Brimonidine tartrate is a relatively selective 
2-agonist that lowers intraocular pressure by reducing aqueous humor production and by increasing uveoscleral aqueous humor outflow. Ocular side effects associated with brimonidine use include pruritus, as well as follicular conjunctivitis. Recently, 2 reports have described the development of anterior uveitis in 5 patients treated with brimonidine.1-2 Herein we report 4 additional cases of uveitis and concurrent allergic conjunctivitis associated with the use of 0.2% brimonidine tartrate. The 4 cases are summarized in Table 1.
Report of Cases
Case 1. An 82-year-old woman sought care from her general ophthalmologist because of redness, blurred vision, and photophobia in her right eye. The patient had a history of glaucoma and had been treated with 0.2% brimonidine tartrate in the right eye during the previous 16 months. Anterior uveitis was diagnosed in the right eye and resolved after a 5-week course of topical 1% prednisolone acetate. The uveitis recurred after the corticosteroids were discontinued, and it failed to improve after 3 weeks of treatment with topical corticosteroids.
The patient was referred to a uveitis specialist, and examination disclosed conjunctival injection in the right eye with mutton-fat keratic precipitates, +2 anterior chamber cells and flare, posterior synechiae, and Koeppe nodules. The left eye was quiet.
A complete blood cell count, HLA-B27 typing, fluorescent treponemal antibody absorption test, angiotensin-converting enzyme level, and chest x-ray film showed no abnormalities.
The uveitis resolved during 6 weeks of treatment with 1% prednisolone acetate, and the corticosteroids were tapered and discontinued. One month later, the uveitis recurred in the right eye and resolved with corticosteroid drops as well as discontinuation of brimonidine. After 3 months, the patient's ophthalmologist once again prescribed brimonidine, and 2 weeks later, the uveitis recurred in the right eye. Again the uveitis responded to topical corticosteroids and discontinuation of the brimonidine. Thereafter, topical 2% dorzolamide hydrochloride was used in the right eye, and no additional episodes of uveitis occurred in 3 years.
Case 2. An 83-year-old woman sought care because of redness, tearing, and photophobia of both eyes. The patient had a history of pigmentary dispersion glaucoma, cataract surgery in the right eye, and an episode of right-sided herpes zoster ophthalmicus 13 months before this episode. Her ocular medications included brimonidine for 12 months, dorzolamide for 11 months, and 0.5% timolol maleate for 20 months in both eyes.
Examination disclosed erythema and scaling of the periocular skin (Figure 1). Bilateral mutton-fat keratic precipitates with +2 to +3 cells and +1 flare in each anterior chamber were present (Figure 2). Results of serologic testing for syphilis, serum angiotensin-converting enzyme level, and a chest x-ray film were normal.
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Figure 1. Bilateral periorbital inflammation and conjunctivitis in patient 2.
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Figure 2. Multiple mutton-fat keratic precipitates in the right eye (A) and left eye (B) of patient 2.
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Brimonidine was discontinued and the patient started treatment with oral prednisone and famciclovir. Four days later, the uveitis was improved and the famciclovir was discontinued. A prednisone taper was begun, and examination 2 weeks later showed no anterior chamber cells and diminished keratic precipitates bilaterally. After this episode of bilateral anterior uveitis, the patient experienced several flares of uveitis in the right eye presumed to be associated with her history of herpes zoster ophthalmicus, but her left eye remained quiet for 22 months.
Case 3. An 81-year-old woman with chronic open-angle glaucoma was examined because of photophobia and redness in both eyes of 1 week's duration. Her ocular medications were carteolol hydrochloride and brimonidine drops for 12 months in both eyes. Examination showed mild erythema of the lids with an intense palpebral papillary reaction, conjunctival scarring, fornix shortening with symblepharon, bulbar follicles, and granulomatous keratic precipitates in both eyes. No cells were visible in the anterior chambers. Complete blood cell count, serum angiotensin-converting enzyme level, serum lysozyme level, and results of purified protein derivative test, syphilis serologic test, and chest x-ray film were normal.
The brimonidine was stopped and the patient was treated with 1% prednisolone acetate. One week later, her conjunctivitis had resolved, the eyelids were clear, the bulbar follicles had resolved, and the keratic precipitates were reduced. The corticosteroids were tapered and the keratic precipitates resolved completely. She had no recurrences in 18 months.
Case 4. A 77-year-old man with a history of bilateral chronic open-angle glaucoma was referred to the uveitis clinic with a 6-month history of recurrent anterior uveitis and papillary conjunctivitis affecting both eyes. Ocular medications included 0.2% brimonidine tartrate for the past 16 months and 0.5% loteprednol etabonate with 0.1% fluorometholone ointment for the past several weeks in both eyes.
Bilateral papillary conjunctivitis with several mutton-fat keratic precipitates and +1 cell and flare were noted. A chest x-ray film, complete blood cell count, fluorescent treponemal antibody absorption test, and serum angiotensin-converting enzyme level were normal. The loteprednol was discontinued and 1% prednisolone acetate was begun. The uveitis resolved during the next 4 weeks and the corticosteroids were tapered and discontinued after 10 weeks of therapy.
Twelve weeks later, the uveitis and conjunctivitis recurred. Topical corticosteroids were restarted and the brimonidine was discontinued. The conjunctivitis and uveitis resolved during the next 3 weeks. Three months later, 0.005% latanoprost was prescribed, and the uveitis had not recurred in 3 years of monitoring.
Comment
We have described 4 cases of a granulomatous anterior uveitis and concurrent conjunctivitis that appear to be related to the use of 0.2% brimonidine tartrate. All of the patients were 77 years or older and had been using 0.2% brimonidine tartrate for more than 1 year. Uveitis recurred in 1 eye rechallenged with brimonidine. In all cases, the uveitis resolved only on cessation of brimonidine treatment. Although case 2 describes recurrent uveitis in the right eye of a patient after brimonidine had been discontinued, we believe this was related to the history of herpes zoster ophthalmicus. The uveitis that occurred while the patient was using the brimonidine was distinct in its bilateral presentation and its granulomatous character.
Medication-induced uveitis has been reported with a number of drugs, including metipranolol and latanoprost, the bisphosphonates, rifabutin, cidofovir, and fomivirsen. Although such a connection was not reported in early clinical studies, brimonidine has recently been associated with the development of uveitis.1-2 The uveitis described in our report was seen with a concurrent allergic conjunctivitis. This contrasts with previous reports in which the conjunctivitis preceded the development of uveitis.1-2 As suggested by Byles et al,1 up to 15% of the patients in clinical trials developed allergic conjunctivitis and may have discontinued the brimonidine before uveitis developed.1, 3
All of our patients were treated before the release of 0.15% brimonidine tartrate (Alphagan P; Allergan Inc, Irvine, Calif), which uses Purite, a preservative different from the benzalkonium chloride used in the original 0.2% brimonidine tartrate. We are unaware of reports of uveitis associated with this more recent preparation.
Overall, brimonidine is a well-tolerated topical glaucoma medication. However, the 5 cases previously reported and the 4 cases described herein suggest that 0.2% brimonidine tartrate should be considered as possible cause of drug-induced uveitis. Furthermore, clinicians considering continued use of brimonidine in the face of conjunctivitis should monitor these patients closely for signs and symptoms of uveitis.
The authors have no relevant finaicial interest in this aricle.
This study was supported in part by grant 1 K08 EY13977-01 from the National Eye Institute, Bethesda, Md (Dr Zegans).
