Spinocerebellar ataxias (SCAs) represent a group of autosomal dominant disorders that are clinically, pathologically, and genetically heterogeneous.1 Irreversible and progressive cerebellar and extracerebellar neurodegeneration may induce the complex clinical manifestations of the SCAs.1,2 Patients with SCAs frequently develop various ocular motility abnormalities, including diplopia, gaze-evoked nystagmus, abnormal pursuit, hypermetric or hypometric saccades, and ophthalmoparesis.1,2 The incidence of diplopia is higher in patients with SCA type 3 than in patients with other SCA types.1,2 As such, diplopia may be a characteristic feature of SCA type 3, and impairments in divergence without ocular movement limitation may cause the diplopia.2,3
Although clinical evaluations of eye movements in SCAs have been well documented, there are no specific guidelines for strabismus surgery in patients with SCAs. Therefore, the purpose of this study was to evaluate surgical responses and outcomes of bilateral medial rectus (BMR) recession in esotropic patients with SCAs. The results were compared with those from a control group consisting of esotropic patients without neurologic disorders, and factors influencing the surgical responses were evaluated.
Patients and Methods
This study was approved by the instutional review board of Massachusetts Eye and Ear Infirmary, Harvard Medical School. The medical records of patients with SCAs and acquired esotropia who underwent strabismus surgery between July 2006 and May 2015 were reviewed retrospectively. SCAs were diagnosed based on clinical symptoms and findings, and all SCA cases were confirmed by genetic analysis. Patients were included if BMR recession was performed to correct their esotropia in the primary position. Patients with acquired esotropia matched for age and deviation angle and without neurologic disorders who underwent BMR recession were also included in this study and served as the control group. Patients with a history of previous strabismus surgery, concomitant ophthalmological problems, simultaneous vertical rectus muscle surgery, or oblique muscle surgery, as well as those with a postoperative follow-up duration of less than 3 months, were excluded. Informed consent was obtained from all patients prior to their strabismus surgery.
Alternate prism cover testing with accommodative targets for fixation at 1/3 and 6 m was performed. Data collection included age at surgery, sex, follow-up duration, preoperative and postoperative deviation measurements, and the amount of surgical recession performed.
Surgery was based on the largest angle of deviation measured at distance (Table 1). The suture material used in the BMR recession was absorbable polyglactin 910 (Vicryl; Ethicon, Somerville, NJ). Postoperative horizontal deviation angles in the primary position at distance and near were measured at 1 week and 3 months postoperatively. Surgical success was defined as having less than 8 prism diopters (PD) of horizontal deviation or less at distance in the primary position at the last follow-up. Undercorrection was defined as esotropia of 8 PD or greater, and overcorrection was defined as consecutive exotropia of 8 PD or greater. The surgical response was defined as the amount of corrected esodeviation divided by the amount of BMR recession (PD/mm). The distance-near disparity was defined as the difference between the deviation at distance and near. Postoperative outcome measurements included surgical success rates, surgical responses, and the distance-near disparity based on the postoperative alignment at the initial and the last follow-up examinations, which were analyzed and compared between the two groups.
BMR Recession in Esotropic Patients With SCA and Esotropic Controls Without Neurologic Disorders
Statistical analyses were performed with SPSS software (version 18.0; SPSS, Inc., Chicago, IL). The Wilcoxon signed-rank test was used to compare preoperative and postoperative data. The Mann–Whitney U and Fisher's exact tests were used to compare the data between the two groups. P values of less than .05 were considered statistically significant.
The study included 5 patients with SCAs and esotropia and 10 esotropic controls without neurological disorders. All patients with SCAs had SCA type 3, which was genetically confirmed by the presence of a mutation in the ataxin-3 gene. These patients did not show abduction deficits or slow saccades, which was correlated with higher disease severity and involved at a later stage of disease.1 In the control group, 4 patients were diagnosed as having age-related distance esotropia, and 6 patients were diagnosed as having adult-onset esotropia. The latter subgroup had esotropia greater at distance but did not meet the diagnostic criteria of age-related distance esotropia.
During surgery, none of patients in this study demonstrated an abnormally tight or loose medial rectus muscle by forced duction test. No patients with SCA and esotropia showed any extraocular muscle to be atrophic on magnetic resonance imaging.
The preoperative demographics including mean preoperative esodeviation at distance (20 vs 17.3 PD, P = .214) were not significantly different between esotropic patients with SCAs (SCA group) and esotropic patients without neurologic disorders (control group) (Table 2). Table 3 shows the mean preoperative and postoperative deviation angles measured at distance in the primary position over time. The SCA group showed significant undercorrection compared with the control group on postoperative week 1 (4.8 vs 1.0 PD, P = .048) and at the final follow-up (6.8 vs 1.8 PD, P = .032). The mean amount of corrected esotropia in the primary position was 13.6 PD in the SCA group and 15.5 PD in the control group (P = .348).
Mean Preoperative and Postoperative Esodeviation at Distance in Primary Position
Surgical success was defined as having less than 8 PD of horizontal deviation at distance in the primary position at the last follow-up visit. The surgical success rate for the SCA group was 40% and that for the control group was 80% (P = .095). In the SCA group, 60% of patients were undercorrected and none of the patients were overcorrected. In the control group, 20% of patients were undercorrected and none of the patients were overcorrected.
Table 4 shows the surgical responses of BMR recession and the amount of preoperative and postoperative (at the last follow-up visit) distance-near disparity for each group. The surgical response was defined as the amount of corrected esodeviation divided by the amount of BMR recession (PD/mm). The SCA group demonstrated a significantly reduced surgical response compared with the control group (3.15 vs 3.87 PD/mm, P = .004). In addition, significant differences in the surgical response were noted between patients in whom surgical success was achieved and those with postoperative undercorrection in the SCA group (6.0 vs 1.3 PD/mm, P < .001) and in the control group (4.2 vs 2.8 PD/mm, P < .001). There was no statistically meaningful difference in the mean amount of preoperative distance-near disparity between the SCA group and control group (6.2 vs 4.4 PD, P = .291). However, there was a significant difference in the mean amount of postoperative distance-near disparity between the SCA and control groups (8.0 vs 1.1 PD, P = .001). In the SCA group, the amount of distance-near disparity slightly increased from before to after BMR recession, although the difference was not statistically significant (6.2 vs 8.0 PD, P = .346).
Surgical Response and Amount of Preoperative and Postoperative Distance-Near Disparity at the Last Follow-up
This study found that esotropic patients with SCA type 3 demonstrated significant undercorrection following BMR recession when compared with the results of normal controls. Despite the lack of statistical significance (P = .095), the surgical success rate (40%) of esotropic patients with SCA type 3 was much lower than the success rate (80%) of normal controls. This difference may be due to a significantly lower surgical response of BMR recession (3.15 vs 3.87 PD/mm, P = .004), and greater amount of postoperative distance-near disparity (8.0 vs 1.1 PD, P = .001) in esotropic patients with SCA type 3 than in normal controls.
Our results are consistent with those of Hüfner et al.,4 who reported that cerebellar dysfunction was associated with esotropia/esophoria at distance in adulthood. Specifically, they found that patients with cerebellar dysfunction had a frequency of esotropia/esophoria at distance that was 13.3 times higher than those of patients without cerebellar dysfunction.4 Further, Ohyagi et al.2 reported that esotropia and diplopia with impairment of vergence movements but without ophthalmoplegia were observed in 5 patients with SCA type 3.
Clinical observations support that the cerebellum plays an important role in vergence eye movements.4,5 The cerebellar flocculus contains neurons that discharge with divergence.4–6 The oculomotor vermis, caudal fastigial nuclei, and posterior interposed nuclei of the cerebellum are also involved in vergence.4,5 In animal experiments, activation of the caudal fastigial nuclei by damaged oculomotor vermis or inactivation of the posterior interposed nuclei leads to esotropia.4,7,8 Therefore, it has been proposed that convergence is controlled by the oculomotor vermis–caudal fastigial nuclei pathway and divergence is controlled by the oculomotor vermis–posterior interposed nuclei flocculus pathway.4,5,9–11 Moreover, divergence-related neurons in the oculomotor vermis are more susceptible to injury, whereas convergence may have better compensatory mechanisms.5,12 As such, dysfunction of the oculomotor vermis, the flocculus, or both leads to esotropia greater at distance in patients with SCA type 3.4,5 Therefore, an increased esotonus of the eyes, reduced divergence with normal convergence, or both may be a pathophysiologic mechanism underlying the significant undercorrection that we observed following BMR recession in esotropic patients with SCA type 3 compared with controls.
One interesting finding of our study was the greater amount of postoperative distance-near disparity in esotropic patients with SCA type 3 than normal controls. We also noticed that the amount of distance-near disparity slightly increased after BMR recession in patients with SCA type 3. We speculate that the reason for this finding may be related to significantly reduced horizontal phoria adaptation in patients with cerebellar lesions.4,13 Alternatively, the increased amount of postoperative distance-near disparity in patients with SCA may be another manifestation of SCA disease activity progression. Unfortunately, fusional abilities were not measured in this study.
Our findings suggest that important components for achieving surgical success in esotropic patients with SCA type 3 are increasing the surgical response of BMR recession and decreasing the amount of distance-near disparity. Reduced divergence with normal convergence in those patients will produce postoperative esodrift after strabismus surgery. In the current study, the mean postoperative esodrift was 6.8 PD at 3 months postoperatively. Therefore, we suggest changing the recommendation for patients with SCA type 3 undergoing BMR recession for an overcorrection of at least 7 PD to compensate for possible postoperative esodrift. We also recommend performing BMR recession with a slanting procedure14: recessing the lower poles of the medial rectus muscle more than the upper poles, which can reduce the distance-near disparity in patients with cerebellar dysfunction.
This study is somewhat limited by the small number of patients, mainly due to the extremely rare prevalence of SCA type 3, and by the relatively short follow-up time, which was approximately 4 months. Because this was a retrospective study, we could not measure other factors that may have influenced the surgical response, such as the presence of stereopsis or fusional abilities.
To the best of our knowledge, the current study is the first to access the surgical responses and outcomes following BMR recession in esotropic patients with SCA type 3. We observed a significant undercorrection due to postoperative esodrift after BMR recession in those patients. Accordingly, we recommend a slight overcorrection of 5 to 10 PD or adding a slanting procedure, as stated above, in planning strabismus surgery for this distinct group of patients.
- Moscovich M, Okun MS, Favilla C, et al. Clinical evaluation of eye movements in spinocerebellar ataxias: a prospective multi-center study. J Neuroophthalmol. 2015;35:16–21. doi:10.1097/WNO.0000000000000167 [CrossRef]
- Ohyagi Y, Yamada T, Okayama A, et al. Vergence disorders in patients with spinocerebellar ataxia 3/Machado-Joseph disease: a synoptophore study. J Neurol Sci. 2000;173:120–123. doi:10.1016/S0022-510X(99)00309-3 [CrossRef]
- Kirkham TH, Bird AG, Sanders MD. Divergence paralysis with raised intracranial pressure: an electro-oculographic study. Br J Ophthalmol. 1972;56:776–782. doi:10.1136/bjo.56.10.776 [CrossRef]
- Hüfner K, Frenzel C, Kremmyda O, et al. Esophoria or esotropia in adulthood: a sign of cerebellar dysfunction?J Neurol. 2015;262:585–592. doi:10.1007/s00415-014-7614-2 [CrossRef]
- Beh SC, Frohman TC, Frohman EM. Cerebellar control of eye movements. J Neuroophthalmol. 2017;37:87–98. doi:10.1097/WNO.0000000000000456 [CrossRef]
- Miles FA, Fuller JH, Braitman DJ, Dow BM. Long-term adaptive changes in primate vestibulovular reflex, III: electrophysiological observations in flocculus of normal monkeys. J Neurophysiol. 1980;43:1437–1476. doi:10.1152/jn.1918.104.22.1687 [CrossRef]
- Umetani T. Efferent projections from the flocculus in the albino rat as revealed by an autoradiographic orthograde tracing method. Brain Res. 1992;586:91–103. doi:10.1016/0006-8993(92)91376-P [CrossRef]
- Yamada J, Noda H. Afferent and efferent connections of the oculomotor cerebellar vermis in the macaque monkey. J Comp Neurol. 1987;265:224–241. doi:10.1002/cne.902650207 [CrossRef]
- Nitta T, Akao T, Kurkin S, Fukushima K. Vergence eye movement signals in the cerebellar dorsal vermis. Prog Brain Res. 2008;171:173–176. doi:10.1016/S0079-6123(08)00623-7 [CrossRef]
- Nitta T, Akao T, Kurkin S, Fukushima K. Involvement of the cerebellar dorsal vermis in vergence eye movements in monkeys. Cereb Cortex. 2008;18;1042–1057. doi:10.1093/cercor/bhm143 [CrossRef]
- Gamlin PD. Neural mechanisms for the control of vergence eye movements. Ann N Y Acad Sci. 2002:956:264–272. doi:10.1111/j.1749-6632.2002.tb02825.x [CrossRef]
- Sander T, Sprenger A, Neumann G, et al. Vergence deficits in patients with cerebellar lesions. Brain. 2009;132:103–115. doi:10.1093/brain/awn306 [CrossRef]
- Milder DG, Reinecke RD. Phoria adaptation to prisms: a cerebellar-dependent response. Arch Neurol. 1983;40:339–342. doi:10.1001/archneur.1983.04050060039005 [CrossRef]
- Snir M, Axer-Siegel R, Shalev B, Sherf I, Yassur Y. Slanted lateral rectus recession for exotropia with convergence weakness. Ophthalmology. 1999;106:992–996. doi:10.1016/S0161-6420(99)00522-9 [CrossRef]
BMR Recession in Esotropic Patients With SCA and Esotropic Controls Without Neurologic Disordersa
|Deviation Angle of Esotropia (PD)||Amount of BMR Recession (mm)|
|Characteristic||SCA Group||Control Group||Pa|
|No. of patients||5||10||–|
|Mean age at surgery (y)||56.6 (43 to 75)||56.4 (43 to 75)||.490|
|Preoperative esotropia in primary position (PD)|
| At distance (mean, range)||20.0 (11 to 28)||17.3 (11 to 28)||.214|
| At near (mean, range)||13.8 (2 to 22)||12.9 (6 to 26)||.407|
| Amount of BMR recession||4.1 ± 1.1||4.0 ± 0.8||.382|
Mean Preoperative and Postoperative Esodeviation at Distance in Primary Positiona
|Variable||SCA Group||Control Group||Pb|
|Preoperative||20.0 ± 7.0||17.3 ± 6.0||.214|
|Postoperative 1 week||4.8 ± 3.9||1.0 ± 4.2||.048|
|Postoperative 3 months||6.8 ± 6.9||.032|
|Mean amount of corrected esotropia||13.6 ± 11.8||15.5 ± 6.8||.348|
Surgical Response and Amount of Preoperative and Postoperative Distance-Near Disparity at the Last Follow-upa
|Characteristic||Surgical Response (PD/mm)||Preoperative Distance-Near Disparity||Postoperative Distance-Near Disparity|
|SCA group||3.15||6.2 ± 1.6||8.0 ± 5.1|
| Surgical success (n = 2)||5.97|
| Undercorrection (n = 3)||1.28|
|Control groupc||3.87||4.4 ± 6.9||1.1 ± 2.1|
| Surgical success (n = 8)||4.16|
| Undercorrection (n = 2)||2.75|