Dilute pilocarpine test for diagnosis of Adie's tonic pupil

Abstract

We have compared the diagnostic ability of different concentrations of 0.125% and 0.0625% dilute pilocarpine for detecting denervation supersensitivity in unilateral Adie's tonic pupil. This retrospective, observational, case-control study involved 117 subjects, consisting of 56 patients with unilateral Adie's tonic pupil and 61 controls with other causes of unilateral dilated pupils. Subjects underwent the dilute pilocarpine test with one of the two concentrations, 0.125% or 0.0625%. Pupillary light reflex was recorded with a dynamic pupillometer at baseline and at 30-40 min after instilling one of the two concentrations of dilute pilocarpine. Diagnostic accuracy of two different concentrations of the dilute pilocarpine test, 0.125% group versus 0.0625% group, were compared by area under the receiver operating characteristic curve (AUC). Diagnostic ability of the dilute pilocarpine test for detecting denervation supersensitivity in unilateral Adie's tonic pupil was significantly better in the 0.0625% group than in the 0.125% group (AUC = 0.954 vs. 0.840, respectively, P = 0.047). In the 0.0625% group, the change in maximal pupil diameter of ≥ 0.5 mm after topical pilocarpine instillation showed 100% sensitivity and 82.8% specificity for detecting Adie's tonic pupil. This study confirmed that pupillary constriction with 0.0625% pilocarpine is better than 0.125% pilocarpine for detecting denervation supersensitivity in Adie's tonic pupil. Digital pupillometry is a reliable method for assessing denervation supersensitivity in Adie's tonic pupil.

Figure 1

(A) Scatter plots of the amount of anisocoria after dilute pilocarpine instillation in patients with unilateral tonic pupil with respect to anisocoria at baseline in both pilocarpine dosage groups. There were no significant differences of ansiocoria in darkness both at baseline (P = 0.157) and after pilocarpine instillation (P = 0.901) between the two groups. (B) Dot plots of the change in anisocoria from baseline to post-pilocarpine test for each patient and control in both pilocarpine dosage groups. The change in anisocoria from baseline to post-pilocarpine test in the patients with unilateral tonic pupil were 1.30 ± 0.92 mm in the 0.125% group and 0.90 ± 0.64 mm in the 0.0625% group showing no significant difference between the two pilocarpine dosage groups (P = 0.08). In both pilocarpine dosage groups, comparison of patients with the respective controls revealed significant differences in the amount of change in anisocoria (both P < 0.01). The red error bars show 25% and 75% percentiles of the change in anisocoria from baseline to post-pilocarpine test for each patient and control in both pilocarpine dosage groups.

Figure 2

Representative cases of dilute pilocarpine test in unilateral Adie's tonic pupil. The pupillary light reflex (PLR) was recorded with a digital pupillometer. Pupil photographs were taken at baseline (a-1 and b-1) and 30–40 min after pharmacological testing (a-2 and b-2). Both patients at baseline showed mydriasis in the right eye (a-1 and b-1). Eight pupillary light reflex parameters were presented with pupil response curves at baseline (a-3 and b-3) and after 0.125% pilocarpine (a-4) and 0.0625% pilocarpine (b-4) instillation. Thirty minutes after instillation of 0.125% pilocarpine in both eyes, maximal and minimal pupil sizes reduced by 1.5 and 1.3 mm in the affected eye and 2.0 and 1.1 mm in the normal fellow eye (a-3 and a-4). In the patient who underwent 0.0625% pilocarpine testing, the normal fellow eye showed minimal change of maximal and minimal pupil diameters (0.1 mm and no change, respectively) (b-3 and b-4). On the contrary, maximal and minimal pupil diameters of the affected eye reduced by 1.5 and 1.4 mm, respectively. Note that the amount of change in anisocoria from baseline to post-pilocarpine test was 0.2 mm after instillation of 0.125% pilocarpine (a) and 1.4 mm after 0.0625% pilocarpine instillation (b). ACV = Average constriction velocity; ADV = Average dilation velocity; CON = Pupil constriction ratio; LAT = latency; MAX = maximal pupil diameter; MCV = Maximal constriction velocity; MIN = Minimal pupil diameter; T75 = Total time from the peak of constriction to the recovery of the pupil to 75% of maximal pupil diameter.

Figure 3

Comparison of the diagnostic ability of two concentrations of dilute pilocarpine for detecting unilateral Adie’s tonic pupil. (A) The area under the curve (AUC) of the change in anisocoria at darkness in response to pilocarpine instillation was 0.884 (95% confidence interval [CI], 0.778–0.952) in the 0.125% group and 0.952 (95% CI, 0.857–0.992) in the 0.0625% group (P = 0.168). In the 0.0625% group, a change in anisocoria ≧ 0.4 mm after topical pilocarpine instillation showed a sensitivity of 85.7% and a specificity of 90.9% for detecting unilateral Adie’s tonic pupil. (B) The AUC of the decrease in maximal pupil diameter in response to pilocarpine instillation was 0.840 (95% CI, 0.729–0.919) in the 0.125% group and 0.954 (95% CI, 0.855–0.993) in the 0.0625% group. The diagnostic efficacy of dilute pilocarpine for detecting unilateral Adie’s tonic pupil using a 0.0625% concentration was better than using a 0.125% concentration (P = 0.047), with a cutoff value of ≧ 0.5 mm pupillary constriction after pilocarpine instillation.