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Park and Chun: Comparison of Allergy Prevalence between Brimonidine/Timolol Fixed Combination and 0.15% Brimonidine in Glaucoma Patients
Original Article

J Korean Ophthalmol Soc 2018;59(5):451-458.

Published online: 25 September 2018

DOI: https://doi.org/10.3341/jkos.2018.59.5.451

Comparison of Allergy Prevalence between Brimonidine/Timolol Fixed Combination and 0.15% Brimonidine in Glaucoma Patients

Eun Jung Park, MD, Yeoun Sook Chun, MD, PhD

Department of Ophthalmology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea

Address reprint requests to Yeoun Sook Chun, MD, PhD Department of Ophthalmology, Chung-Ang University Hospital, #102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea Tel: 82-2-6299-1666, Fax: 82-2-6299-3231 E-mail: yschun100@hanmail.net

Received 7 December 2017       Revised 12 January 2018       Accepted 18 April 2018

Copyright © 2018 Korean Ophthalmological Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To compare the allergy prevalence and clinical manifestations of 0.2% brimonidine/0.5% timolol fixed combination (BTFC) and 0.15% brimonidine in Korean patients with glaucoma.

Methods

We retrospectively analyzed the medical records of 196 glaucoma patients treated with BTFC and 234 glaucoma patients treated with 0.15% brimonidine. We compared sex, age, type of glaucoma, treatment period, allergy history, onset time of ocular allergy and clinical characteristics of allergy in the two groups.

Results

Ocular allergy percentages 10.14% in the BTFC group and 22.02% in the 0.15% brimonidine group, and the risk of allergy was approximately 0.4 times lower in patients using BTFC (hazard ratio = 2.5, p = 0.009). The BTFC group developed ocular allergy at a mean of 20.5 months (range: 1.7–51.1 months), and the 0.15% brimonidine group developed ocular allergy at a mean of 7.7 months (range: 0.4–50.8 months). In the BTFC group, 50% of the ocular allergy occurred within 15 months, and within 5 months in the 0.15% brimonidine group. Clinical characteristics of brimonidine allergy involved two types of conjunctival follicles and conjunctival papillae, but there were no significant differences in incidence according to allergy type (p = 0.566).

Conclusions

The prevalence of ocular allergy in the BTFC group was lower than that in the 0.15% brimonidine group in Korean patients with glaucoma. The results of this study are expected to be useful for patient education and compliance improvement using brimonidine.

Keywords: Glaucoma, Korean, Ocular allergy, 0.2% brimonidine/0.5% timolol fixed combination, 0.15% brimonidine

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Figure 1.
Summarized flow chart of patients. Among 430 glaucoma patients who treated with brimonidine 0.2%/timolol 0.5% fixed combination (BTFC) or 0.15% brimonidine, a total 257 patients were enrolled after application of exclusion criteria.
jkos-59-451f1.tif
Figure 2.
Percentage of patients who developed an ocular allergy to 0.2% brimonidine/0.5% timolol fixed combination (BTFC) and 0.15% brimonidine. In the BTFC group, 50% of the ocular allergy occurred within 15 months, and within 5 months in the 0.15% brimonidine group. Compared with 0.15% brimonidine group, only 20% of the ocular allergy occurred in the BTFC group within the first 5 months of treatment.
jkos-59-451f2.tif
Figure 3.
Kaplan– Meier curve, showing distribution of time to withdrawal due to allergic reaction for 0.2% brimoni-dine/0.5% timolol fixed combination (BTFC) versus 0.15% brimonidine. During the entire course of the observation period, the proportion of patients who discontinued treatment due to ocular allergy was lower in the BTFC group than in the 0.15% brimonidine group.
jkos-59-451f3.tif
Figure 4.
Slit-lamp photographs of the ocular allergy on left eye in patient who used 0.2% brimonidine/0.5% timolol fixed combination just in her left eye. (A, B) Right eye showed clear cornea and conjunctive. (C, D) Left eye showed significant hyperemia and distinguishing giant follicles on the upper and lower palpebral conjunctivae.
jkos-59-451f4.tif
Table 1.
Baseline characteristics of patients
  Brimonidine/timolol fixed combination (n = 148) 0.15% brimonidine (n = 109) p-value
Mean age (years) 65.24 ± 14.82 65.58 ± 14.34 0.853*
Sex (male/female) 72/80 52/57 0.256†
Type of glaucoma (n, %)      
 Primary open-angle 10 (6.76) 10 (9.17)  
 Normal tension 114 (77.03) 88 (80.73) 0.246†
 Primary closed-angle 7 (4.73) 6 (5.50)  
 Others 17 (11.49) 5 (4.59)  
Follow up time (months) 20.18 ± 17.13 13.70 ± 14.08 0.614†
Concurrent topical medication (n, %)      
 Prostaglandin analogue 37 (25.00) 17 (15.60) 0.088†
 Carbonic anhydrase inhibitor 14 (9.50) 4 (3.67) 0.086†
 Pirenoxine 7 (4.73) 7 (6.42) 0.587†
 Artificial tear 59 (39.86) 34 (3.19) 0.189†
 Cyclosporine 4 (2.70) 4 (3.67) 0.726†
 Acyclovir ointment – 2 (1.83) 0.179†
Concurrent ocular surface disease (n, %)      
 Dry eye syndrome 60 (40.54) 37 (33.94) 0.300†
 Herpes keratitis – 2 (1.83) 0.179†

Values are presented as mean ± standard deviation (SD) or n (%) unless otherwise indicated.

* p-value by Student's t-test; significance set at < 0.05

† p-value by chi-square test or a Fisher's exact test for two-by-two tables; significance set at <0.05.

Table 2.
Onset of allergy and rate of ocular allergic reaction and systemic adverse event
  Brimonidine/timolol fixed combination (n = 148) 0.15% brimonidine (n = 109) p-value* HR 95% CI
Onset of allergy (months) 20.47 ± 16.71 (1.73–51.07) 7.66 ± 9.91 (0.40–50.83)      
Ocular allergy (n, %) 15 (10.14) 24 (22.02) 0.009 2.50 1.24–5.04
 Blepharoconjunctivitis 2 4      
 Conjunctival follicles 9 15 0.566    
 Conjunctival papillae 6 9      
Systemic adverse event (n) 1 5 0.040 7.07 0.81–61.38

Values are presented as mean ± standard deviation (SD) (range) unless otherwise indicated.

HR = hazard ratio; CI = confidence interval.

* p-value by pairwise comparison of brimonidine/timolol fixed combination vs. 0.15% brimonidine based on the pearson 2 test; significance set at <0.05.

Table 3.
Change of glaucoma medication classes after onset of ocular allergic reaction
  Bfrimonidine/timololl fixed combination (n = 15) 0.15% brimonidine (n = 24)
Betaxol – 6 (25.00)
Timolol – 1 (4.17)
Dorzolamide/timolol 9 (60) 10 (41.67)
Latanoprost 3 (20) 1 (4.17)
Latanoprost/timolol 1 (6.67) –
Tafluprost/timolol 1 (6.67) –
Brinzolamide – 3 (12.50)
Stop medication 1 (6.67) 3 (12.50)

Values are presented as n (%).

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