Horizontal Saccadic Velocity in Patients with Exotropia before and after Unilateral Resection and Recession Surgery

Purpose The effects of strabismus surgery on eye movement are not known in detail, as few studies have compared saccade velocities before and after strabismus surgery. In this study, horizontal saccades were recorded using an eye-tracker in patients with only exotropia to compare the peak velocities (PVs), before and after undergoing strabismus surgery of the same type (unilateral resection and recession). Methods Horizontal saccades of monocular vision were recorded using an eye-tracking device in 18 patients with exotropia and 20 normal subjects. All patients were examined using the same method after strabismus surgery. Results The PVs of adduction and abduction in the patients were higher than those in the normal subjects (in dominant eye, P=0.032 for adduction and P=0.049 for abduction; in nondominant eye, P=0.016 for adduction and P=0.037 for abduction). Following the surgery, the PVs of abduction of the surgical eye (nondominant eye) decreased to the level of the normal subjects (P=0.016). However, there were no correlations between changes in the PVs and the extent of surgery (resection and recession). Conclusion Strabismus surgery normalized the patient's increased PV in the operated eye for abduction of horizontal saccade. Not only peripheral (extraocular muscle) but also central sensory-motor mechanisms may be involved in the changes in PV of horizontal saccades, both of which could result from the improvement of the primary eye position.


Introduction
Saccadic eye movements are important for rapid gaze shifting to visual targets. e peak velocity (PV) of saccades is an important parameter for saccade evaluation. e PV correlates with the amplitude of saccades, and the normal range of the PV has already been determined [1,2]. e PV of horizontal saccades reportedly reaches adult values by the age of 4.5 [3]. A previous study has reported no difference in the mean velocity of horizontal saccades between patients with horizontal strabismus and normal subjects [4].
However, few studies have compared saccade velocities before and after strabismus surgery [4,5]. Bucci et al. observed that the PV of horizontal saccades was significantly decreased after surgery for horizontal strabismus in some patients [5]. ey suggested that strabismus surgery improved the velocity of convergence and of divergence [4]. However, these previous studies have tested the effects of correcting the eye position on conjugate eye movements in mixed subject populations, including different types of strabismus and some operative methods. In the present study, horizontal saccades were recorded noninvasively, using an eye tracking system, in patients with only exotropia (XT), before and after undergoing strabismus surgery of the same type (unilateral resection and recession), as well as in normal subjects. To differentiate eye movement directions, the PV of horizontal saccades for adduction and abduction was calculated separately in each subject. e data were compared between the 2 groups (normal subjects vs. presurgical patients) and pairwise compared between the patients pre-and postsurgery.

Materials and Methods
e present study was approved by the Institutional Review Board of the University of Toyama (approval # 27-159) and conformed to all local laws and to the principles of the Declaration of Helsinki. Written informed consent was obtained from each participant after the experimental procedure was fully explained.
2.1. Participants. Twenty normal healthy adults (mean age: 29.9 years, range: 8-81 years, 8 women) and 18 patients with XT (mean age: 26.8 years, range: 6-80 years, 8 women) volunteered to participate in the study. All participants without dyscoria could clearly observe the visual target 40 cm away, with either the naked eye or soft contact lenses (corrected visual acuity of 1.0 or greater). All patients underwent surgery (resection of medial rectus muscle and recession of lateral rectus muscle) on their nondominant eyes, performed by 2 surgeons (MM and KF). e deviation angles near (30 cm) and far (5 m) were measured using the alternate prism cover test.
e dominant eye was determined using the hole-in-card test [6]. Patients with constant XT (acquired, concomitance, not consecutive) were considered eligible if exophoria (or orthophoria) and stereopsis, based on the Titmus stereo test, were achieved after the surgery. All patients were examined before and again 6-12 weeks after surgery.

Stimulus Presentation and Examination Paradigm.
e target consisted of a red inner circle (0.2°in diameter) superimposed at the center of a black circle (1.5°in diameter) and a white cross, in accordance with the study by aler et al. [7]. A computer monitor (Diamondcrysta ® , RDT222WM-S, Mitsubishi, Tokyo) displaying the target was located at 40 cm from the participant's eye. e monitor luminance was 190 cd/m 2 , the resolution was 1,680 × 1,050 pixels, and the refresh rate was 60 Hz. e participants sat on a chair in front of a table with their heads stabilized in a head positioner. ey were examined under the following two conditions: monocular viewing with the dominant eye and monocular viewing with the nondominant eye; the other, nonviewing eye covered by an infrared filter (IR-76 ® , Fujifilm, Tokyo, Japan). ey were instructed to fixate their gaze on a target located in the center at the beginning of the test trial, to fixate on the new target as rapidly as possible when it appeared at either 15°rightward or 15°leftward randomly, and finally to return their gaze to the original, center location when the latter target disappeared. Each subject performed five trials in each direction (adduction and abduction), with exclusion of saccade trials that included blinks or incorrect responses. A limited number of trials were used, as patients were examined during consultation hours and some participants were young children.

Eye Movement Recording.
e horizontal (X) and vertical (Y) positions of both eyes were recorded using the ViewPoint EyeTracker ® system (Arrington Research, Scottsdale, AZ, USA) at a sampling rate of 220 Hz, in accordance with the study by Crossland et al. [8][9][10][11]. is system consisted of two infrared cameras mounted on the head positioner, which sent images of the eye to a computer via a USB cable. e eye tracker recorded the subject's eye positions using the dark-pupil technique. ese data were stored on a hard disk for offline data analysis. Prior to fixation stability testing, a 9-point grid (3 × 3 matrix) calibration and a subsequent validation procedure were performed for each subject using software supplied by the eye-tracker manufacturer (ViewPoint EyeTracker Software User Guide).

Data Analysis and Statistics.
In the present study, only primary saccades, and not corrective saccades, were analyzed. e maximum value of the velocity waveform obtained from the primary differential values of the eye position in a saccade was defined as the PV. e onset of a primary saccade was defined as the time when the eye velocity exceeded 5% of the saccadic PV; the offset was set to when the eye velocity dropped below 10°/s, as is the previously reported standard [3,4]. Data of eye movements that were in the wrong direction or that were contaminated with blinks were discarded. For each participant, the PVs (mean of 5 trials) for adduction and abduction of each eye were calculated.
e Mann-Whitney U test was used to compare the PVs for each dominant and nondominant eye between normal subjects and patients with XT, presurgically. e Wilcoxon signed-rank nonparametric test for paired samples was used to compare the PVs between pre and postsurgical parameters in patients with XT. For patients with XT, Spearman's rank-correlation between changes in the PV in the operated (nondominant) eye and the amount of surgery (resection or recession) was calculated. e JMP ® statistical software package (SAS Institute, Cary, NC, USA) was used for the above tests; the significance level was set at P < 0.05.

Comparison of the PVs between Normal Subjects and
Patients with XT. Figure 1 shows monocular recordings of typical sequences of horizontal saccades for a normal subject (gray symbols) and a patient with XT before surgery (black symbols). e shape of the primary saccade was smooth for most subjects in both groups, although some patients with XT sometimes exhibited overshoot Figure 1(b). e number of cases in which the saccades overshoot their targets was one for adduction and five for abduction in the normal group. In patients with XT before surgery, overshoot was noted in six cases for adduction and eight for abduction. e corrective saccade, which appeared 180 msec after the end of the primary saccade, facilitated an eye position that could reach the target (15°rightward). e PV was significantly higher in the XT group than in the normal group, in either movement direction, for both eyes (Figure 2; in the dominant eye, P � 0.032 for adduction and P � 0.049 for abduction; in the nondominant eye, P � 0.016 for adduction and P � 0.037 for abduction).

PVs in Adduction and Abduction.
For adduction, the PVs in the dominant eye tended to reduce after the surgery, although the difference did not reach statistical significance (P � 0.55). No significant changes were observed in the nondominant eye (P � 0.21) (Figure 3). For abduction, there were no significant changes in the PVs in the dominant eye after the surgery (P � 0.39). e PVs in the nondominant eye clearly decreased after the surgery (P � 0.016), such that the mean PV value approached that of normal subjects (Figure 3). ere was no significant difference between the normal subjects and the patients with XT after surgery for abduction in the nondominant eye (P � 0.55).

Relationship between Changes in PVs and Extent of Surgery.
ere was no correlation between changes in the PVs and the extent of the surgery in the operated, nondominant eyes (adduction: rs � −0.006, P � 0.98; abduction: rs � −0.36, P � 0.14) (Figure 4).

Discussion
We here investigated the effect of strabismus surgery on saccade velocities and showed that this surgery decreased these patients' increased PV in the operated eye for abduction of horizontal saccade.
e PV of horizontal saccades in normal subjects was almost the same as that previously reported [1,2], while that in patients with XT was higher than that of the normal subjects, for both the dominant and nondominant eyes. It is presumed that the PVs were influenced by the accuracy of saccades (especially when overshoot saccades occurred), since the amplitude of saccades in patients with XT was slightly larger than in the normal subjects (data not shown). On the contrary, it is necessary to consider the cause due to the difference in the viewing condition. In a study by Niechwiej-Szwedo et al. [11], there was no significant difference in the PV of saccades between binocular viewing and monocular viewing in patients with horizontal strabismus without stereopsis, whereas in normal subjects and strabismus patients with stereopsis, the PV was lower during monocular viewing than during binocular viewing. Alternatively, as reported by Niechwiej-Szwedo et al. [11], the saccadic velocity in the normal subjects in the present study might have been decreased due to monocular viewing, because this was an unusual viewing condition for them. Conversely, the saccadic velocity of patients with XT, who were eligible for surgery, could not have been decreased because they had adapted to using monocular viewing over a long period of time. Difference of saccadic velocities between normal subjects and patients with XT could be caused by differences in both saccade accuracy and viewing condition.
Reduced tension of the extraocular muscles, which is the aim of strabismus surgery, may have resulted in changes of the PV. In the present study, however, there was no correlation between the changes in PVs after the surgery and the extent of resection/recession. In addition, the PV in adduction of the operated eye did not change after surgery. Kushner [12] performed a posterior fixation of the medial rectus in seven patients with convergence excess esotropia. ey observed that postoperative saccadic velocity testing did not reveal the expected decrease in saccadic velocity, as the eye moved increasingly into the field of action of the operated muscle [12]. Surgical effects on saccadic velocity are likely to be different between the lateral rectus muscle and the medial rectus muscle. Bucci et al. [4] observed that the PV of horizontal saccades was significantly decreased after surgery for horizontal strabismus in three of eight patients. However, the directions of horizontal saccades were not reported in their result. erefore, mechanisms other than extraocular (peripheral) factors are necessary to explain the change in the PV after surgery.
It has been reported that, in macaques with strabismus, the firing rate of neurons in the paramedian pontine reticular formation, the motor center for horizontal saccades, differed from that of normal monkeys [13]. Additionally, abnormal activities are observed in the abducens nucleus of macaques with strabismus [14]. erefore, the patients in our study may have had some abnormal activities in these oculomotor centers before surgery. Orthophoria or exophoria achieved by strabismus surgery could have influenced and improved the central sensory-motor mechanisms within a few months after the surgery, since binocular viewing became easier as a result of the corrected primary eye position. is would have resulted in reduced PV in abduction. Although the present study does not provide direct evidence for this speculation, both peripheral and central sensory-motor mechanisms may be involved in the changes in the PV of horizontal saccades, both of which could result from the improvement of the primary eye position. On the other hand, Pullela et al. [15], in their study using two monkeys with strabismus, reported that the immediate changes in ocular alignment, saccades, and smooth pursuit after strabismus surgery gradually reverted to presurgical levels by six months after surgery. ey concluded that immediate improvement in misalignment and changes in eye movement gains are likely due to contractility changes in the extraocular muscle, whereas longerterm effects are likely a combination of neural and muscle adaptation [15]. erefore, longitudinal evaluation of saccades after strabismus surgery in humans will need to include investigation of neural responses after peripheral remodeling, since the data obtained a few months after strabismus surgery in the present study indicated that PVs change during the process of remodeling of extraocular muscles that have undergone resection and recession surgery.

Conclusions
e PVs of horizontal saccades in patients with exotropia were higher than those in the normal subjects. Following the surgery, the PVs of abduction of the surgical eye decreased to the level of the normal subjects; however, those of adduction were not changed. Also, there were no correlations between changes in the PVs and the extent of surgery. erefore, not only peripheral (extraocular muscle) but also central sensory-motor mechanisms may be involved in the changes in PV of horizontal saccades, both of which could result from the improvement of the primary eye position.
Longitudinal evaluation of saccades after strabismus surgery is necessary to investigate neural responses after peripheral remodeling in patients with strabismus.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.