Efficacy of digital pupillometry for diagnosis of Horner syndrome

Abstract

Objectives: To evaluate the efficacy of digital pupillometry in the diagnosis of anisocoria related to Horner syndrome in adult patients.

Design: Retrospective, observational, case control study.

Methods: Nineteen patients with unilateral Horner syndrome (Horner group) and age-matched controls of 30 healthy individuals with normal vision and neither optic nerve dysfunction nor pupillary abnormalities were included. Pupillary light reflex (PLR) of the Horner group and controls were measured by a dynamic pupillometer (PLR-200; NeurOptics Inc., Irvine, USA). Minimal and maximal (min/max) pupil diameters, latency, constriction ratio, constriction velocity, dilation velocity, and total time taken by the pupil to recover 75% of maximal pupil diameter (T75) were noted. PLR were measured at baseline in both groups and at 30-45 minutes later after 0.5% apraclonidine (Iopidine®; Alcon Laboratories, Fort Worth, TX, USA) instillation in the Horner group.

Main outcome measures: The PLR parameters in the affected eye and inter-eye difference before and after 0.5% apraclonidine instillation.

Results: In the Horner group, pupil diameters and T75 showed significant difference between the affected eye and unaffected contralateral eye at baseline (all P<0.00625). Compared to controls, inter-eye difference values of pupil diameters and T75 were significantly larger in the Horner group (all P<0.001). After 0.5% apraclonidine instillation, changes in pupil diameter and constriction ratio were significantly larger in the affected eye compared to the unaffected contralateral eye (all P<0.00625). The area under the receiver operating characteristic curves for diagnosing Horner syndrome were largest for baseline inter-eye difference in min/max pupil sizes (AUC = 0.975, 0.994), T75 (AUC = 0.838), and change in min/max pupil sizes after apraclonidine instillation (AUC = 0.923, 0.929, respectively). The diagnostic criteria for Horner syndrome relying on baseline pupillary measurements was defined as one of the two major findings; 1) smaller maximal pupil diameter in the affected eye with an inter-eye difference of > 0.5 mm, or 2) T75 > 2.61 seconds in the affected eye, which showed a sensitivity of 94.7% and specificity of 93.3%. The diagnostic accuracy of apraclonidine testing showed a sensitivity of 84.6% and specificity of 92.3%.

Conclusions: Digital pupillometry is an objective method for quantifying PLR. Baseline inter-eye difference in maximal pupil sizes and dilation lag measured by T75 was equally effective in the diagnosis of Horner syndrome compared to the reversal of anisocoria after apraclonidine instillation.

Fig 1. Schematic diagram of the pupillary light response illustrating the recorded pupillary light reflex parameters.

1) maximal pupil diameter, 2) minimal pupil diameter, 3) pupil constriction ratio, 4) constriction latency, 5) average constriction velocity, 6) maximal constriction velocity, 7) average dilation velocity, 8) total time taken by the pupil to recover 75% of maximal pupil diameter.

Fig 2. Receiver operating characteristic curve of the baseline total time from the peak of constriction to the recovery of 75% of maximal pupil diameter (T75) and baseline inter-eye difference of T75.

The maximum area under the curve were 0.838 (95% Confidence interval (CI), 0.720 to 0.956; P < 0.0001) and 0.840 (95% CI, 0.702–0.978; P < 0.0001). With a cutoff value of T75> 2.61 sec, the sensitivity and specificity of the baseline T75 was 72.2% and 92.2%, respectively. As for the baseline inter-eye difference of T75, the sensitivity and specificity were 77.8% and 80.0% with a cutoff value of > 0.31 sec.

Fig 3. A patient diagnosed with iatrogenic Horner syndrome in the left eye after total thyroidectomy (A-F).

A, The patient at baseline, showing left ptosis and miosis; B, Thirty-five minutes after 1 drop of 0.5% apraclonidine instillation in both eyes. Note reversal of baseline anisocoria. C-F, Eight PLR parameters were presented with pupil response curves. The pupillary constriction ratio (CON) was defined as the minimal pupil diameter divided by the maximal pupil diameter, and the latency (LAT) as the time difference between initiation of retinal light stimulation and onset of pupillary constriction. Average constriction velocity (ACV), maximal constriction velocity (MCV), average dilation velocity (ADV) and total time taken by the pupil to recover 75% of maximal pupil diameter (T75) was also presented. C and D, Baseline pupil light reflex (PLR) curve measured with digital pupillometry in both affected eye (D) and contralateral normal eye (C). Note that inter-eye difference in maximal pupil diameter (6.0 mm in affected left eye and 6.6 mm in unaffected right eye), ADV and T75; ADV of the affected eyes (1.07 mm/sec) was slower than that of the unaffected eyes (1.13 mm/sec) and T75 of the affected eyes (2.87 sec) was longer compared with the unaffected eyes (2.07 sec). E and F, PLR curve after 0.5% apraclonidine instillation showed definite change of pupil diameter in affected eye compared to contralateral normal eye; the affected pupils showed an increase in maximal and minimal pupil diameter (6.8 mm and 5.2 mm, respectively) instead of decrease shown in contralateral unaffected eyes (5.1 mm and 3.2 mm, respectively). ADV of the affected eyes (0.73 mm/sec) was decreased and T75 of the affected eyes (3.10 sec) was increased after apraclonidine instillation.