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Management of infantile esotropia

Hug, Denise

Current Opinion in Ophthalmology: July 2015 - Volume 26 - Issue 5 - p 371–374
doi: 10.1097/ICU.0000000000000190
PEDIATRICS AND STRABISMUS: Edited by Bruce M. Schnall
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Purpose of review Surgical treatment has been the accepted mode of treatment for infantile esotropia for decades. The present review of recent literature evaluates the current standing of: type of surgery performed and best timing of surgery to achieve optimal results.

Recent findings Recent studies suggest that early surgical intervention is of benefit by improving the probability of developing stereopsis. A significant advantage of the type of surgical intervention has yet to be demonstrated by the current studies. Botulinum toxin continues to be used for treatment of infantile esotropia, although it has not been shown to be a superior treatment.

Summary Although many theories exist, the true cause of infantile esotropia remains unknown. The literature suggests that treatment before age 2 and perhaps even earlier improves the potential for binocular vision. After significant review of literature, it is clear that surgery is the treatment of choice for infantile esotropia but no method has a clear advantage. Efforts to define the best surgical procedure and timing of surgery through prospective, randomized multicenter trials are warranted.

Children's Mercy Hospital, Associate Professor of Ophthalmology, University of Missouri – Kansas City, USA

Correspondence to Denise Hug, MD, 3101 Broadway, Kansas City, MO 64111, USA. Tel: +1 816 960 8030; e-mail: dhug@cmh.edu

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INTRODUCTION

Infantile esotropia is defined as the onset of constant crossing in children less than 6 months of age. There are several other clinical findings that often accompany infantile esotropia including: amplitude of the angle being greater than 30 prism diopters, dissociated vertical deviation, dissociated horizontal deviation, inferior oblique overaction, latent nystagmus, cross fixation with pseudoabduction deficit, low degree of hyperopia (less than 3 diopters), and amblyopia. The incidence of infantile esotropia is approximately 1% [1], making this an important issue for pediatric ophthalmologist.

Box 1

Box 1

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TREATMENT OF INFANTILE ESOTROPIA

The goal of treatment of infantile esotropia is to align the visual axes to promote the development of binocular vision. The mainstay of treatment is surgical intervention. The standard forms of surgical intervention are variable and include: bilateral medial rectus recession, unilateral recession/resection, bilateral medial rectus recession with resection of one lateral rectus, and bilateral recession/resection.

In addition, botulinum toxin has been used as a primary intervention, augmentation during primary surgery, and as treatment for small angle residual esotropia [2,3].

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Timing of treatment

The first issue to address is the timing of surgery. Despite evidence that disruption in the visual system early in life leads to poor binocularity, there still seems to be no consensus on the best timing for surgical intervention. Elliott and Shafiq performed a Cochrane review and found that there are no prospective, randomized trials to answer the question of timing of surgery in infantile esotropia [4]. So, pediatric ophthalmologists use preferences learned during training, previous studies, and personal experience to drive their decision making. Cerman et al.[5] performed a retrospective review to try to determine optimal age of surgical intervention. They used the development of stereopsis as the treatment goal. Thirty-eight children between the age of 7 and 45 months with median follow up of 72 months (33–196 months) were included. There was a statistically significant difference in age between those who developed stereopsis and those who did not. The median age at the time of surgery for those with stereoacuity was 15 and 25 months for those without. All of the patients operated on before 13 months of age developed some level of stereoacuity and none operated on after 39 months of age developed stereopsis. Patients operated on before 16 months of age had a median stereoacuity of 480 s of arc. There was no statistically significant difference between groups in sex, refractive error, compliance with spectacle wear, preoperative angle, postoperative angle, or additional inferior oblique procedure. Receiver operating characteristic curve analysis was used to determine appropriate cut off value for predicting stereopsis, which was found to be 16 months of age. When surgical success was defined as within 5 prism diopters of orthotropia, sensitivity of 66.7% and specificity of 92.3% was found in predicting existence of stereopsis.

This further supports the many reports in the literature finding early intervention has improved probability of developing stereopsis in infantile esotropia [6–10].

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Standard surgical treatment

There are multiple surgical techniques used to treat infantile esotropia. Although it has been shown that bilateral medial rectus recessions greater than 5 mm are an acceptable treatment, many surgeons still opt for three to four muscle surgery for the treatment of infantile esotropia [11–14]. There are two studies in the recent literature that retrospectively looked at surgical outcomes. Bayramlar et al. performed a retrospective review of 18 patients with infantile esotropia with angle greater than 55 prism diopters, who underwent bilateral medial rectus recession and resection of the lateral rectus in the nondominant eye. Median age at surgery was 22 months (10–168 months). Orthotropia to within 10 prism diopters or less was achieved in 78% of patients with a median follow up of 32 months (5–63 months). No overcorrections occurred and 22% had reoperation for residual esotropia [14]. There are limitations with this study including: retrospective nature, low number of patients, no standard surgical dosage was used, cyclovertical procedure performed at the same time in one patient, and surgery was performed relatively late. Despite these issues, the outcome was acceptable. Magli et al.[15] retrospectively reviewed 576 infantile esotropia patients who underwent surgical treatment and had at least 5 years of follow up. They evaluated results based on the angle of deviation and tried to determine if a specific procedure had a distinct advantage. Surgical success was defined as: total success (orthotropia), partial success (within 10 prism diopters of orthotropia), unsuccessful (greater than 10 prism diopters of deviation). Many different types of surgical procedures were performed for data analysis including: bilateral medial rectus recession with unilateral lateral rectus resection; bilateral medial rectus recession with bilateral lateral rectus resection; bilateral medial rectus recession with bilateral lateral rectus resection and conjunctival recession; bilateral medial rectus recession with anteriorization of the inferior obliques; bilateral medial rectus recession with bilateral lateral rectus resection and anteriorization of the inferior obliques; and bilateral medial rectus recession with bilateral rectus resection and anteriorization of the inferior obliques and conjunctival recession. No procedure had a statistically significant advantage in any of the groups, which were divided by size of angle. Age at time of surgery was the only variable which was significant. The issues with this study include: retrospective nature, no randomization into surgical treatment groups, variable numbers within the surgical treatment groups (some groups had small numbers), and relatively late surgery. Although these studies do have some value, it is clear that a prospective, randomized, multicenter clinical trial to determine which surgical procedure is most effective is warranted.

Of interest, Park and Oh [16▪▪] looked at surgical outcome of children with infantile esotropia in 56 preterm infants and compared results to 162 full-term infants. In their term cohort, a standard surgical table and numbers were used [17]. In the preterm cohort, if the infant was born at less than 30 weeks’ gestation, the surgical dose was decreased by 0.5 mm per muscle. Patients had a bilateral medial rectus recession unless their deviation was less than or equal to 20 prism diopters, then they had a unilateral medial rectus recession. Success was defined as alignment with in 10 prism diopters of orthotropia. Repeat surgery was recommended if constant esotropia of 20 prism diopters or greater was present for 6 months or if a constant exotropia of 15 prism diopters or greater occurred. In the preterm group, 5% underwent reoperation for residual esotropia and 20% for exotropia. In the term group, 14% underwent reoperation for residual esotropia and 9% for exotropia. There was a statistically significant difference in the rate of overcorrection with the preterm infants having greater overcorrection. Of interest, it appeared that overcorrection plateaued in term infants with time but continued to progress in preterm infants. In addition, significant neurologic impairments affected final outcome in both groups. Factors associated with final undercorrection were greater preoperative angle and younger age at surgery. The authors also compared surgical dose response and found a significant difference between the two groups: 3.99 prism diopters per mm in term infants and 4.40 prism diopters per mm in preterm infants. Analysis also showed a significant difference in patients with and without major neurological impairment: 3.94 and 4.24 prism diopters per mm, respectively. This study raises the very interesting question of whether we should approach preterm infants and patients with neurological disorders differently than term infants.

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Botulinum toxin A in infantile esotropia

The use of botulinum toxin appears to be an emerging therapy for the surgical treatment of strabismus. A recent Cochrane review by Rowe and Noonan [18] looked at randomized controlled trials of the use of botulinum toxin for the treatment of strabismus. They found four trials, two of which found no treatment outcome difference in the retreatment of acquired and infantile esotropia. One trial showed no evidence for the prophylactic use of botulinum toxin in acute onset cranial nerve six palsy. Finally, one trial showed poorer response than surgery for the treatment of horizontal strabismus in patients with no binocular vision. Of interest, the complication rate (ptosis, vertical deviation, diplopia, and subconjunctival hemorrhage) was reported to be between 24 and 55%. The current review is focused on the use of botulinum toxin in infantile esotropia only. Gursoy et al. performed a retrospective review of 56 patients treated before 24 months with either botulinum toxin or bilateral medial rectus recession and at least 48 month follow up. The surgical dose used was according to Helveston [19]. Botulinum toxin treatment dosage was 4.0 units on initial injection and 2.5 units for reinjection. Success was defined as alignment within 10 prism diopters of orthotropia at the time of last examination with up to three injections or a single surgical procedure. Although there was no statistically significant difference in the outcome, 77% of the surgical group and 68% of the botulinum toxin group had success. Stereopsis was essentially equal between the groups. Of interest, the average number of injections in the successfully treated group was 1.4 and transient ptosis was reported in 32% of the eyes. Lueder et al.[20] retrospectively reviewed 23 patients with large angle (greater than 65 prism diopters) infantile esotropia treated with bilateral medial rectus recession augmented with botulinum toxin and had at least 3-year follow up. Their treatment consisted of bilateral medial rectus recession with augmentation of 1.25 units in 1 muscle for patients with 65–70 prism diopters of esotropia and 2.5 units in patients with greater than 70 prism diopters of esotropia. Seventy-four percent of the patients had treatment success with a mean follow up of 6.6 years.

Proponents of botulinum toxin argue that reduced anesthesia time gives it a distinct advantage. This thought must be tempered by the understanding that anesthetic risk primarily occurs during induction and emergence. Given the temporary nature of the drug, multiple treatments are sometimes required. Another important issue is the side effects of ptosis and induction of vertical strabismus. This is especially important in this group of patients as they are in the amblyogenic age.

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Associated clinical findings

The association of dissociated vertical deviation (DVD), inferior oblique overaction, and latent nystagmus with infantile esotropia is well known. DVD is thought to manifest when binocular visual input is interrupted and is the slow elevation usually accompanied by extorsion of the nonfixing eye. Shin and Paik sought to determine if factors influencing the development of DVD could be identified. They performed a retrospective review of 90 patients with infantile esotropia who underwent surgical correction and developed DVD [21▪]. They found 38% of patients developed manifest DVD. The mean age at surgery for the manifest DVD group was 33 months compared to 21 months in the no DVD group, which was statistically significant. The mean preoperative angle was also significant with the DVD group being 50 prism diopters and the no DVD group being 40 prism diopters. When multivariate analysis was performed, the association of DVD with later surgery and large preoperative angle remained. Amblyopia was not different between groups.

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CONCLUSION

Although the body of work defining the timing of surgical treatment in infantile esotropia is mainly that of retrospective studies, the results seem compelling that treatment before age 2, and possibly younger, improves outcomes when development of stereopsis is the goal. The best surgical approach has yet to be clearly defined and the role of botulinum toxin remains questionable. It is clear that a prospective randomized multicenter controlled study should be performed to help define the best surgical approach and one to define if botulinum toxin should play a role in the treatment armamentarium.

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Acknowledgements

None.

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Financial support and sponsorship

None.

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Conflicts of interest

There are no conflicts of interest.

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REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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REFERENCES

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4. Elliott S, Shafiq A. Interventions for infantile esotropia. Cochrane Database Sys Rev 2013; 7:CD004917.
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14. Bayramlar H, Karaday R, Yildirim A, et al. Medium-term outcomes of three horizontal muscle surgery in large-angle infantile esotropia. J Pediatr Ophthalmol Strabismus 2014; 51:160–164.
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16▪▪. Park KA, Oh SY. Long-term surgical outcomes of infantile-onset esotropia in preterm patients compared with full-term. Br J Ophthalmol 2014; 0:1–6.

This suggests that premature infants may have a different response to surgical intervention than the normal term population. Perhaps they should be approached as a different cohort in terms of using standard surgical tables.

17. Parks M, Wright KW. Wright KW, Spiegel PH. Tables. Pediatric ophthalmology and strabismus Springer-Verlag, Inc., 2nd edn.New York, USA:2003.
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20. Lueder GT, Galli M, Tychen L, et al. Long-term results of botulinum toxin-augmented medial rectus recessions for large-angle infantile esotropia. Am J Ophthalmology 2012; 153:560–563.
21▪. Shin KH, Paik HJ. Factors influencing the development and severity of dissociated vertical deviation in patients with infantile esotropia. J AAPOS 2014; 18:389–391.
Keywords:

botulinum toxin; infantile esotropia; surgical treatment

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