Efficacy and safety of topical brimonidine in dermatology: A review article.

Brimonidine is a vasoconstrictive agent used to treat several dermatologic disorders. Here, we review the uses of brimonidine in different aspects of dermatology. We searched keywords including rosacea, erythema, topical brimonidine, dermatology, and skin disease in PubMed, Cochrane, and Google Scholar to collect the related published articles. In a review of 15 articles, we found topical brimonidine improved the facial erythema of rosacea. In addition, it reduced the erythema associated with alcohol flushing syndrome, intense pulsed light therapy, and photodynamic therapy. Furthermore, topical brimonidine was used as a hemostatic agent in dermatosurgery procedures such as Mohs surgery and nail surgery to reduce intra-operative and postoperative bleeding. Some side effects such as erythema, flushing, and burning were reported in a few patients. Based on our findings, brimonidine is a beneficial drug that can be used in various dermatologic disorders with negligible side effects.

Carvedilol ameliorates persistent erythema of erythematotelangiectatic rosacea by regulating the status of anxiety/depression.

The treatment of persistent erythema and rosacea flushing is extremely challenging, especially for patients with anxiety. The aim of this study was to verify the efficacy of carvedilol in rosacea patients with persistent erythema and flushing. A total of 156 patients were randomized to use oral carvedilol 5 mg bid (twice per day) (n = 105) or topical brimonidine (n = 51) for a 10-week period with 6 weeks of follow-up. Both the efficacy of carvedilol and the status of anxiety/depression were analyzed by patient self-assessment (PSA), clinician erythema assessment (CEA), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9). Our study found that carvedilol exerted a dramatic reduction in CEA/PSA scores and sting/burning sensation scores in comparison to topical brimonidine. Additionally, carvedilol treatment dramatically improved telangiectasia, erythema, and pigmentation with no obvious side effects. Patients with carvedilol treatment showed an improvement of depression/anxiety, as reflected by lower GAD-7 and PHQ-9 scores than patients with topical brimonidine. Notably, we found carvedilol treatment had better outcomes among patients under 30 years of age with rosacea younger than 30 years old. Conclusively, our findings reveal that carvedilol could quickly and effectively improve facial erythema, which might stem from the improved the status of anxiety/depression.

The Results of Preoperative Use of Topical Brimonidine in Strabismus Surgery.

Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels (P < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 (P < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.

Difference in vasoconstrictors: oxymetazoline vs. brimonidine.

OBJECTIVE: Topical oxymetazoline and brimonidine are the only medications approved for treating persistent facial erythema of rosacea. This review aims to investigate the efficacy, safety, pharmacodynamics, and pharmacokinetic properties of oxymetazoline and brimonidine. METHODS AND MATERIALS: Phase II and phase III clinical studies evaluating oxymetazoline and brimonidine were assessed to compare their efficacy and safety. RESULTS: In their respective phase III trials, both oxymetazoline and brimonidine met the primary efficacy outcome of having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment (SSA) Scales compared to the vehicle control. Treatment related adverse events of oxymetazoline and brimonidine are most often mild and localized. CONCLUSIONS: Topical oxymetazoline and brimonidine are effective for the management of persistent facial erythema associated with rosacea with a few mild and localized adverse effects. Further long-term research is imperative to further understand their long-term effects.

Drug-induced ocular inflammation.

AIM: Drug-induced ocular inflammation is rare and may be overlooked as a cause of uveitis. The main objective was to describe the causes of drug-induced ocular inflammation. Secondary objectives included uveitis complications and drug rechallenge reactions. METHODS: A retrospective chart review at Auckland District Health Board's tertiary uveitis clinic (Auckland, New Zealand) was performed. Participants were identified using the uveitis database, which consists of 2,750 subjects. Fifty eyes of 35 subjects had drug-induced inflammation. RESULTS: Drug-induced inflammation occurred in 1.3% of subjects with uveitis. Mean age was 66.8±15.6 years, and 25 subjects (71.4%) were female. Drugs responsible were bisphosphonates (24 subjects, 68.6%), brimonidine (one subject, 2.9%), etanercept (three subjects, 8.6%), immune checkpoint inhibitors (two subjects, 5.7%), BRAF inhibitors (three subjects, 8.6%), EGFR inhibitors (one subject, 2.9%) and allopurinol/perindopril (one subject, 2.9%). In subjects with bisphosphonate inflammation, anterior uveitis occurred in 22 (91.7%) and scleritis in two (8.3%). A positive rechallenge reaction occurred in two subjects with zoledronate and one with alendronate. Uveitis occurred in six subjects (17.1%) treated with cancer drugs including immune checkpoint inhibitors, BRAF inhibitors and EGFR protein kinase inhibitors. Subjects with cancer-drug-induced uveitis were managed with corticosteroids and five subjects were able to continue therapy; in one subject uveitis was uncontrollable and required drug cessation. CONCLUSIONS: Ocular inflammation caused by bisphosphonates is usually mild and resolves on medication withdrawal. Uveitis seen in association with newer cancer medications can be more severe, but in most cases it can be managed without medication cessation.

Brimonidine-associated uveitis - a descriptive case series.

BACKGROUND: Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon to avoid mis-diagnosis and over-treatment with topical steroids which in turn may increase intraocular pressure (IOP). This is the largest case series including the longest patient follow-up in the current literature. METHODS: Sixteen patients (26 eyes) with consultant diagnosed brimonidine-associated anterior uveitis in a tertiary referral glaucoma clinic presenting between 2015 and 2019 were included in this retrospective case series. Clinical records were taken for descriptive analysis. Main outcome measures were the key clinical features, and disease course (therapy, IOP control, patient outcome). RESULTS: Key features were conjunctival ciliary injection and mutton fat keratic precipitation in all eyes. The findings were bilateral in 10 patients. Time between initiation of brimonidine treatment and presentation was 1 week to 49 months. Glaucoma sub-types were mostly pseudo-exfoliative and primary open angle glaucoma. Brimonidine treatment was stopped immediately. Additionally, topical corticosteroids were prescribed in 18 eyes and tapered down during the following 4 weeks. Thirteen eyes did not need surgical or laser treatment (median follow-up time 15 months). No patient showed recurrence of inflammation after cessation of brimonidine. CONCLUSIONS: This type of anterior uveitis is an uncommon but important manifestation which should always be considered in glaucoma patients on brimonidine treatment. Although treatable at its root cause, problems may persist, especially with respect to IOP control. The latter may necessitate glaucoma surgery after the resolved episode of the uveitis.

Brimonidine-induced unilateral ocular lichen planus: a case report / Líquen plano ocular unilateral induzido por brimonidina: relato de caso

ABSTRACT This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

RESUMO Este relato é para descrever um caso de líquen plano conjuntival unilateral induzido por brimonidina. Como o exame oftalmológico indicava conjuntivite crônica ou pseudopenfigóide induzido por medicamento, o paciente foi submetido a exames oftalmológicos e sistémicos completos, além de biópsia conjuntival e estudos de imunofluorescência direta. Uma mulher de 71 anos de idade com achados unilaterais do olho esquerdo de conjuntivite crônica foi encaminhada ao nosso departamento de Oftalmologia. A paciente relatou que a conjuntivite crônica começou logo após o início do uso da brimonidina tópica. O exame oftalmológico revelou encurtamento do fórnice inferior e do symblepharon. A biópsia conjuntival revelou linfócitos submucosos e distribuição felpuda de fibrinogênio na imunofluorescência direta; isso era sugestivo de líquen plano ocular. Não foram encontradas outras lesões sistêmicas compatíveis com a apresentação do líquen plano. Uma boa resposta foi observada no tratamento tópico com ciclosporina. Pelo nosso conhecimento, este pode ser o primeiro relato de líquen plano ocular unilateral sem achados sistêmicos. A correlação com o início da brimonidina tópica sugere que este pode ser o primeiro caso de líquen plano ocular induzido por brimonidina confirmado por biópsia.

Brimonidine-induced unilateral ocular lichen planus: a case report.

This report was written to describe a case of unilateral brimonidine-induced conjunctival lichen planus. Because the ophthalmic examination indicated chronic conjunctivitis or drug-induced pseudopemphigoid, the patient underwent thorough ophthalmic and systemic examinations, as well as conjunctival biopsy and direct immunofluorescence studies. A 71-year-old woman with unilateral left eye findings of chronic conjunctivitis was referred to our Ophthalmology Department. The patient reported that chronic conjunctivitis began shortly after she initiated use of topical brimonidine. Ophthalmic examination revealed foreshortening of the inferior fornix and symblepharon. Conjunctival biopsy revealed submucous lymphocytes and shaggy distribution of fibrinogen on direct immunofluorescence; this was suggestive of ocular lichen planus. No other systemic lesions were found that were consistent with the presentation of lichen planus. A good response was observed to topical cyclosporine treatment. To our knowledge, this may be the first report of unilateral ocular lichen planus without systemic findings. The correlation with the initiation of topical brimonidine suggests that this might be the first case of biopsy-confirmed brimonidine-induced ocular lichen planus.

Hypertensive acute granulomatous anterior uveitis as a side effect of topical brimonidine. / Uveítis anterior aguda hipertensiva granulomatosa bilateral como efecto adverso a brimonidina tópica.

CLINICAL CASE: The case concerns an 81-year-old woman on treatment with a topical fixed combination of timolol and brimonidine who was diagnosed in the Emergency Department with acute anterior granulomatous hypertensive uveitis. The patient responded favourably to the withdrawal of the eye drops without showing any subsequent relapse. DISCUSSION: Uveitis due to brimonidine is a rare adverse effect, but it must be known. Once the diagnosis is suspected, the effective treatment is the withdrawal of brimonidine, with or without the addition of topical corticosteroids to control inflammation depending on the severity of the condition. It is a process with an excellent prognosis.

Medical Management of Facial Redness in Rosacea.

Persistent centrofacial erythema is a predominant component of rosacea. The authors review the topical and systemic treatments for rosacea-related erythema and flushing to aid in treatment decision making in clinical practice. Databases were searched for literature pertaining to treatment options for erythema related to rosacea. The paucity of large-scale clinical trials in patients with the erythematotelangiectatic rosacea subtype makes it difficult to draw firm conclusions regarding treatment. Although certain topical and oral treatments appear to have modest benefit in reducing erythema, there is a need for high-quality, well-designed, and rigorously reported studies for the treatments for rosacea.

Treatment of Rosacea With Concomitant Use of Topical Ivermectin 1% Cream and Brimonidine 0.33% Gel: A Randomized, Vehicle-controlled Study.

BACKGROUND: There is currently a lack of data on the simultaneous treatment of different features of rosacea. Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have demonstrated efficacy on inflammatory lesions and persistent erythema, respectively. OBJECTIVE: To evaluate the efficacy, safety, patient satisfaction, and optimal timing of administration of IVM associated with BR (IVM+BR) versus their vehicles in rosacea (investigator global assessment [IGA] ≥3). METHODS: Multicenter, randomized, double-blind study including subjects with rosacea characterized by moderate to severe persistent erythema and inflammatory lesions. The active treatment group included the IVM+BR/12 weeks subgroup (once-daily BR and once-daily IVM for 12 weeks), and the IVM+BR/8 weeks subgroup (once-daily BR vehicle for 4 weeks followed by once-daily BR for the remaining 8 weeks and once-daily IVM for 12 weeks). The vehicle group received once-daily BR vehicle and once-daily IVM vehicle for 12 weeks. RESULTS: The association showed superior efficacy (IGA success [clear/almost clear]) for erythema and inflammatory lesions in the total active group (combined active subgroups) compared to vehicle (55.8% vs. 36.8%, P=0.007) at week 12. The success rate increased from 32.7% to 61.2% at hour 0 and hour 3, respectively, in the IVM+BR/12 weeks subgroup, and from 28.3% to 50% in the IVM+BR/8 weeks subgroup. Reductions in erythema and inflammatory lesion counts confirmed the additive effect of BR to IVM treatment. Subjects reported greater improvement in the active subgroups than in the vehicle group, and similar rates for facial appearance satisfaction after the first 4 weeks of treatment in both active subgroups. All groups showed similar tolerability profiles. CONCLUSION: Concomitant administration of IVM cream with BR gel demonstrated good efficacy and safety, endorsing the comprehensive approach to this complex disease. Early introduction of BR, along with a complete daily skin care regimen may accelerate treatment success without impairing tolerability.

J Drugs Dermatol. 2017;16(9):909-916.

Unilateral floppy eyelid syndrome with ipsilateral intolerance to brimonidine / Síndrome da palpebral flácida unilateral com intolerância a brimonidina ipsilateral

Abstract The authors report a case of unilateral floppy eyelid syndrome with ipsilateral intolerance to brimonidine in a 65-year-old man. The singularity of this case is the combination of two rare illnesses of great phlogistic potentiality in the same eye. The purpose of this article is to report a case of unilateral floppy eyelid syndrome with ipsilateral intolerance to brimonidine, emphasizing a possible relation between them. The result was a unilateral keratopathy that emulated an intraepithelial neoplasia. The key to solving the problem was an unexplained anterior uveitis that raised the suspicion of drug toxicity.The upper eyelid eversion of the affected eye during sleep seemed to be the common denominator of both ailments. The bizarre aspect of the epitheliopathy most likely resulted from the combination of trauma, insufficient lubrication, and drug intolerance.

Resumo Os autores relatam um caso de síndrome da pálpebra flácida unilateral com intolerância ipsilateral à brimonidina em um homem de 65 anos de idade. A singularidade deste caso é a combinação de duas doenças raras de grande potencialidade inflamatória no mesmo olho. O objetivo deste artigo é relatar um caso de síndrome da pálpebra flácida com intolerância ipsilateral à brimonidina, enfatizando uma possível relação entre eles. O resultado foi uma ceratopatia unilateral que simulou uma neoplasia intra-epitelial. A chave para resolver o problema foi uma uveíte anterior inexplicável que levantou a suspeita de toxicidade medicamentosa. A eversão da pálpebra superior do olho afetado durante o sono parece ser o denominador comum de ambas as doenças. O aspecto bizarro da epiteliopatia provavelmente resultou da combinação de trauma, lubrificação insuficiente e intolerância ao medicamento.

Association of Central Nervous System Depression With Topical Brimonidine When Used for Hemostasis: A Serious Adverse Event.

Importance: Minor bleeding is the most common complication of dermatologic surgery. Topical brimonidine, 0.33%, gel has been reported for the use of hemostasis in dermatologic surgery. The safety profile and risk of systemic toxic effects when brimonidine is used topically for hemostasis is unknown. Objective: To determine the risk of systemic toxic effects of topical brimonidine, 0.33%, gel when used for hemostasis. Design, Setting, and Participants: In this case series from a private practice (Hollywood Dermatology), 2 patients presented for dermatologic procedures, complicated by persistent bleeding. Interventions: Patients were treated with 10 g of brimonidine, 0.33%, gel applied under occlusion for hemostasis. Main Outcomes and Measures: Mental status, cardiopulmonary function. Results: Both patients experienced deterioration of mental status, respiratory depression, and somnolence. Results from cardiac testing, laboratory workup, and imaging were negative for cardiac or neurologic etiology. Both patients improved in less than 24 hours. Conclusions and Relevance: Topical brimonidine, 0.33%, gel can result in systemic central nervous system toxic effects when used as a hemostatic agent. At present, it is not possible to define a quantity with which brimonidine can be used safely, nor can a safe wound size be defined. We, therefore, urge against the use of topical brimonidine as a hemostatic agent until its safety is further investigated.