intraoculaire (PIO) chez des patients souffrant de glaucome primaire. Nature : Étude prospective unicentrique. Participants : 25 yeux de 25 patients souffrant de glaucome primaire traités concomitamment avec un analogue de prostaglandine topique, un bêta-bloquant, un agoniste alpha-adrénergique et un inhibiteur de l’anhydrase carbonique. Méthodes : Des patients suivis à la Federal University de São Paulo ont été recrutés d’août à novembre 2013 et ont d’abord subi un examen ophtalmologique où la PIO a été mesurée à 8 h, à 10 h et à 12 h. Après 15 jours de lavage avec l’inhibiteur de l’anhydrase carbonique, on a repris les mesures de la PIO. Résultats : La plupart des patients étaient de sexe féminin et de race blanche. L ’âge moyen était de 66,4 ± 9,7 ans. Le retrait du quatrième médicament a eu un effet statistiquement significatif sur la PIO de pointe (accroissement de 1,20 mmHg; p o 0,01) et sur la PIO moyenne (accroissement de 1,23 mmHg; p o 0,01), mais il n’a pas interféré significativement avec la fluctuation en avant-midi de la PIO (p ¼ 0,83). Après l’arrêt du quatrième médicament, la PIO a augmenté de Z2 mmHg chez 32 % des patients, et on a noté une hausse significative de la PIO (définie comme une variation de la PIO de Z20 %) chez 5 patients (20 %) seulement. La variation documentée de la PIO était attribuable à l’âge dans environ 20 % des cas (R 2 ¼ 0,19; p ¼ 0,03). Conclusions : Le retrait d’un quatrième médicament ne semble pas avoir un impact significatif, du point de vue clinique, sur le contrôle de la PIO chez la plupart des patients glaucomateux. Cependant, la PIO a augmenté de >2 mmHg chez 32 % des patients, et l’âge supérieur à 60 ans était le seul facteur prédicteur significatif. Glaucoma is the most important cause of irreversible blindness in the world, and elevated intraocular pressure (IOP) remains the main known risk factor for the development and progression of the disease. 1,2 The main therapeutic goal is to preserve visual function by reducing the IOP, which is the key modifiable risk factor. 3 Medical therapy is the initial approach for most cases of primary glaucoma, due to the fact that the visual outcomes are similar compared with initial surgical treatment and the latter offers more risks to patients. 4 Four categories of topical medications are mainly used for glaucoma treat- ment: prostaglandin analogues, β-blockers, α-adrenergic agonists, and carbonic anhydrase inhibitors. 5 Although response to each medication may vary significantly, carbonic anhydrase inhibitors seem to be the least effective among the 4 classes, as previous studies have shown an average percentage of IOP reduction of 10% to 23%. 6–14 For instance, in the European Glaucoma Prevention Study, the mean IOP reduction in the dorzolamide group was comparable with the placebo group. 14 From the * Glaucoma Service, Department of Ophthalmology, Federal University of São Paulo; and † Hospital Medicina dos Olhos, São Paulo, Brazil The study was presented at the 2014 Arvo meeting, on May 4, at the city of Orlando, FL. Originally received Aug. 13, 2014. Final revision Mar. 13, 2015. Accepted Mar. 22, 2015 Correspondence to Tiago Santos Prata, MD, PhD, Associate Professor of Ophthalmology Glaucoma Service, Department of Ophthalmology, Federal University of São Paulo, Rua Botucatu, 821, Vila Clementino, São Paulo 04023-062, Brazil; tiagoprata@ig.com.br Can J Ophthalmol 2015;50:297–301 0008-4182/15/$-see front matter & 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2015.03.009 CAN J OPHTHALMOL —VOL. 50, NO. 4, AUGUST 2015 297