Effect of brimonidine on pupil diameter

Abstract

We read with interest the articles by Thordsen and coauthors1 and Kesler and coauthors2 regarding the effect of brimonidine tartrate on pupil diameter. Brimonidine is a selective α2 agonist, and stimulation of α2 receptors on presynaptic sympathetic nerve terminals decreases the production, storage, and release of norepinephrine. Unsurprisingly, brimonidine in both 0.2% and 0.15% concentrations will blunt the normal sympathetically mediated pupil dilation that occurs when environmental illumination is reduced. Thordsen and coauthors and Kesler and coauthors propose that brimonidine may palliate low-light vision disturbances after refractive surgery in patients with effective optical zones smaller than their dark-adapted pupils. Thordsen and coauthors further suggest that the response to brimonidine could be incorporated into the preoperative assessment and consent process so individuals with large pupils could be informed that “they may require drops postoperatively to help minimize symptoms.” Tonic reduction of norepinephrine levels in the synaptic junction leads to up-regulation of α1 receptors on the iris dilator muscle. In a study of 10 normal subjects, Brown and coauthors3 showed that once-daily dosing with brimonidine 0.15% initially blocked the pupil dark response, but this effect was blunted within 5 to 11 days (tachyphylaxis); when the medication was discontinued, rebound mydriasis (dark-adapted pupil larger than at baseline) resulted when up-regulated α1 receptors were exposed to normal levels of norepinephrine (Figure 1). Tachyphylaxis was seen in 100% of subjects who showed an initial response. One of us (S.M.B.) performed the same trial on herself using brimonidine 0.2% and experienced tachyphylaxis within 3 days, followed by rebound mydriasis. Rebound mydriasis could be functionally devastating to refractive surgery patients who suffer from disruptive levels of glare disability.Figure 1.: Pupil diameter after dark adaptation at 1 lux for 5 minutes. The right eye was treated with brimonidine 0.15% once daily at noon, and photographs were taken 4 to 6 hours later. Tachyphylaxis began between 5 days and 11 days, and rebound mydriasis occurred when brimonidine was discontinued. This subject's data were collected as part of a previous study.3Since brimonidine cannot be used chronically for the relief of low-light visual symptoms, its usefulness in the preoperative-assessment and informed-consent process for refractive surgery is uncertain. Patients should not be given to understand that brimonidine will reliably and consistently reduce their dark-adapted pupil diameters when needed if such a need might arise on a daily or frequent basis. Sandra M. Brown MD Arshad M. Khanani MD aConcord, North Carolina, USA bLubbock, Texas, USA