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Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery
Journal Pre-proof Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery Miharu Mihara, MD, Atsushi Hayashi, MD, Ken Kakeue, Ryoi Tamura, MD, PhD PII:
S1091-8531(20)30004-5
DOI:
https://doi.org/10.1016/j.jaapos.2019.09.017
Reference:
YMPA 3120
To appear in:
Journal of AAPOS
Received Date: 16 April 2019 Revised Date:
8 September 2019
Accepted Date: 16 September 2019
Please cite this article as: Mihara M, Hayashi A, Kakeue K, Tamura R, Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery, Journal of AAPOS (2020), doi: https://doi.org/10.1016/j.jaapos.2019.09.017. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery Miharu Mihara, MD,a,b Atsushi Hayashi, MD,a Ken Kakeue,a and Ryoi Tamura, MD, PhDb Author affiliations: aDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; bDepartment of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Submitted April 16, 2019. Revision accepted September 17, 2019. Correspondence: Dr. Ryoi Tamura, Department of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 9300194, Japan (email: [email protected]). Word count: 2,952 Abstract only: 228
Abstract Purpose To observe the change in horizontal smooth pursuit in patients with intermittent exotropia before and after strabismus surgery. Methods The smooth pursuit of patients with intermittent exotropia was recorded using a video eyetracker before and 1 week, and 1, 3, and 6 months after strabismus surgery. Subjects were asked to track a step-ramp target moving at ±6.1°/sec horizontally as accurately as possible under binocular viewing. The differences in gain (eye velocity divided by target velocity) and amplitude of smooth pursuit between right and left eyes before and after surgery were compared. Results A total of 9 patients (mean age, 22.2 ± 13.9 years) were included. Mean preoperative ocular alignment at near was 59.1∆ ± 34.7∆. The difference in gain between the left and right eyes before surgery was 0.23 ± 0.1; in amplitude, 3.0° ± 3.7°. These values were improved at 1 week after surgery (gain, 0.08 ± 0.06; amplitude, 0.9° ± 0.65°) and continued to improve for 6 months after surgery; however, ocular alignment at near reverted from 5.9∆ ± 10.5∆ to 18.9∆ ± 17.5∆ by 6 months after surgery. Conclusions In this small patient cohort, surgical correction of ocular alignment improved binocular coordination of smooth pursuit in intermittent exotropia. In the long term, the improvement of the binocular coordination of smooth pursuit tended to remain, although the eye position partially reverted to the presurgical state.
The smooth pursuit system is an oculomotor control mechanism that facilitates smooth movement of the eyes when following a moving target to stabilize the retinal image. The system has usually been characterized as a negative feedback controller, where motion of the retinal image is the stimulus that drives the smooth eye movement. Because an image must be both still on the retina and near the fovea for highest acuity, both the velocity and the position of the retinal image must be controlled when the subject visually tracks a moving target.1 Lions and colleagues2 reported that the binocular coordination of smooth pursuit in children with strabismus (early onset or acquired esotropia, intermittent or constant exotropia) was worse than that in normal-seeing children and children with vergence deficits having binocular vision. In addition, they found that binocular coordination of smooth pursuit in children with vergence deficits was abnormal. They concluded that binocular vision plays an important role in improving binocular coordination of pursuit. Von Noorden and colleagues3 reported that the smooth sinusoidal eye position profiles were superseded by quick saccadic jumps at lower pursuit frequencies in patients with strabismic amblyopia. On the other hand, Ono and colleagues4 suggested that monkeys with strabismus retained the ability to produce conjugate adaptation of smooth pursuit and that a single central representation of retinal motion information in the viewing eye drove adaptation for both eyes equally. Few studies have compared binocular coordination of smooth pursuit before and after strabismus surgery. An experimental study involving 2 monkeys with exotropia showed that changes in smooth pursuit gain immediately after surgery returned to the preoperative levels by 6 months postoperatively.5 Longitudinal changes in smooth pursuit following strabismus surgery have not been studied in humans. In previous studies on smooth pursuit related to strabismus, an abnormal saccadic substitution response appeared to be related to the presence of amblyopia
rather than strabismus.3,6 A different study2 reported that binocular vision function could be required to maintain binocular coordination of smooth pursuit.2 Moreover, normal binocular function is maintained by heterophoria or orthophoria, meaning that binocular visual function is required for coordination of smooth pursuit and can be affected indirectly by both amblyopia and strabismus. The present study aimed to observe the change in horizontal smooth pursuit in patients with intermittent exotropia without amblyopia before and after strabismus surgery. Subjects and Methods This study was approved by the Institutional Review Board of the University of Toyama 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. For patients <20 years of age, written informed consent was obtained from a guardian. Patients at least 5 years of age with intermittent exotropia who were scheduled to undergo strabismus surgery were recruited to participate in the study. All patients underwent surgery (unilateral resection of the medial rectus muscle and recession of the lateral rectus muscle in the nondominant eye, or bilateral lateral rectus muscle recession). All surgical procedures were performed by the same surgeon (MM). The control of the intermittent exotropia was determined clinically using the monocular cover-uncover test. Control was deemed poor if exotropia manifested spontaneously or if there was any disruption of fusion without recovery after the cover-uncover testing. Good control was defined as exotropia manifested only after the cover testing and resumed fusion immediately with or without blinking or refixation. The deviation angles at near (30 cm) and distance (5 m) were measured using the alternate prism cover test. Stereopsis was evaluated using the Titmus stereo test; a break point of >5 cm from the nose was considered poor convergence.7 Patients
were included if there was an exodeviation angle of ≥15∆ at near and at distance on alternate prism cover testing. Furthermore, patients with constant exotropia (acquired, concomitant, not consecutive) were eligible for inclusion if the eye position indicated heterophoria or orthophoria after surgery and the Titmus stereo test confirmed stereopsis of 400 arcsec. All participants without dyscoria could clearly observe the visual target 40 cm away with either the naked eye or using soft contact lenses (corrected visual acuity of at least 1.0). Patients with other eye diseases, a neurologic or systemic disease, or eye movement disorders were excluded. All patients were examined before surgery and 1 week, and 1, 3, and 6 months after surgery. Stimulus Presentation and Examination Paradigm The visual motion target was a white Gaussian spot with a diameter of 0.5° and luminance of 117 cd/m2, presented on a uniform gray background (70 cd/m2) in accordance with the method used by Ke and colleagues.8 A computer monitor (Diamondcrysta, RDT222WM-S, Mitsubishi, Tokyo) displaying the target was located 40 cm from the participant’s eye. The monitor resolution was 1680 × 1050 pixels, with a refresh rate of 60 Hz. Participants were seated in front of a table, with their heads stabilized in a head positioner; examination took place under binocular viewing conditions. Each trial started with central fixation. Participants were asked to track as accurately as possible a step-ramp target moving at ±6.1°/sec horizontally. The step-ramp method was used to prevent early saccades in smooth pursuit, as described by Rashbass9 and Sakuma and colleagues.10 The step amplitude was 0.85°. The motion target was initially displaced in the direction opposite to the target’s velocity step before moving back across the fovea ramp. The motion target moved from the center to either 18.3° leftward or 18.3° rightward. The direction was randomized across trials. Each subject performed 5 trials in each direction. Smooth pursuit trials that included blinks, saccades
(with the exclusion of catch-up saccades), or incorrect responses were excluded. A limited number of trials were performed because the patients were examined during consultation hours, and some of the study participants were young children. Eye Movement Recording The horizontal (X) and vertical (Y) positions of each eye were recorded using the ViewPoint EyeTracker system (Arrington Research, Scottsdale, AZ) at a sampling rate of 350 Hz. The system consisted of 2 infrared cameras mounted on the head positioner. The eye tracker recorded the subject’s eye positions using the dark-pupil technique. Prior to testing of smooth pursuit, a 9point grid (3 × 3 matrix) calibration and a subsequent validation procedure were performed for each subject using the software supplied by the eye-tracker manufacturer (ViewPoint EyeTracker Software User Guide). Data Analysis and Statistics The means of the differences between the left and right eyes in the gain, that is, eye velocity divided by target velocity (DiffL-R gain), and amplitude (DiffL-R amplitude) of smooth pursuit across 5 trials in each trial type (leftward and rightward pursuit) were calculated for each participant. The Friedman test was performed to detect the effects at 1week before, and 1, 3, and 6 months after strabismus surgery. If the difference was significant , pairwise comparisons were performed using a Wilcoxon signed-rank test with Bonferroni correction. The correlations of DiffL-R gain and DiffL-R amplitude values with the ocular deviation at near using all pre- and postsurgery data were analyzed. We also analyzed the correlation of pre- and postsurgical changes in DiffL-R gain and DiffL-R amplitude with pre- and postoperative changes in the ocular deviation at near (in this analysis, only values of each parameter 6 months after surgery were used as postoperative data). Spearman’s rank-correlation was used for these correlation analyses.
The Friedman test was performed using IBM SPSS for Windows statistics (version 21.0, IBM Corp, Armonk, NY). The remaining statistical analyses were performed using the JMP Pro software package (version 11. 2.0, SAS Institute, Cary, NC). The significance level was set at P < 0.05. Results A total of 9 patients (mean age: 22.2 ± 13.9 years, 10-45 years, 7 females) were included (Table 1). Longitudinal Changes in Ocular Deviation and Sensory Outcome One patient (11%) had constant exotropia (poor control of the intermittent exotropia) at preoperative examinations. The other 8 patients (89%) had nonconstant exotropia. Patient 2 had good control of the intermittent exotropia for the entire duration of the preoperative examination. Seven patients sometimes had constant exotropia during the examination but did achieve refusion by blinking or refixation. The preoperative mean exodeviation angles (mean and standard deviation) at near was 59.1∆ ± 34.7∆ (range, 18∆-113∆); at distance, 50∆ ± 19.5∆ (range, 25∆-80∆). See Table 1. One week after surgery, the mean deviation at near was 5.9∆ ± 10.5∆ (range, −14∆-18∆); at distance, 1.8 ± 6.4∆ (range, −10∆-12∆). However, the ocular deviations at near and distance regressed to 18.9∆ ± 17.5∆ (range, 2∆-57∆) and 14.8 ± 15.5∆ (range, 2∆-50∆), respectively, by 6 months after surgery (Table 1, Figure 1). Before surgery stereopsis at near varied from 40 to nil (>3000 arcsec). Four of 9 patients had good stereopsis (≥60 arcsec). After surgery, the stereopsis of all patients was improved or equal to before surgery. Seven patients had good stereopsis (≥60 arcsec). A patient who had no stereopsis before surgery had stereopsis of 400 arcsec postoperatively. Fusion was examined using synoptophore preoperatively, but not postoperatively. Four patients (4, 6, 7, and 9) did not
have fusion before surgery. Other patients had a wide range of fusion, except for patient 5, who had a narrow range of fusion before surgery (Table 1). Longitudinal Changes in Smooth Pursuit In the presurgical data, mean DiffL-R gain was 0.23 ± 0.1; the mean DiffL-R amplitude, 3.0° ± 3.7°. These values were improved at 1 week after surgery (gain, 0.08 ± 0.06; amplitude, 0.9° ± 0.65°) and remained improved for 6 months postoperatively. The values of DiffL-R gain were significantly improved at 3 and 6 months postoperatively (Friedman test, χ2 = 11.64; df = 4; P = 0.013; Wilcoxon signed-rank test with Bonferroni correction at 1 week and 1, 3, and 6 months, P = 0.15, P = 0.08, P = 0.016, P = 0.016, resp.; Figure 2A), although the values of DiffL-R amplitude did not reach statistical significance at any assessment time after surgery (Friedman test, χ2 = 8.0; df = 4; P = 0.09; Figure 2B). Figure 3A-B shows a trajectory of both eye positions for patient 1, with intermittent exotropia before and after surgery. Although the smooth pursuit for the patient initially showed good binocular coordination, disconjugacy of pursuit was revealed midway during smooth pursuit due to expression of exotropia (Figure 3A, small arrows). Because the patient remained orthophoric during smooth pursuit after surgery, binocular coordination of smooth pursuit was improved; however, his binocular coordination of catch-up saccades during smooth pursuit was fine even before surgery. Patient 2 consistently had good control of the exodeviation at near before and after surgery. Her binocular coordination of smooth pursuit was good during the pursuit examination before surgery (Figure 3C). After surgery, her good binocular coordination of smooth pursuit was maintained and her pursuit eye movement was smoother than before surgery because of a decreasing number of large catch-up saccades (Figure 3D). Patient 9 had constant exotropia at near and distance before surgery but good control of the exodeviation after surgery. Before surgery, there was a marked difference in
pursuit amplitude between both eyes, because she fixed her left eye to the target and her right eye deviated outward (Figure 3E,F). Relationships between Smooth Pursuit and Ocular Alignment The correlations between ocular deviation and DiffL-R amplitude and DiffL-R gain were significant (ocular deviation vs DiffL-R amplitude, ρ = 0.47 and P < 0.05; ocular deviation vs DiffL-R gain, ρ = 0.6 and P < 0.05). See Figure 4A,B. There were no correlations between preand postoperative changes in the amount of ocular deviation and pre- and postoperative changes in DiffL-R amplitude or those in DiffL-R gain (DiffL-R amplitude versus ocular deviation, ρ = 0.046 and P = 0.86; DiffL-R gain vs ocular deviation, ρ = −0.311 and P = 0.21). Discussion In our patient cohort, the DiffL-R gain and DiffL-R amplitude were significantly decreased after strabismus surgery; that is, the binocular coordination of smooth pursuit improved postoperatively. Moreover, the improvement tended to persist for at least 6 months. Some aspects of the surgical outcomes, including changes in ocular deviation and binocular visual function, may be involved in this improvement. As a result of the postoperative improvement in deviation angle, which leads to a mechanically balanced position of the left and right eyes, binocular coordination of smooth pursuit (ie, DiffL-R gain and DiffL-R amplitude) seems to be improved. The value of the DiffL-R gain and DiffL-R amplitude, which are decreased immediately after surgery, should increase as the deviation angle returns to the preoperative level. It is known that intermittent exotropia in humans recurs frequently in the long term after strabismus surgery.11,12 Consistent with this, in many of our patients, the ocular deviation angle more or less reverted toward the presurgical level during the 6 months after surgery, while the improvement in binocular coordination of
smooth pursuit tended to persist during this period. Therefore, the improvement of deviation angle may be less important for maintaining binocular coordination of smooth pursuit in the long term. We hypothesize that binocular coordination of smooth pursuit is determined by the patient’s ability to maintain heterophoria and binocular vision during examination of smooth pursuit. Pullela and colleagues5 reported that the changes in smooth pursuit gain noted immediately after surgery returned to preoperative levels by 6 months after surgery in monkeys with exotropia. Their experiment used 2 monkeys that had no binocular vision function because of artificial exotropia induced by prism goggles in infancy (the sensitive period of binocular vision development). In contrast, in the present study, most patients showed an increased ability to maintain periods of orthophoria after surgery. This indicates, in agreement with the findings of Lions and colleagues,2 that the maintenance of orthophoria during smooth pursuit and improvement in binocular vision function could influence the improvement in binocular coordination of smooth pursuit. Although the exodeviation angle reverted postoperatively over the long term, the maintenance of orthophoria during smooth pursuit and normal binocular vision could lead to continued improvement in binocular coordination of smooth pursuit. To support this hypothesis, cases of infantile exotropia (or infantile esotropia) without normal binocular vision must be compared before and after strabismus surgery. In the present study, DiffL-R amplitude and DiffL-R gain were correlated with the ocular deviation angle. The DiffL-R amplitude and DiffL-R gain were proportional to the exodeviation angle measured by alternate prism cover testing, when some patients showed exotropia during examination of smooth pursuit (see Figure 3A [patient 1], E [patient 9]). However, the DiffL-R amplitude and DiffL-R gain were small when the patient showed orthophoria during examination
of smooth pursuit, as seen in patient 2 (Figure 3C), even if the patient showed a large exodeviation. It is likely that a large deviation angle made it difficult to maintain orthophoria during smooth pursuit, as in patient 1 (Figure 3A). Therefore, it is likely that the DiffL-R amplitude and DiffL-R gain are correlated with the ocular deviation angle indirectly via the duration of orthophoria. The changes in DiffL-R amplitude and DiffL-R gain achieved by strabismus surgery were not correlated with the extent of improvement in deviation angle. These outcomes might be attributable to the influence of the data from patients with good binocular vision function despite large ocular deviation angles before surgery (patients 3 and 8). The values of the DiffL-R amplitude and DiffL-R gain before surgery were small in these patients, that is, binocular coordination in smooth pursuit was good, because they maintained orthophoria during smooth pursuit. Therefore, the changes in DiffL-R amplitude and DiffL-R gain achieved by surgery may not have been proportional to the extent of improvement in deviation angle. Furthermore, the small number of data on the change in DiffL-R amplitude and DiffL-R gain before and after surgery (ie, before vs 6 months after surgery) may have weakened the statistical power of the study to detect a significant correlation. Studies that include these examinations in a larger number of subjects will be needed to obtain solid evidence on this correlation. The limitations of this study include the wide range of patient ages and the small number of cases. Furthermore, the patients included had varying ocular deviation angles. Therefore, our conclusions are offered with caution. Moreover, the relationship between the change in smooth pursuit after surgery and the changes in ocular deviation angle and binocular vision function after surgery must be monitored for more than 6 months to determine whether or not improvement of binocular coordination persists.
References 1.
Carl JR, Gellman RS. Human smooth pursuit: stimulus-dependent response. J Neurophysiol 1987;57:1446-63.
2.
Lions C, Bui-Quoc E, Wiener-Vacher S, Seassau M, Bucci MP. Smooth pursuit eye movements in children with strabismus and in children with vergence deficits. PLoS One 2013;8:e83972.
3.
Von Noorden GK, Mackensen G. Pursuit movements of normal and amblyopic eyes. An electro-ophthalmographic study. Ⅱ. Pursuit movements in amblyopic patients. Am J Ophthalmol 1962;53:477-87.
4.
Ono S, Das VE, Mustari MJ. Conjugate adaptation of smooth pursuit during monocular viewing in strabismic monkeys with exotropia. Invest Ophthalmol Vis Sci 2012;53:203845.
5.
Pullela M, Degler BA, Coats DK, Das VE. Longitudinal evaluation of eye misalignment and eye movements following surgical correction of strabismus in monkeys. Invest Ophthalmol Vis Sci 2016;57:6040-47.
6.
Ciuffreda KJ, Kenyon RV, Stark L. Abnormal saccadic substitution during smallamplitude pursuit tracking in amblyopic eyes. Invest Ophthalmol Vis Sci 1979;18:50616.
7.
Scheiman M, Gallaway M, Frantz KA, et al. Nearpoint of convergence: test procedure, target selection, and normative data. Optom Vis Sci 2003;80:214-25.
8.
Ke SR, Lam J, Pai DK, Spering M. Directional asymmetries in human smooth pursuit eye movements. Invest Ophthalmol Vis Sci 2013;54:4409-21.
9.
Rashbass BC. The relationship between saccadic and smooth tracking eye movements.
J Physiol 1961;159:326-38. 10.
Sakuma A, Ogino S, Takahashi K, Kato I. Aging effects upon smooth pursuit induced by step-ramp stimulation. Auris Nasus Larynx 2000;27:195-200.
11.
Beneish R, Flanders M. The role of stereopsis and early postoperative alignment in longterm surgical results of intermittent exotropia. Can J Ophthalmol 1994;29:119-24.
12.
Koklanis K, Georgievski Z. Recurrence of intermittent exotropia: factors associated with surgical outcomes. Strabismus 2009;17:37-40.
Legends FIG 1. Binocular alignment at near (A) and distance (B) for each patient. Solid lines indicate each individual; mean for all patients is indicated by the dashed line with solid circles. The time points are before surgery (Pre) and 1 week (1W), and 1, 3, and 6 months (1M, 3M, 6M) after surgery. FIG 2. Comparison of differences in gain (A) and amplitude (B) between eyes. The white box indicates the preoperative difference. The shaded box indicates the difference at 1 week postoperatively; the gray box, at 1 month; the dotted box, at 3 months; and the light gray box, at 6 months. Horizontal black lines within each box indicate median values. Boxes extend from the 25th to the 75th percentile of each period; upper and lower lines indicate maximum and minimum values. The differences in gain and amplitude between eyes were significantly improved at all assessment times after surgery. *P < 0.05. FIG 3. Typical examples (patients 1, 2, 9) of smooth pursuit for the right eye (solid light gray line) and left eye (solid gray line) waveform. Eye position during smooth pursuit before surgery (patients 1 [A], 2 [C], and 9 [E]) and 1 month after surgery (patients 1 [B], 2 [D], and 9 [F]). Patient 1 had weak orthophoria that switched to exotropia while tracking the target without covering one eye before surgery. Patient 2 had good control of the exodeviation at near before and after surgery. Patient 9 had constant exotropia at near and distance before surgery, although she could have good control of the exodeviation after surgery. The small arrow indicates the beginning of the time that disconjugacy of pursuit was evident. FIG 4. A, Relationship between difference in gain and ocular deviation, showing a correlation. B, Relationship between difference in amplitude and ocular deviation, also showing a correlation.
Table 1. Summary of patients with exotropia No. Age, Sex years 1 2 3 4 5 6 7 8 9
12 12 29 10 10 31 12 39 45
M F F F M F F F F
Surgery, mm
LE MR 6.5, LR 6.5 BE LR 5.0 RE MR 5.5, LR 5.5 RE MR 6.5, LR 6.5 RE MR 6.5, LR 6.0 LE MR 6.5, LR 8.0 LE MR 5.0, LR 4.5 RE MR 7.0, LR 8.0 RE MR 8.0, LR 9.0
Deviation at near, PDa Pre 40 18 80 45 30 86 25 113 95
1W 6 4 16 −1 −14 6 0 18 18
6M 20 6 10 8 2 20 12 57 35
Deviation at distance, a PD Pre 1W 6M 40 8 16 35 2 4 60 6 6 45 −1 4 30 −10 2 63 2 20 25 -2 6 72 12 50 80 −1 25
Convergence
Stereopsis, arcsec Fusion range, deg Before After Before After Pre Good Good 40 40 −15 to +10 Good Good 40 40 −13 to +40 Good Good 80 40 −15 to +22 Good Good 140 40 — Poor Good 40 40 −2 to +9 Good Good 3000 100 — Good Good 140 50 — Good Good 50 40 −25 to +30 Poor Good >3000 400 —
BE, both eyes; LE, left eye; LR, lateral rectus; MR, medial rectus muscle; RE, right eye muscle; PD, prism diopter. a
Pre-, before surgery; 1W, 1 week after surgery; 6M, 6 months after surgery.
S1091-8531(20)30004-5
DOI:
https://doi.org/10.1016/j.jaapos.2019.09.017
Reference:
YMPA 3120
To appear in:
Journal of AAPOS
Received Date: 16 April 2019 Revised Date:
8 September 2019
Accepted Date: 16 September 2019
Please cite this article as: Mihara M, Hayashi A, Kakeue K, Tamura R, Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery, Journal of AAPOS (2020), doi: https://doi.org/10.1016/j.jaapos.2019.09.017. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Longitudinal changes in binocular coordination of smooth pursuit in patients with intermittent exotropia after strabismus surgery Miharu Mihara, MD,a,b Atsushi Hayashi, MD,a Ken Kakeue,a and Ryoi Tamura, MD, PhDb Author affiliations: aDepartment of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; bDepartment of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Submitted April 16, 2019. Revision accepted September 17, 2019. Correspondence: Dr. Ryoi Tamura, Department of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 9300194, Japan (email: [email protected]). Word count: 2,952 Abstract only: 228
Abstract Purpose To observe the change in horizontal smooth pursuit in patients with intermittent exotropia before and after strabismus surgery. Methods The smooth pursuit of patients with intermittent exotropia was recorded using a video eyetracker before and 1 week, and 1, 3, and 6 months after strabismus surgery. Subjects were asked to track a step-ramp target moving at ±6.1°/sec horizontally as accurately as possible under binocular viewing. The differences in gain (eye velocity divided by target velocity) and amplitude of smooth pursuit between right and left eyes before and after surgery were compared. Results A total of 9 patients (mean age, 22.2 ± 13.9 years) were included. Mean preoperative ocular alignment at near was 59.1∆ ± 34.7∆. The difference in gain between the left and right eyes before surgery was 0.23 ± 0.1; in amplitude, 3.0° ± 3.7°. These values were improved at 1 week after surgery (gain, 0.08 ± 0.06; amplitude, 0.9° ± 0.65°) and continued to improve for 6 months after surgery; however, ocular alignment at near reverted from 5.9∆ ± 10.5∆ to 18.9∆ ± 17.5∆ by 6 months after surgery. Conclusions In this small patient cohort, surgical correction of ocular alignment improved binocular coordination of smooth pursuit in intermittent exotropia. In the long term, the improvement of the binocular coordination of smooth pursuit tended to remain, although the eye position partially reverted to the presurgical state.
The smooth pursuit system is an oculomotor control mechanism that facilitates smooth movement of the eyes when following a moving target to stabilize the retinal image. The system has usually been characterized as a negative feedback controller, where motion of the retinal image is the stimulus that drives the smooth eye movement. Because an image must be both still on the retina and near the fovea for highest acuity, both the velocity and the position of the retinal image must be controlled when the subject visually tracks a moving target.1 Lions and colleagues2 reported that the binocular coordination of smooth pursuit in children with strabismus (early onset or acquired esotropia, intermittent or constant exotropia) was worse than that in normal-seeing children and children with vergence deficits having binocular vision. In addition, they found that binocular coordination of smooth pursuit in children with vergence deficits was abnormal. They concluded that binocular vision plays an important role in improving binocular coordination of pursuit. Von Noorden and colleagues3 reported that the smooth sinusoidal eye position profiles were superseded by quick saccadic jumps at lower pursuit frequencies in patients with strabismic amblyopia. On the other hand, Ono and colleagues4 suggested that monkeys with strabismus retained the ability to produce conjugate adaptation of smooth pursuit and that a single central representation of retinal motion information in the viewing eye drove adaptation for both eyes equally. Few studies have compared binocular coordination of smooth pursuit before and after strabismus surgery. An experimental study involving 2 monkeys with exotropia showed that changes in smooth pursuit gain immediately after surgery returned to the preoperative levels by 6 months postoperatively.5 Longitudinal changes in smooth pursuit following strabismus surgery have not been studied in humans. In previous studies on smooth pursuit related to strabismus, an abnormal saccadic substitution response appeared to be related to the presence of amblyopia
rather than strabismus.3,6 A different study2 reported that binocular vision function could be required to maintain binocular coordination of smooth pursuit.2 Moreover, normal binocular function is maintained by heterophoria or orthophoria, meaning that binocular visual function is required for coordination of smooth pursuit and can be affected indirectly by both amblyopia and strabismus. The present study aimed to observe the change in horizontal smooth pursuit in patients with intermittent exotropia without amblyopia before and after strabismus surgery. Subjects and Methods This study was approved by the Institutional Review Board of the University of Toyama 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. For patients <20 years of age, written informed consent was obtained from a guardian. Patients at least 5 years of age with intermittent exotropia who were scheduled to undergo strabismus surgery were recruited to participate in the study. All patients underwent surgery (unilateral resection of the medial rectus muscle and recession of the lateral rectus muscle in the nondominant eye, or bilateral lateral rectus muscle recession). All surgical procedures were performed by the same surgeon (MM). The control of the intermittent exotropia was determined clinically using the monocular cover-uncover test. Control was deemed poor if exotropia manifested spontaneously or if there was any disruption of fusion without recovery after the cover-uncover testing. Good control was defined as exotropia manifested only after the cover testing and resumed fusion immediately with or without blinking or refixation. The deviation angles at near (30 cm) and distance (5 m) were measured using the alternate prism cover test. Stereopsis was evaluated using the Titmus stereo test; a break point of >5 cm from the nose was considered poor convergence.7 Patients
were included if there was an exodeviation angle of ≥15∆ at near and at distance on alternate prism cover testing. Furthermore, patients with constant exotropia (acquired, concomitant, not consecutive) were eligible for inclusion if the eye position indicated heterophoria or orthophoria after surgery and the Titmus stereo test confirmed stereopsis of 400 arcsec. All participants without dyscoria could clearly observe the visual target 40 cm away with either the naked eye or using soft contact lenses (corrected visual acuity of at least 1.0). Patients with other eye diseases, a neurologic or systemic disease, or eye movement disorders were excluded. All patients were examined before surgery and 1 week, and 1, 3, and 6 months after surgery. Stimulus Presentation and Examination Paradigm The visual motion target was a white Gaussian spot with a diameter of 0.5° and luminance of 117 cd/m2, presented on a uniform gray background (70 cd/m2) in accordance with the method used by Ke and colleagues.8 A computer monitor (Diamondcrysta, RDT222WM-S, Mitsubishi, Tokyo) displaying the target was located 40 cm from the participant’s eye. The monitor resolution was 1680 × 1050 pixels, with a refresh rate of 60 Hz. Participants were seated in front of a table, with their heads stabilized in a head positioner; examination took place under binocular viewing conditions. Each trial started with central fixation. Participants were asked to track as accurately as possible a step-ramp target moving at ±6.1°/sec horizontally. The step-ramp method was used to prevent early saccades in smooth pursuit, as described by Rashbass9 and Sakuma and colleagues.10 The step amplitude was 0.85°. The motion target was initially displaced in the direction opposite to the target’s velocity step before moving back across the fovea ramp. The motion target moved from the center to either 18.3° leftward or 18.3° rightward. The direction was randomized across trials. Each subject performed 5 trials in each direction. Smooth pursuit trials that included blinks, saccades
(with the exclusion of catch-up saccades), or incorrect responses were excluded. A limited number of trials were performed because the patients were examined during consultation hours, and some of the study participants were young children. Eye Movement Recording The horizontal (X) and vertical (Y) positions of each eye were recorded using the ViewPoint EyeTracker system (Arrington Research, Scottsdale, AZ) at a sampling rate of 350 Hz. The system consisted of 2 infrared cameras mounted on the head positioner. The eye tracker recorded the subject’s eye positions using the dark-pupil technique. Prior to testing of smooth pursuit, a 9point grid (3 × 3 matrix) calibration and a subsequent validation procedure were performed for each subject using the software supplied by the eye-tracker manufacturer (ViewPoint EyeTracker Software User Guide). Data Analysis and Statistics The means of the differences between the left and right eyes in the gain, that is, eye velocity divided by target velocity (DiffL-R gain), and amplitude (DiffL-R amplitude) of smooth pursuit across 5 trials in each trial type (leftward and rightward pursuit) were calculated for each participant. The Friedman test was performed to detect the effects at 1week before, and 1, 3, and 6 months after strabismus surgery. If the difference was significant , pairwise comparisons were performed using a Wilcoxon signed-rank test with Bonferroni correction. The correlations of DiffL-R gain and DiffL-R amplitude values with the ocular deviation at near using all pre- and postsurgery data were analyzed. We also analyzed the correlation of pre- and postsurgical changes in DiffL-R gain and DiffL-R amplitude with pre- and postoperative changes in the ocular deviation at near (in this analysis, only values of each parameter 6 months after surgery were used as postoperative data). Spearman’s rank-correlation was used for these correlation analyses.
The Friedman test was performed using IBM SPSS for Windows statistics (version 21.0, IBM Corp, Armonk, NY). The remaining statistical analyses were performed using the JMP Pro software package (version 11. 2.0, SAS Institute, Cary, NC). The significance level was set at P < 0.05. Results A total of 9 patients (mean age: 22.2 ± 13.9 years, 10-45 years, 7 females) were included (Table 1). Longitudinal Changes in Ocular Deviation and Sensory Outcome One patient (11%) had constant exotropia (poor control of the intermittent exotropia) at preoperative examinations. The other 8 patients (89%) had nonconstant exotropia. Patient 2 had good control of the intermittent exotropia for the entire duration of the preoperative examination. Seven patients sometimes had constant exotropia during the examination but did achieve refusion by blinking or refixation. The preoperative mean exodeviation angles (mean and standard deviation) at near was 59.1∆ ± 34.7∆ (range, 18∆-113∆); at distance, 50∆ ± 19.5∆ (range, 25∆-80∆). See Table 1. One week after surgery, the mean deviation at near was 5.9∆ ± 10.5∆ (range, −14∆-18∆); at distance, 1.8 ± 6.4∆ (range, −10∆-12∆). However, the ocular deviations at near and distance regressed to 18.9∆ ± 17.5∆ (range, 2∆-57∆) and 14.8 ± 15.5∆ (range, 2∆-50∆), respectively, by 6 months after surgery (Table 1, Figure 1). Before surgery stereopsis at near varied from 40 to nil (>3000 arcsec). Four of 9 patients had good stereopsis (≥60 arcsec). After surgery, the stereopsis of all patients was improved or equal to before surgery. Seven patients had good stereopsis (≥60 arcsec). A patient who had no stereopsis before surgery had stereopsis of 400 arcsec postoperatively. Fusion was examined using synoptophore preoperatively, but not postoperatively. Four patients (4, 6, 7, and 9) did not
have fusion before surgery. Other patients had a wide range of fusion, except for patient 5, who had a narrow range of fusion before surgery (Table 1). Longitudinal Changes in Smooth Pursuit In the presurgical data, mean DiffL-R gain was 0.23 ± 0.1; the mean DiffL-R amplitude, 3.0° ± 3.7°. These values were improved at 1 week after surgery (gain, 0.08 ± 0.06; amplitude, 0.9° ± 0.65°) and remained improved for 6 months postoperatively. The values of DiffL-R gain were significantly improved at 3 and 6 months postoperatively (Friedman test, χ2 = 11.64; df = 4; P = 0.013; Wilcoxon signed-rank test with Bonferroni correction at 1 week and 1, 3, and 6 months, P = 0.15, P = 0.08, P = 0.016, P = 0.016, resp.; Figure 2A), although the values of DiffL-R amplitude did not reach statistical significance at any assessment time after surgery (Friedman test, χ2 = 8.0; df = 4; P = 0.09; Figure 2B). Figure 3A-B shows a trajectory of both eye positions for patient 1, with intermittent exotropia before and after surgery. Although the smooth pursuit for the patient initially showed good binocular coordination, disconjugacy of pursuit was revealed midway during smooth pursuit due to expression of exotropia (Figure 3A, small arrows). Because the patient remained orthophoric during smooth pursuit after surgery, binocular coordination of smooth pursuit was improved; however, his binocular coordination of catch-up saccades during smooth pursuit was fine even before surgery. Patient 2 consistently had good control of the exodeviation at near before and after surgery. Her binocular coordination of smooth pursuit was good during the pursuit examination before surgery (Figure 3C). After surgery, her good binocular coordination of smooth pursuit was maintained and her pursuit eye movement was smoother than before surgery because of a decreasing number of large catch-up saccades (Figure 3D). Patient 9 had constant exotropia at near and distance before surgery but good control of the exodeviation after surgery. Before surgery, there was a marked difference in
pursuit amplitude between both eyes, because she fixed her left eye to the target and her right eye deviated outward (Figure 3E,F). Relationships between Smooth Pursuit and Ocular Alignment The correlations between ocular deviation and DiffL-R amplitude and DiffL-R gain were significant (ocular deviation vs DiffL-R amplitude, ρ = 0.47 and P < 0.05; ocular deviation vs DiffL-R gain, ρ = 0.6 and P < 0.05). See Figure 4A,B. There were no correlations between preand postoperative changes in the amount of ocular deviation and pre- and postoperative changes in DiffL-R amplitude or those in DiffL-R gain (DiffL-R amplitude versus ocular deviation, ρ = 0.046 and P = 0.86; DiffL-R gain vs ocular deviation, ρ = −0.311 and P = 0.21). Discussion In our patient cohort, the DiffL-R gain and DiffL-R amplitude were significantly decreased after strabismus surgery; that is, the binocular coordination of smooth pursuit improved postoperatively. Moreover, the improvement tended to persist for at least 6 months. Some aspects of the surgical outcomes, including changes in ocular deviation and binocular visual function, may be involved in this improvement. As a result of the postoperative improvement in deviation angle, which leads to a mechanically balanced position of the left and right eyes, binocular coordination of smooth pursuit (ie, DiffL-R gain and DiffL-R amplitude) seems to be improved. The value of the DiffL-R gain and DiffL-R amplitude, which are decreased immediately after surgery, should increase as the deviation angle returns to the preoperative level. It is known that intermittent exotropia in humans recurs frequently in the long term after strabismus surgery.11,12 Consistent with this, in many of our patients, the ocular deviation angle more or less reverted toward the presurgical level during the 6 months after surgery, while the improvement in binocular coordination of
smooth pursuit tended to persist during this period. Therefore, the improvement of deviation angle may be less important for maintaining binocular coordination of smooth pursuit in the long term. We hypothesize that binocular coordination of smooth pursuit is determined by the patient’s ability to maintain heterophoria and binocular vision during examination of smooth pursuit. Pullela and colleagues5 reported that the changes in smooth pursuit gain noted immediately after surgery returned to preoperative levels by 6 months after surgery in monkeys with exotropia. Their experiment used 2 monkeys that had no binocular vision function because of artificial exotropia induced by prism goggles in infancy (the sensitive period of binocular vision development). In contrast, in the present study, most patients showed an increased ability to maintain periods of orthophoria after surgery. This indicates, in agreement with the findings of Lions and colleagues,2 that the maintenance of orthophoria during smooth pursuit and improvement in binocular vision function could influence the improvement in binocular coordination of smooth pursuit. Although the exodeviation angle reverted postoperatively over the long term, the maintenance of orthophoria during smooth pursuit and normal binocular vision could lead to continued improvement in binocular coordination of smooth pursuit. To support this hypothesis, cases of infantile exotropia (or infantile esotropia) without normal binocular vision must be compared before and after strabismus surgery. In the present study, DiffL-R amplitude and DiffL-R gain were correlated with the ocular deviation angle. The DiffL-R amplitude and DiffL-R gain were proportional to the exodeviation angle measured by alternate prism cover testing, when some patients showed exotropia during examination of smooth pursuit (see Figure 3A [patient 1], E [patient 9]). However, the DiffL-R amplitude and DiffL-R gain were small when the patient showed orthophoria during examination
of smooth pursuit, as seen in patient 2 (Figure 3C), even if the patient showed a large exodeviation. It is likely that a large deviation angle made it difficult to maintain orthophoria during smooth pursuit, as in patient 1 (Figure 3A). Therefore, it is likely that the DiffL-R amplitude and DiffL-R gain are correlated with the ocular deviation angle indirectly via the duration of orthophoria. The changes in DiffL-R amplitude and DiffL-R gain achieved by strabismus surgery were not correlated with the extent of improvement in deviation angle. These outcomes might be attributable to the influence of the data from patients with good binocular vision function despite large ocular deviation angles before surgery (patients 3 and 8). The values of the DiffL-R amplitude and DiffL-R gain before surgery were small in these patients, that is, binocular coordination in smooth pursuit was good, because they maintained orthophoria during smooth pursuit. Therefore, the changes in DiffL-R amplitude and DiffL-R gain achieved by surgery may not have been proportional to the extent of improvement in deviation angle. Furthermore, the small number of data on the change in DiffL-R amplitude and DiffL-R gain before and after surgery (ie, before vs 6 months after surgery) may have weakened the statistical power of the study to detect a significant correlation. Studies that include these examinations in a larger number of subjects will be needed to obtain solid evidence on this correlation. The limitations of this study include the wide range of patient ages and the small number of cases. Furthermore, the patients included had varying ocular deviation angles. Therefore, our conclusions are offered with caution. Moreover, the relationship between the change in smooth pursuit after surgery and the changes in ocular deviation angle and binocular vision function after surgery must be monitored for more than 6 months to determine whether or not improvement of binocular coordination persists.
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Legends FIG 1. Binocular alignment at near (A) and distance (B) for each patient. Solid lines indicate each individual; mean for all patients is indicated by the dashed line with solid circles. The time points are before surgery (Pre) and 1 week (1W), and 1, 3, and 6 months (1M, 3M, 6M) after surgery. FIG 2. Comparison of differences in gain (A) and amplitude (B) between eyes. The white box indicates the preoperative difference. The shaded box indicates the difference at 1 week postoperatively; the gray box, at 1 month; the dotted box, at 3 months; and the light gray box, at 6 months. Horizontal black lines within each box indicate median values. Boxes extend from the 25th to the 75th percentile of each period; upper and lower lines indicate maximum and minimum values. The differences in gain and amplitude between eyes were significantly improved at all assessment times after surgery. *P < 0.05. FIG 3. Typical examples (patients 1, 2, 9) of smooth pursuit for the right eye (solid light gray line) and left eye (solid gray line) waveform. Eye position during smooth pursuit before surgery (patients 1 [A], 2 [C], and 9 [E]) and 1 month after surgery (patients 1 [B], 2 [D], and 9 [F]). Patient 1 had weak orthophoria that switched to exotropia while tracking the target without covering one eye before surgery. Patient 2 had good control of the exodeviation at near before and after surgery. Patient 9 had constant exotropia at near and distance before surgery, although she could have good control of the exodeviation after surgery. The small arrow indicates the beginning of the time that disconjugacy of pursuit was evident. FIG 4. A, Relationship between difference in gain and ocular deviation, showing a correlation. B, Relationship between difference in amplitude and ocular deviation, also showing a correlation.
Table 1. Summary of patients with exotropia No. Age, Sex years 1 2 3 4 5 6 7 8 9
12 12 29 10 10 31 12 39 45
M F F F M F F F F
Surgery, mm
LE MR 6.5, LR 6.5 BE LR 5.0 RE MR 5.5, LR 5.5 RE MR 6.5, LR 6.5 RE MR 6.5, LR 6.0 LE MR 6.5, LR 8.0 LE MR 5.0, LR 4.5 RE MR 7.0, LR 8.0 RE MR 8.0, LR 9.0
Deviation at near, PDa Pre 40 18 80 45 30 86 25 113 95
1W 6 4 16 −1 −14 6 0 18 18
6M 20 6 10 8 2 20 12 57 35
Deviation at distance, a PD Pre 1W 6M 40 8 16 35 2 4 60 6 6 45 −1 4 30 −10 2 63 2 20 25 -2 6 72 12 50 80 −1 25
Convergence
Stereopsis, arcsec Fusion range, deg Before After Before After Pre Good Good 40 40 −15 to +10 Good Good 40 40 −13 to +40 Good Good 80 40 −15 to +22 Good Good 140 40 — Poor Good 40 40 −2 to +9 Good Good 3000 100 — Good Good 140 50 — Good Good 50 40 −25 to +30 Poor Good >3000 400 —
BE, both eyes; LE, left eye; LR, lateral rectus; MR, medial rectus muscle; RE, right eye muscle; PD, prism diopter. a
Pre-, before surgery; 1W, 1 week after surgery; 6M, 6 months after surgery.