About the pathways to deliver brimonidine to the Muller’s muscle

Abstract

To the Editor: We read with great interest the case report by Alotaibi et al1Alotaibi G.F. Alsukait S.F. Alsalman H.H. Turkmani M.G. Eyelid ptosis following botulinum toxin injection treated with brimonidine 0.33% topical gel.JAAD Case Rep. 2022; 22: 96-98https://doi.org/10.1016/j.jdcr.2022.01.019Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar describing the evaluation of the topical application of brimonidine gel on the upper portion of the eyelid of a patient presenting postbotulinum toxin blepharoptosis. The investigators reported improvement in right eyelid elevation via palpebral fissure measurement 1 hour after application, which persisted for up to 2 hours.1Alotaibi G.F. Alsukait S.F. Alsalman H.H. Turkmani M.G. Eyelid ptosis following botulinum toxin injection treated with brimonidine 0.33% topical gel.JAAD Case Rep. 2022; 22: 96-98https://doi.org/10.1016/j.jdcr.2022.01.019Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar We write this letter to challenge the interpretations to guide future reports on the subject. Although alpha-2 adrenergic agonist ophthalmic eye drops, such as apraclonidine or brimonidine, have been adopted by many clinicians to treat blepharoptosis, more studies are needed to evaluate their efficacy.2Mendonça T.B. Lummertz A.P. Bocaccio F.J. Procianoy F. Effect of low-concentration, non-mydriatic selective alpha-adrenergic agonist eye drops on upper eyelid position.Dermatol Surg. 2017; 43: 270-274https://doi.org/10.1097/DSS.0000000000000967Crossref PubMed Scopus (8) Google Scholar In a nonrandomized clinical trial measuring margin-reflex distance in healthy subjects after the administration of ophthalmic solutions of brimonidine tartrate 0.2%, phenylephrine hydrochloride 0.12%, or naphazoline nitrate 0.05%, the investigators found that brimonidine and phenylephrine had no effect on the eyelid aperture.2Mendonça T.B. Lummertz A.P. Bocaccio F.J. Procianoy F. Effect of low-concentration, non-mydriatic selective alpha-adrenergic agonist eye drops on upper eyelid position.Dermatol Surg. 2017; 43: 270-274https://doi.org/10.1097/DSS.0000000000000967Crossref PubMed Scopus (8) Google Scholar Brimonidine tartrate 0.5% gel (0.33% brimonidine base) has received approval from the United States Food and Drug Administration for use in the topical treatment of erythema of rosacea in adults.3Del Rosso J.Q. Management of facial erythema of rosacea: what is the role of topical alpha-adrenergic receptor agonist therapy?.J Am Acad Dermatol. 2013; 69: S44-S56https://doi.org/10.1016/j.jaad.2013.06.009Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Despite the high concentration, brimonidine is unlikely to permeate through epidermis, dermis, orbicularis oculi muscle, 2 fat pads separated by the orbital septum, and the levator aponeurosis to finally reach and contract the Muller’s muscle (Fig 1). Additionally, the photographic documentation shown reveals the following: (1) a null margin-reflex distance before application, instead of 2 mm (no reflex is seen over the pupil, only on the lid margin); (2) One-hour after application, a contralateral upper eyelid elevation was noted, which is suggestive of voluntary contraction of the levator palpebrae superioris muscles. When considering that the systemic absorption could explain the results, it would be unlikely that the drug would achieve systemic levels to cause contralateral contraction of the Muller’s muscle without any other systemic side effects.4Benkali K. Leoni M. Rony F. et al.Comparative pharmacokinetics and bioavailability of brimonidine following ocular and dermal administration of brimonidine tartrate ophthalmic solution and gel in patients with moderate-to-severe facial erythema associated with rosacea.Br J Dermatol. 2014; 171: 162-169https://doi.org/10.1111/bjd.12881Crossref PubMed Scopus (16) Google Scholar Moreover, accidental conjunctival application would likely only affect the treated eye. Although eye drops instillation can be cumbersome for some patients, there is evidence for the use of naphazoline nitrate 0.05%2Mendonça T.B. Lummertz A.P. Bocaccio F.J. Procianoy F. Effect of low-concentration, non-mydriatic selective alpha-adrenergic agonist eye drops on upper eyelid position.Dermatol Surg. 2017; 43: 270-274https://doi.org/10.1097/DSS.0000000000000967Crossref PubMed Scopus (8) Google Scholar to elevate the upper eyelid, and the recently United States Food and Drug Administration-approved oxymetazoline hydrochloride ophthalmic solution 0.1% for the treatment of acquired blepharoptosis in adults.5Sloan B. This month in JAAD Case Reports: July 2022: eyelid ptosis treated with brimonidine gel.J Am Acad Dermatol. 2022; 87: 44https://doi.org/10.1016/j.jaad.2022.04.038Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Since 2018, one of the investigators (CGW), has adopted over-the-counter ophthalmic solutions containing naphazoline, such as naphazoline hydrochloride 0.03% (Clear Eyes, MedTech Products Inc.) with anecdotal success. Continued research is needed to explore different active ingredients and concentrations in ophthalmic solutions, and also in topical products that could benefit patients who are averse to eye drops. None disclosed.