Efficacy of Botulinum Toxin Injection in Exotropia Treatment.

PURPOSE: Botulinum toxin (Botox) therapy is a well-known option for strabismus management and is often used in managing esotropia. Exotropia is also a common type of strabismus; however, the effectiveness of Botox in improving exotropia is still ambiguous. In this study, we report our experience in using Botox to manage the various types of exotropia.
METHODS: A retrospective cohort study was conducted at King Khaled Eye Specialist Hospital Riyadh, Saudi Arabia. Medical records of patients with exotropia who received Botox from 2014 to March 2020 were reviewed. The main success indicator was a remaining angle of less than 10 prism diopters (PD).
RESULTS: A total of 97 cases were reviewed, with 57 (58.8%) males and 40 (41.2%) females. The age ranged from 2 months to 40 years. The most prevalent diagnosis was sensory exotropia. Overall, 28 patients (28.9 %) and 49 patients (50.5%) achieved an angle of deviation within 10 PD and within 20 PD, respectively. Female patients had a better response to Botox than males, with 32.5% of them achieving an angle of deviation within 10 PD and 60% achieving an angle of deviation within 20 PD. We found that the change in the angle of deviation increased as the Botox dose was increased.
CONCLUSION: Botox represents a possible safe alternative to surgery in the management of some exotropia types. The success rate differs by type, with basic exotropia scoring the highest. The presence of poor vision and amblyopia leads to a significantly lower success rate. Copyright:

Introduction

Botulinum toxin (Botox) is a neurotoxin produced by Clostridium botulinum. Treatment of extraocular muscles with Botox was first reported in 1981.[1] Botox injection is a safe, effective, and noninvasive pharmacological alternative to surgery for strabismus, oculomotor paralysis, nystagmus, and other extraocular muscle dysfunctions, despite the transient side effects of ptosis and diplopia. Some types of strabismus respond better than others, for example, cases of concomitant strabismus with normal muscle elasticity accompanied by a functioning ipsilateral antagonist.[2]

The onset of action usually requires 24–72 h, peaking at approximately 10 days, and takes 2–3 months to fade away, depending on the patient's age, extraocular muscle contracture or elasticity degree, and strabismus type.[3] Once its effect ends, a permanent deviation correction is accomplished. According to Etezad Razavi et al.,[4] 66.7% of the exotropia patients achieved good fusional control ability, confirming the value of Botox for treatment. This study was aimed to evaluate the effect of lateral rectus muscle Botox injections in treating different exotropia types.

Methods

This was a retrospective cohort study. The study was approved by the Institutional Research Board (IRB) of KKESH (IRB no 2067-R) and the requirement for informed consent was waived due to the retrospective nature of the study.

All patients who received Botox injection for exotropia at the King Khaled Eye Specialist Hospital from January 2014 to March 2020 were considered for this study. The exclusion criteria were (1) previous Botox injections outside our hospital or (2) previous orbital decompression surgery.

The patients' file review included extracting detailed history of strabismus, previous treatments, complete ophthalmologic and orthoptic assessment including visual acuity, extraocular muscle function assessment, angle of deviation, final diagnosis, and treatment options offered.

Procedure

After appropriate preoperative diagnostic assessment, all patients were taken to the operating room, inhalational anesthesia was administered, and the injection site was chosen according to the standard anatomical site of the target muscle. The detailed characteristics of the study population are presented in Table 1.

Table 1

Baseline characteristics of the study population (n=97)

Characteristics	Frequency, n (%)
Age (year), median (IQR)	13.03 (18.01)
Sex
Male	57 (58.8)
Female	40 (41.2)
Previous surgery
No	45 (46.4)
Yes	52 (53.6)
Type of exotropia
Sensory	30 (30.9)
Consecutive	24 (24.7)
Basic	21 (21.6)
Intermittent	15 (15.5)
Other	7 (7.2)
Previous Botox treatment
No	88 (90.7)
Yes	9 (9.3)
Systemic disease
None	84 (86.6)
Yes	13 (13.4)

IQR: Interquartile range, Botox: Botulinum toxin

The Botox dose varied according to the surgeon's preference (5–25 IU) per muscle. All patients were followed up at least twice, between 2 and 16 months after the injection. During each visit, the deviation of the eye was documented as esotropia, exotropia, or orthophoria.

The primary measure of success was the residual angle of horizontal strabismus at the last visit, which allows for the development of binocularity in pediatric patients or cosmetically acceptable management in adults. A residual angle of 10 prism diopters (PD) or less is generally considered an acceptable outcome and was used as such in our study. Thus, horizontal deviation or a remaining angle of more than 10 PD at the last post injection visit was considered a failure indicator.

Statistical analysis

Data were entered using Microsoft Access 2010 (Microsoft Corporation, Redmond, Washington) and analyzed using STATA 16.0 (StataCorp LLC, College Station, TX, USA). Continuous data were presented as means with standard deviation/medians with interquartile range (IQR). Categorical data were presented as frequencies and percentages. An exploratory data analysis was undertaken to visualize trends in the data. A scatterplot of change in the angle of deviation versus Botox dose was plotted. A locally weighted smoothing (LOWESS) curve and a linear fit were applied to the data to visualize the relationship between the angle of deviation and Botox dose. The overall and subgroup incidence of achieving an angle of deviation within 10 PD and 20 PD after a single botulinum toxin injection were evaluated. Factors associated with achieving an angle of deviation within 20 PD were examined using Log-binomial regression analysis. A P value < 0.05 was considered statistically significant.

Results

Of the 100 cases reviewed, three were excluded based on the exclusion criteria. The final sample was 97, with 57 (58.8%) males and 40 (41.2%) females [Figure 1].

Figure 1

The sex of patients in our study

The participants' age ranged from 2 months to 40 years, with a median (interquartile range) of 13.03 (18.01) years. The most prevalent diagnosis was sensory exotropia, followed by consecutive exotropia [Figure 2].

Figure 2

Distribution of types of exotropia in our study

Of the participants, 86.6% had no systemic disease and 46.4% had no previous surgery. Overall, 28 patients (28.9 %) and 49 patients (50.5%) achieved an angle of deviation within 10 PD and within 20 PD, respectively. Female patients had a better response to Botox than males, with 32.5% of them achieving an angle of deviation within 10 PD and 60% achieving an angle of deviation within 20 PD. We found that the change in the angle of deviation increased as the Botox dose was increased [Table 3 and Figure 3]. Namely, lower doses were less successful in achieving improvement in the degree of exotropia; high dosages were more effective at lowering the PD and correcting the strabismus.

Table 2

Frequency of patients achieving an angle of deviation within 10 prism diopters and 20 prism diopters after a single botulinum toxin injection

Characteristic	n	Achieving angle of deviation within 10 PD, frequency (number of patients), n (%)	Achieving angle of deviation within 20 PD, frequency (number of patients), n (%)
Sex
Male	57	15 (26.3)	25 (43.9)
Female	40	13 (32.5)	24 (60.0)
All	97	28 (28.9)	49 (50.5)
Type of exotropia
Sensory	30	2 (6.7)	6 (20.0)
Consecutive	24	6 (25.0)	14 (58.3)
Basic	21	11 (52.4)	15 (71.4)
Intermittent	15	5 (33.3)	8 (53.3)
Other	7	4 (57.1)	6 (85.7)
Previous surgery
No	45	17 (37.8)	28 (62.2)
Yes	52	11 (21.2)	21 (40.4)
Previous Botox treatment
No	88	26 (29.5)	45 (51.1)
Yes	9	2 (22.2)	4 (44.4)
Systemic disease
None	84	25 (29.8)	44 (52.4)
Yes	13	3 (23.1)	5 (38.5)
Botox dose (units)
<20	54	9 (16.7)	23 (42.6)
≥20	43	19 (44.2)	26 (60.5)

Botox: Botulinum toxin

Table 3

Log-binomial regression analysis of the relationship between achieving an angle of deviation within 20 prism diopters and Botulinum toxin dose

	Crude analysis				Multivariable analysis
	Incidence ratio	LCI	UCI	P	Incidence ratio	LCI	UCI	P
Age (years)	0.99	0.98	1.01	0.405	1.02	1.0001	1.03	0.049
Sex
Malea				0.115				0.059
Female	1.37	0.93	2.02		1.41	0.99	2.00
Type of exotropia
Sensorya
Consecutive	2.92	1.32	6.46	0.008	3.96	1.81	8.67	0.001
Basic	3.57	1.66	7.71	0.001	3.02	1.24	7.34	0.015
Intermittent	2.67	1.13	6.32	0.026	2.87	1.09	7.53	0.032
Other	4.29	1.96	9.36	<0.001	3.86	1.68	8.89	0.001
Previous surgery
No	1.54	1.03	2.31	0.036	1.54	0.75	3.16	0.234
Yesa
Previous Botox
No	1.15	0.54	2.47	0.718	1.16	0.49	2.72	0.738
Yesa
Systemic disease
None	1.36	0.66	2.80	0.401	1.30	0.65	2.59	0.457
Yesa
Botox dose (units)	1.01	1.001	1.03	0.028	1.01	0.996	1.03	0.138

aThis parameter is not shown. LCI: Lower confidence interval, UCI: Upper confidence interval, Botox: Botulinum toxin

Figure 3

Scatterplot of the angle of deviation change as a function of botulinum toxin (Botox) dose assessed at the follow-up visits. The circles denote the degree of correction in the angle of deviation of each patient. Botox dose is cumulative. Locally weighted scatterplot smoothing (Lowess, Blue) and linear fit (Cranberry) to the data are shown

Discussion

This study analyzed the success rate of Botox injection in the treatment of exotropia. The most prevalent diagnosis was sensory exotropia, comprising 30.9% of the strabismus cases included in our study. No large-scale studies were found in the literature with a comparable prevalence.

The injection dose in our study ranged from 5 to 25 IU per muscle, following the surgeons' preference and experience. Furthermore, a literature search revealed no clear guidelines for Botox doses to treat strabismus, according to neither the angle of deviation nor the type of strabismus. However, the doses in our study were similar to those used in other studies. For example, Merino et al. used doses of 2.5–22.5 IU per muscle.[5]

The overall success rate (a correction within 10 PD) was 28.9%. Females had a better response to the treatment than males. Basic exotropia scoring the highest (52.4% achieving angle of deviation within 10 PD) and the lower rate of improvement in alignment was found in sensory exotropia (only 20% improvement to < 20 PD) or patients with significant amblyopia.

There were no severe complications observed, such as perforation of the globe or endophthalmitis, during the early (1-month) or late (6-month) postinjection follow-up visits. Ptosis and esotropia were considered desired outcomes in the first postinjection visit since their presence implied a positive injection effect. These have almost been resolved by the second postinjection visit. Furthermore, no complications associated with anesthesia were documented. This might be attributed to the use of mask anesthesia instead of the more traumatizing endotracheal intubation used with the general anesthesia performed in all pediatric strabismus surgeries. Furthermore, mask anesthesia helps avoid the decrease in cognitive functions related to general anesthesia when it is applied in early childhood.

The retrospective nature of the study with some incomplete documentation of the sensory status of the patients near was a limitation.

Conclusion

Botox represents a safe and repeatable alternative to surgery in the management of different exotropia types. The success rate differs by type, with basic exotropia scoring the highest. The presence of poor vision and amblyopia leads to a significantly lower success rate. In our study, we could not find definitive factors affecting the success rate. Further large-scale prospective studies are needed to explore the effectiveness of Botox in certain exotropia types.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.