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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 2  |  Issue : 4  |  Page : 140-143

Botulinum injection for the treatment of acute esotropia resulting from complete acute abducens nerve palsy☆


1 Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou; Department of Medicine, Chang Gung University, Taiwan, ROC
2 Department of Medicine, Chang Gung University, Taiwan, ROC

Date of Web Publication7-Dec-2012

Correspondence Address:
Ling Yuh Kao
Department of Ophthalmology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan
ROC
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Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.tjo.2012.07.005

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  Abstract 


Purpose: The objective of this study was to investigate the effectiveness of botulinum toxin A (BTX-A) injections in the treatment of acute esotropia resulting from complete acute abducens nerve palsy. Methods: Fifteen patients treated for complete acute abducens nerve palsy in our clinic were retrospectively reviewed. All patients who experienced an onset within 3 months and who were treated with early subtenon BTX-A injections at the ipsilateral medial rectus muscle without electromyography (EMG) guidance were included in this study. Responses and complications were recorded during a follow-up of at least 6 months.
Results: Thirteen patients who had trauma and two patients who had brain tumor that caused their abducens nerve palsy were enrolled. Overall, six patients (40%) had full recovery and two patients (13%) had partial recovery, but the residual esotropia could be tolerated with prism correction in an average of 14.6 weeks. Seven patients (47%) received strabismus surgery afterward. Patients who did not respond well to early BTX-A injections at the 1-week interval were prone to subsequent surgical intervention (p = 0.026). Three eyes (20%) had transient subconjunctival hemorrhage following the subtenon space injection; no other complications were found after the treatment.
Conclusion: BTX-A offers patients with complete abducens palsy a possible better chance to regain binocular vision and indicates whether additional surgical interventions are needed for these patients. We also discovered that the subtenon space injection of BTX-A without EMG guidance was a safe, time-saving, and simple technique.

Keywords: abducens nerve palsy, botulinum toxin A injection, sixth nerve palsy


How to cite this article:
Chen YH, Sun MH, Hsueh PY, Kao LY. Botulinum injection for the treatment of acute esotropia resulting from complete acute abducens nerve palsy☆. Taiwan J Ophthalmol 2012;2:140-3

How to cite this URL:
Chen YH, Sun MH, Hsueh PY, Kao LY. Botulinum injection for the treatment of acute esotropia resulting from complete acute abducens nerve palsy☆. Taiwan J Ophthalmol [serial online] 2012 [cited 2021 Mar 7];2:140-3. Available from: https://www.e-tjo.org/text.asp?2012/2/4/140/203734




  1. Introduction Top


The sixth nerve is vulnerable to injury with an estimated incidence of 11.3 in 100,000.[1] The causes of abducens nerve palsy include idiopathic disorder (29.6%), vascular disorder (17.7%), head trauma (16.7%), neoplasm (14.6%), aneurysm (3.6%), and other conditions (17.9%).[1] Previous studies discovered that the recoveryof abducens nerve palsy is associated with disease severity, etiology, baseline binocular function, and numerous uncontrollable factors.[1],[2],[3] The recovery rate is higher in patients with diabetes mellitus, hypertension, and vascular lesion. Poor prognostic factors include trauma or tumor-related diseases, bilaterality, complete palsy, or esotropia presented with more than 50 prism diopters (PDs).[1],[2],[4],[5],[6] However, the number of studies that focused on patients with poor outcomes is less.[5],[7],[8]

Botulinum toxin A (BTX-A) injection was approved by the Food and Drug Administration (FDA) in the United States in 1989 for treating strabismus.[1] Scott and Kraft[9],[10] have demonstrated that BTX-A treatment permits a more complete abduction resolution in patients with abducens nerve palsy by reducing the contracture of the ipsilateral medial rectus muscle. BTX-A injection has been used to treat various conditions, including chronic or acute phases, as well as cases with or without surgery.[10],[11],[12],[13],[14],[15],[16],[17],[18] BTX-A injection shortens the recovery, provides earlier binocularity, and reduces diplopia. However, some authors found no significant difference between treatment with BTX-A and natural recovery without treatment.[14] Effect of BTX-A injection remains inconclusive.

Complete abducens nerve palsy has a worse outcome than the incomplete type. Studies that strictly focus on complete palsy patients are less addressed; the effects of BTX-A on these patients remains to be investigated and the majority of studies have been performed on Caucasians. Therefore, we investigated the courses, outcomes, and complications of 15 complete acute abducens nerve palsy patients whom treated with subtenon injection of BTX-A within 3 months of onset to find out whether the patients have a possible better chance to regain binocular vision and whether they need additional surgical interventions.


  2. Methods Top


From March 1993 to February 2008, data for patients who sought treatment for diplopia resulting from abducens nerve palsy at our Neuro-Ophthalmology Clinic and who were treated with a subtenon space injection of BTX-A were retrospectively collected. The study was approved by the Institutional Review Board at Chang Gung Memorial Hospital, Taoyuan, Taiwan (99-0417B). Patients who experienced abducens nerve palsy with an onset within 3 months with a complete abduction deficit in one or both eyes, according to Scott and Kraft’s scale,[9],[10] and had a follow-up duration of at least 6 months were included in this study. Patients of vascular or idiopathic origin or with incomplete chart records and a follow-up duration of less than 1/2 year were excluded.

All patients underwent a complete ophthalmic examination, including a fundus examination; an ocular movement examination; a best-corrected visual acuity assessment; an assessment of the angle of deviation with the prism cover in PD measured by simultaneous prism and cover test in the primary position at a distance of 6 m, and an assessment of the degree of abduction deficit using a scale described by Scott and Kraft.[9],[10] Complete palsy was defined as an abduction deficit of −4 or −5. To meet the research objective, the palsy severity in bilateral palsy cases was analyzed using the abduction deficit of the worst eye. Demographic information of the patients, including age, gender, general health, family history, and previous ocular history, was recorded. Treatment courses, outcomes, and complications were also recorded. A functional cure was defined as the absence of diplopia in the primary position subjectively, along with a distance esotropia of less than 10 PD in the primary position. Improvement was defined as at least a 10 PD decrease in deviation deficit before and after the BTX-A injection. Complications including ptosis, subconjunctival hemorrhage, hypertropia, dry eye, epiphoria, ectropion, facial numbness, brow droop, and acute angle closure glaucoma were recorded.

BTX-A injection was administered within 3 months of disease onset as topical anesthetic eye drops with 0.5% proparacaine hydrochloride (Alcaine®, Alcon, Mississauga, CA, USA). Five units of purified BTX-A (BOTOX®, Allergan, Irvine, CA, USA) was injected into the overlying subtenon space of the ipsilateral medial rectus muscle approximately 10 mm from the nasal limbus using a 27-gauge needle and a 1-cc insulin syringe. No electromyography (EMG) guidance was used. The duration of the entire procedure was less than 3 minutes.[17] The effect of the BTX-A injection was evaluated 1 week after the injection. If no effect was observed according to the clinical presentation of patients, additional BTX-A injections were scheduled.

Fisher’s exact test was used to analyze the categorical data. Statistical analyses were performed using the SPSS software package (Version 12.0 for Windows, SPSS Inc., Chicago, IL, USA). A two-tailed p value of 0.05 or less was considered significant for all tests.


  3. Results Top


Fifteen patients, eight males (53%) and seven females (47%), were enrolled in this study. Thirteen patients had trauma and two had tumors that caused their abducens palsy and manifested acute esotropia [Figure 1]. The conditions before and after BTX-A treatment by injection are listed in [Table 1]. One of the patients had bilateral involvement. The mean age of these patients was 40.5 years (range 11 -58 years). The mean follow-up duration was 16 months (range 6-84 months). Average deviations were 38.5 ± 12.9 and 13.7 ± 11.8 PD prior to the treatment of BTX-A and at the last follow-up, respectively. The mean elapsed time from disease onset to BTX-A injection was 8.4 ± 4.3 weeks (range 1–12 weeks). The mean period from the last injection to a stable result was 14.6 ± 13.3 weeks (range 1–42 weeks). The average dose of the BTX-A injection was 10.3 ± 6.7 units. The results are shown in [Table 1].
Table 1: Conditions before and after BTX-A injection.

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Figure 1: Cause of abducens palsy in all patients.

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Recovery conditions of the patients are given in [Table 2]. Nine patients (60%) received single injection of BTX-A. Among these patients, three had full recovery at a 6-month follow-up period, one had partial recovery with no need of surgical intervention, and five received subsequent surgical intervention. Six patients (40%) received an additional BTX-A injection. The average interval between the first and second injections was 3.7 weeks (range 1–8 weeks). Among these six patients, three had full recovery at a 6-month follow-up period, one had partial recovery with no need of surgical intervention, and two received strabismus surgery afterward.
Table 2: Recovery condition of the patients.

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Overall, six patients (40%) reached full recovery with final ocular alignment within 10 PD or no diplopia in the primary position, two patients (13%) had partial recovery but the residual esotropia could be tolerated with prism correction, and seven patients (47%) received strabismus surgery afterward (as shown in [Table 2]). Patients who did not respond well to early BTX-A injections at the 1-week evaluation did not show a lower chance of full recovery at 6 months (p = 0.089); however, they were more prone to receiving subsequent surgical intervention (p = 0.026) [Figure 2].
Figure 2: The association between the status following Botulinum toxin A (BTX-A) injection 1 week and the final recovery.

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During the follow-up examination of all the patients, complications caused by the BTX-A injections were evaluated. Only three eyes (20%) with transient subconjunctival hemorrhage were observed. There was no ptosis, vertical deviation, ectropion, facial numbness, brow droop, eyeball perforation, or acute angle closure glaucoma.


  4. Discussion Top


Treatment of abducens nerve palsy by using BTX-A injections with the aim of eliminating diplopia and eye movement limitation has been investigated, but the recovery rates vary broadly (37– 76%).[8],[13],[19],[20] Compared with the spontaneous recovery rate of nontreated patients (12–73%),[4],[5],[6],[21],[22] the BTX-A-treated patients had slightly improved prognosis. However, it is difficult to compare among studies because of their different designs, different number of patients enrolled, different severities of the disease, diverse underlying etiologies, variable duration from onset to BTX-A treatment, and different follow-up durations. The current study demonstrated that 40% of patients with acute-onset complete abducens palsy who underwent early BTX-A injection had full recovery [Table 2]. Poor response to BTX-A injection after a 1-week interval could indicate a possible need for surgical intervention in the future.

In the current study, 40% of the patients with acute esotropia related to complete sixth nerve palsy recovered completely after early treatment with BTX-A injection. The patients recruited in the current study had the most severe extent of disease and were doomed to have a poor prognosis as defined by Holmes et al,[2] who indicated that complete palsy or esotropia with more than 50 PD would have a poor prognosis. However, patients treated with BTX-A in our study seemed to have a better outcome than similar complete palsy patients who did not receive any treatment (35%).[4] Hung et al[8] even reported that 50% of patients with acute complete sixth nerve palsy recovered completely after BTX-A treatment. Because of the limitations of statistical analysis of these results, large-scale prospective studies with case-controlled designs may be needed in the future to confirm the effect of BTX-A treatment in patients with abducens nerve palsy.

The current study demonstrated an earlier recovery in an average of 14.6 weeks compared to 12–24 weeks reported in previous studies for spontaneous recovery.[4],[6] Although BTX-A injection did not show strong influence on the final recovery, the evaluation at 1 week post injection revealed that patients who responded poorly to the injection are likely to receive subsequent surgical intervention (p = 0.026). Daily lives of abducens palsy patients are disrupted by intolerable diplopia and compensatory head turns. Surgery is usually considered when the deviation has been stable for at least 6 months.[1] However, determination of the timing of surgical intervention for patients with poor recovery is more difficult during clinical judgments. Our study has provided a clue for determining whether additional surgical interventions are needed for these patients.

There are numerous ways of administering BTX-A.[7],[23],[24],[25] The commonest method is by EMG-guided injection through a topically anaesthetized conjunctiva, but complications ranging from conjunctival hemorrhage to more serious ones such as scleral perforation have been reported.[26] Lee et al[24] used an intramuscular BTX-A injection and discovered transient ptosis and vertical deviation in 24% of the patients. Scott and Kraft[9],[10] also reported the incidence of transient ptosis and temporary vertical tropia in 29.4% of 17 eyes when intramuscular injections were used. In this study, a subtenon injection method was employed. This method was published by Kao and Chao[1] in 2003, and no obvious complications were ever reported. Our study also found that only 20% of the patients had transient subconjunctival hemorrhage, but no other complications were found after this procedure. An animal model reported by Paik et al[25] illustrated that the effect and morphology between subtenon injection and intramuscular injection of BTX-A were equal at 4 weeks after injection. The subtenon injection of BTX-A without EMG guidance is a time-saving, simple, safe, and cost-effective technique in its clinical application.

Limitations of this study include small patient number, short follow-up duration, lack of conservatively treated patients for comparison, and retrospective design. However, the results offer clinicians a simple, effective, and safe choice for treating their abducens nerve palsy patients. The results also highlight the effectiveness of the BTX-A treatment.

In conclusion, BTX-A offers abducens palsy patients a possible better chance to regain binocular vision and clinicians a hint for determining whether additional surgical interventions are needed for these patients.



 
  References Top

1.
Goodwin D. Differential diagnosis and management of acquired sixth cranial nerve palsy. Optometry 2006;77:534–9.  Back to cited text no. 1
    
2.
Holmes JM, Beck RW, Kip KE, Droste PJ, Leske DA. Predictors of nonrecovery in acute traumatic sixth nerve palsy and paresis. Ophthalmology 2001;108:1457– 60.  Back to cited text no. 2
    
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8.
Hung HL, Kao LY, Sun MH. Botulinum toxin treatment for acute traumatic complete sixth nerve palsy. Eye (Lond) 2005;19:337–41.  Back to cited text no. 8
    
9.
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10.
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13.
Chuenkongkaew W, Dulayajinda D, Deetae R. Botulinum toxin treatment ofthe sixth nerve palsy: an experience of 5-year duration in Thailand. J Med Assoc Thai 2001;84:171–6.  Back to cited text no. 13
    
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Elston JS, Lee JP. Paralytic strabismus: the role of botulinum toxin. Br J Oph- thalmol 1985;69:891–6.  Back to cited text no. 15
    
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17.
Holmes JM, Beck RW, Kip KE, Droste PJ, Leske DA. Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. J AAPOS 2000;4:145–9.  Back to cited text no. 17
    
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Wagner RS, Frohman LP. Long-term results: botulinum for sixth nerve palsy. J Pediatr Ophthalmol Strabismus 1989;26:106–8.  Back to cited text no. 18
    
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Metz HS, Dickey CF. Treatment of unilateral acute sixth-nerve palsy with botulinum toxin. Am J Ophthalmol 1991;112:381–4.  Back to cited text no. 19
    
20.
Fitzsimons R, Lee JP, Elston J. Treatment of sixth nerve palsy in adults with combined botulinum toxin chemodenervation and surgery. Ophthalmology 1988;95:1535–42.  Back to cited text no. 20
    
21.
Rush JA, Younge BR. Paralysis of cranial nerves III, IV, and VI. Cause and prognosis in 1,000 cases. Arch Ophthalmol 1981;99:76–9.  Back to cited text no. 21
    
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Robertson DM, Hines JD, Rucker CW. Acquired sixth-nerve paresis in children. Arch Ophthalmol 1970;83:574–9.  Back to cited text no. 22
    
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Kowal L, Wong E, Yahalom C. Botulinum toxin in the treatment ofstrabismus. A review of its use and effects. Disabil Rehabil 2007;29:1823–31.  Back to cited text no. 23
    
24.
Lee J, Harris S, Cohen J, Cooper K, MacEwen C, Jones S. Results of a prospective randomized trial of botulinum toxin therapy in acute unilateral sixth nerve palsy. JPediatr Ophthalmol Strabismus 1994;31:283–6.  Back to cited text no. 24
    
25.
Paik HJ, Kang KD, Choi JS, Choi BG, Yim HB. Effects of botulinum A toxin injection on the extraocular muscle fiber layers: comparison between sub-tenon injection and intramuscular injection. Jpn JOphthalmol 2009;53:229–34.  Back to cited text no. 25
    
26.
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]


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