Brimonidine–timolol fixed combination induced granulomatous inflammation of the eye

Abstract

We report on two cases of granulomatous conjunctivitis and uveitis related with the use of a brimonidine-timolol fixed combination. Case report and a review of medical literature. A 64-year-old man was diagnosed with marked granulomatous uveitis and a 57-year-old woman was diagnosed with granulomatous conjunctivitis. Both patients were using a topical fixed combination of brimonidine 0.2 %-timolol 0.5 % for open angle glaucoma. Bilateral granulomatous uveitis and conjunctivitis were diagnosed after 16 months of treatment with a fixed combination of brimonidine-timolol in both cases. Granulomatous inflammation resolved with the cessation of antiglaucomatous drugs and topical corticosteroid treatment. When the inflammation had resolved completely, both patients were rechallenged with topical brimonidine in one eye only to determine causality. Conjunctival hyperemia is a common side effect of glaucoma medications and is sometimes overlooked. Hyperemia may be associated with other signs such as iritis and keratic precipitates or conjunctival inflammation. In such cases, granulomatous inflammation may be considered in the differential diagnosis. The fixed-combination of brimonidine-timolol may cause this clinical picture.

Brimonidine Induced Anterior Uveitis

“…[2][3][4][5][6] In addition to conjunctivitis, sporadic case reports have emerged since 2000, of anterior uveitis in patients treated with topical brimonidine tartrate. [7][8][9][10][11][12][13][14][15][16][17] In this paper, we report 19 eyes affected by brimonidine induced uveitis, the largest series reported so far. We present the clinical characteristics of this under-diagnosed and easily treatable condition.…”

Brimonidine-associated uveitis – a descriptive case series

“…Clinical signs may differ and there is no pathognomonic appearance as one finds, for example, in Fuch's uveitis syndrome. The previously described clinical spectrum of brimonidine-associated uveitis ranges from simple conjunctival congestion [13], severe follicular conjunctivitis, blepharitis [11,14,15], and punctate corneal epithelial erosions [5], to the full extent of anterior uveitis with corneal endothelial deposition (mutton fat KPs) [4,6], significant anterior chamber activity (cells and flare) [3,4,9] and posterior synechiae (PS) [1,2,7]. PS were present in only three of our patients, while Beltz et al did not find any in their series, despite reporting cells and flare in most cases [4].…”

“…Keratic precipitation and eventually cells or flare in association with these drops, in the absence of systemic inflammatory or infectious disease, were considered as suspicious, even more so in combination with elevated IOP. The selected cases did not undergo a conjunctival biopsy prior to diagnosis as this is not pathognomonic [5]. Serologic and radiological workup was performed in cases where it was deemed indicated (for example bilateral involvements), and included routine laboratory testing, c-reactive protein, differential blood count, antinuclear antibodies, angiotension converting enzyme, soluble IL-2 receptor, HLA B 27, infectious laboratory (tuberculosis, syphilis, borrelia), and chest xray.…”

“…The granulomatous anterior uveitis associated with its use was first described by Byles in 2000 [2]. A cumulative total of 39 cases (68 eyes) within 15 reports [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] have been published since then, the greatest number previously reported being 12 cases (19 eyes) in 2015 [4]. To the best of our knowledge, this is the largest case series of brimonidine associated uveitis, including the longest patient follow-up in the literature.…”

Selective α2-agonists in the treatment of glaucoma: pharmacology, efficacy and safety

“…В литературе описано несколько клинических случаев развития переднего гранулематозного увеита и папиллярного конъюнктивита на фоне лечения Бримонидином [46,47]. Данное осложнение может возникнуть даже спустя год после начала лечения Бримонидином или его фиксированной комбинацией с тимололом [48]. Процесс благополучно разрешается в сроки от 4 дней до 8 нед после отмены препарата [47].…”