Moreover, it is important to emphasize that certain patients (8 of 38 subjects in the glaucoma group) were receiving α-2 adrenergic agonist agents. This class of medication (e.g., brimonidine tartrate) is frequently used to reduce the intraocular pressure in patients with glaucoma by reducing aqueous humor production.
50 Additionally, different studies have reported the action of brimonidine on the pupil diameter.
51,52 Brown et al.
51 reported that the drug could inhibit the release of norepinephrine from the sympathetic terminals by acting on presynaptic α-2 adrenergic receptors. As a result, the contraction of dilator muscle mediated by norepinephrine binding to α-1 receptors is decreased, which in turn inhibits mydriasis.
52 This effect is more evident under scotopic conditions, as norepinephrine is the main mediator of nocturnal pupil dilation when unopposed by the acetylcholine-mediated sphincter muscles. In photopic situations, α-2 adrenergic agonist agents show no substantial effect, as they do not affect the sphincter muscles.
52 Hence, the most important effect of α-2 adrenergic agonist agents is mydriasis inhibition (antimydriasis effect), which we did not evaluate in the present study. Furthermore, all measures (peak and sustained responses) were collected based on the patient baseline (relative measures) to decrease the chances of drug influences. The difference between two measures (the baseline pupil diameter and the smallest pupil diameter) was used to determine the peak response of each patient. Additionally, the sustained response was expressed as the pupil diameter at 6 seconds after the flash offset relative to the baseline, as suggested by previous studies.
28 α-2 adrenergic agonist agents would not influence any of the measures once the relative peak and sustained responses were calculated. Moreover, certain studies have reported the occurrence of tachyphylaxis with continuous use of α-2 adrenergic agonist agents in glaucoma patients.
53 Therefore, the chronic use of α agonists may also decrease the pupillary response to this drug. However, even considering these points, we also performed the analysis for the glaucoma patients separately, and the same correlation was found. In particular, the RNFL thickness was associated with the sustained response to blue flashes with a luminance of 250 cd/m
2 in both the group using and the group not using α-2 adrenergic agonist agents.