Treatment of Younger Patients with Accommodative Esotropia

Background: Accommodative esotropia (AET) is a common disease during childhood. In this literature review, we analyze and discuss the different methods of treatment for Accommodative esotropia. Methods: Articles about accommodative esotropia from 2007 to 2017 were retrieved from the PubMed database. We study the articles by title/abstract/all fields, after applying the inclusion and exclusion criteria, finally 9 articles were retained. We compared the effectiveness between these approaches to treatment. Results: All the refraction methods had an effectivity rate of > 50%. The bifocal lenses group showed a higher failure rate (15.58%) than the single-vision lenses group (5.19%). Extraocular muscle surgery can significantly decrease deviation in patients who have AET with a high AC/A ratio (95.24%,71.30%,78.40%). After Botulinum toxin injection, the residual deviation was significantly lower than that before the injection (90.44%) and this rate held stable until 12 months after the injection (85.71%) and then decreased to 71.43% at 18 months. The effectivity rate in the prism builders group (surgery with prism group) was significantly higher than that in the prism non-builders group 100% vs. 56.25%). In this review, the average rate of Amblyopia in the accommodative esotropia patient is 41.36%. ConclusionsAll the treatment were full or partly effective for accommodative esotropia patients. Early intervention using effective methods of treatment can improve accommodative esotropia patients’ alignment and improve their quality of life. Amblyopia is common in patients with partly accommodative esotropia. High AC/A accommodative convergence to accommodation ratio ), Amblyopia.

refractive AET, the most common treatment is bifocal spectacles. When an increase in bifocal power does not eliminate the angle of deviation, base-out prisms may need to be used. [3] Strabismus surgery may also be necessary. In patients with partly accommodative esotropia (PAE), the most common treatment comprises full correction of the hyperopic refractive error measured under cycloplegia. The use of prisms and surgical correction for residual deviation may also be warranted. [1,2,13,14] In addition, treatment of any amblyopia should be considered.
There are several treatments for different type of AET. So analyze and discuss the difference among those treatments, and choose an effective method is very important.
Inclusion criteria were as follows: (1) All patients had AET; (2) Studies or reports discussed the treatment of AET; (3) Published in English.
Exclusion criteria were as follows: (1) Studies or reports published more than 10 years ago; (2) Subjects (participants) were over 18 years old; (3) Patients had undergone prior strabismus surgery (except in prism studies); (4) Patients had a chromosomal anomaly; (5) Study involved a follow-up period of < 5 months.
After applying the inclusion and exclusion criteria, finally 9 articles were retained. The basic information of the nine articles is listed in Table 1.  thus, to facilitate statistics in the present review, we defined its effectivity rate as 1 -failure rate  Table 3. Both surgical techniques can significantly decrease deviation in patients who have AET with a high AC/A ratio(95.24%,71.30%,78.40%). The PF with MR recession surgery had a higher effectivity rate than the PF without MR recession surgery. The incidence of residual esotropia was significantly higher than that of secondary exotropia in both studies. PF with MR recession surgery was more often associated with secondary exotropia, while PF without MR recession surgery was more often associated with residual esotropia. Before surgery, the patients in the PF with MR recession group had a bigger angle size than those in the PF without MR recession group at both near and distance. There was no significant change in either group after surgery. Akar (2013) reported that the PF without MR recession group showed that PF was associated with a slight decline from the early to late postoperative periods. injection, the residual deviation was significantly lower than that before the injection. The highest effectivity rate (90.44%), defined as "satisfactory," occurred at 6 months; this rate held stable until 12 months after surgery (85.71%) and then decreased to 71.43% at 18 months. The secondary exotropia rate after Botulinum toxin injection decreased over time, and the condition was eliminated at 6 months. In the first 3 months, the secondary exotropia rate was significant, especially during the first week (71.43%; Figure 2).
In the Quigley study (2017), the total effectivity rate of surgery with or without a prism was 73.08%.
The effectivity rate in the prism builders group (study group) was significantly higher than that in the prism non-builders group (control group; 100% vs. 56.25%, respectively).
In the Chun (2007) study, the researchers found that, after occlusion therapy, the deviation angle decreased while visual acuity increased in the amblyopic eye. They also found a statistically significant relationship between the two (Y = -19.359X -1.0545; R2 = 0.2498). Before occlusion therapy, 82% of patients were considered as indicating surgery, defined as a deviation angle of ≥ 15 pd within surgical limits. However, after occlusion treatment, that ratio decreased to 41% (p = 0.003).
They also found that, before occlusion therapy, deviation in the non-surgery group was significantly lower than that in the surgery group (15.62 pd vs. 25 pd, respectively). While the deviation angle decreased in the non-surgery group (from 15.62 pd to 2.46 pd, respectively) during the occlusion period, it was slightly increased in the surgery group (from 25 pd to 26.11 pd).
In the present review, seven of the nine studies mentioned amblyopia. The Chun (2007) study required that all patients have moderate amblyopia. Therefore, it was not used in the present review to analyze the effectiveness of amblyopia treatment. There were six articles remaining that analyzed the amblyopia rate among patients with AET. We found that amblyopia was common in AET, with an average rate of 41.36%. All six of the articles had an amblyopia rate of > 30% (Figure 3).

Discussion
The patients with partly accommodative esotropia showed only a reduced angle of esotropia with complete refractive correction. In other words, partly accommodative esotropia is a combination of both RAE and non-refractive accommodative esotropia. The major treatment methods for high AC/A ratio or partly accommodative esotropia are summarized in Figure 4.

Single vision lenses
Single vision lenses are the major method of full cycloplegic hyperopic correction to treat hypermetropic refractive error. Single vision lenses have the advantage of being economical, effective, easy to fit, simple to prescribe, and easy to access.
In the Gerling study (2013), [19] the authors found that no patients in either study group-the high AC/A ratio or control group (refractive esotropia group)-showed deterioration in the size of deviation.
Both groups showed a significant decrease in deviation. The effectivity rate in the experimental group (65.21%) was lower than that in the control group (85.71%), indicating that single-vision lenses are effective at treating deviations, even in patients with a high AC/A ratio. However, the effectivity rate in patients with a high AC/A ratio was lower than that in patients with a normal AC/A ratio. In both groups, there was a decrease in the participants' hyperopic refraction error.
In the Mohan study (2014), [16] which had a long term follow-up of > 10 years, the authors found no statistically significant difference in the mean interval between presentation and prescription of full hyperopic correction. The study by Watanabe-Numata et al. [24] found that the patients' age at the start of hyperopic correction was not a risk factor for treatment of RAE. Therefore, it is never too late to treat AET. Mohan (2014) showed that, even after a longer follow-up period (> 10 years), full cycloplegic hyperopic correction had a high success rate (79%) in the treatment of RAE and a low rate of further strabismus surgery (only 6%). We found a similar result in some of the other papers. [24] Full cycloplegic hyperopic correction is the first line AET treatment, especially in patients who have AET with a normal AC/A ratio. Therefore, patients can benefit from both alignment and hyperopic control.
Both the Gerling (2013) and Mohan (2014)  In the Gerling study (2013), after a long-term follow-up period (> 5 years), compared with the control group, the experimental group had almost twice as many patients who were still tropic and had deviations that were more difficult to control at near. Additionally, in the same study, the researchers found that, after the 5-year follow-up visit, single-vision lenses had no negative impact on the development of stereopsis, while the control group had more patients with stereopsis, whether gross or fine. In patients who had a high AC/A ratio, it may be necessary to use other treatment modalities to improve the effectivity rate of treatment. Conversely, the study was limited because there was no comparison group comprising patients with high AC/A esotropia who had been treated using bifocals, so there were not enough data to allow comparison of the effectivity rate between single-vision lenses and bifocal lenses.

Bifocal lenses
In patients who have AET with high AC/A ratio, full hyperopic correction often controls alignment at distance while allowing a deviation to persist at near. To reduce or eliminate the residual angle at near, bifocal lenses with an add-on near lens have been recommended. Bifocal lenses that correct the full cycloplegic refraction with the addition of between +2.00 D and +3.00 D are the commonest treatment method for high AC/A AET. [1,2,26] In the present study, bifocal lenses were somewhat controversial in the treatment of high AC/A ratio AET. The Whitman study (2016) reported that, although bifocal lenses were widely used to treat AET, there was no evidence to suggest that they showed better outcomes in children with high AC/A ratio AET than single-vision lenses or surgery. [27] In the same report, the group of children with bifocals had higher rates of surgery (15.6%) and a smaller improvement in near deviation over time than the single-vision lenses group. Surgical patients tended to be younger and have higher initial angle size.

The authors believed that patients (especially children) often have difficulty using bifocal lenses
properly. Some patients who have worn bifocals for long periods will adjust their head position to use the bifocal lens. Thus, they lose some fusional divergence and require the bifocal lens to retain binocular vision at near. This can cause them to lose accommodative capacity. However, single-vision wearers learn to control their deviations more effectively over the range from near to distance, possibly reducing the risk of decompensation to the point of requiring further extraocular muscle surgery.
The Whitman study (2016) showed that patients in the bifocal group who remained esotropic at near after prescription of a +3.00 D add-on seemed to have a higher risk of poor outcome than those in the single-vision group. They demonstrated that control of esodeviation at distance (< 10 pd) using full hyperopic correction is adequate for development of stereopsis, even if a large residual deviation persists at near. In Arnoldi's study, only 20% of patients who were assessed as good candidates for bifocals were long-term successes. In this regard, there are economic factors to consider as well. The cost of bifocal lenses is significantly higher than that of single-vision lenses. Therefore, in future clinical practice, doctors should more stringently restrict the indications for bifocal lenses.

Progressive-addition lenses
The use of PALs to treat AET has also been mentioned in many studies, [28] usually as an alternative to conventional bifocals. PALs add near and intermediate distances, so they are better for sports.
Additionally, patients have no esthetic problems with PALs, such as the line that is visible in bifocal lenses. [3] In the Mezer study (2015), the PAL-only group showed a significantly higher effectivity rate than the group that used bifocals first and then switched to PAL (100% vs. 56%). Additionally, there was no statistical significant between the two groups in terms of stereopsis.
PALs also had several disadvantages. They cost more than bifocal lenses and single-vision lenses.
They required frequent changing due to changes in the prescription or lens breakage. [3] Opticians usually have limited experience in fitting children with PALs, and the process is more challenging than fitting an adult with a PAL. [20]

Contact lenses
Contact lenses have been used as an alternative approach to treating AET. Monovision contact lenses, bifocal contact lenses, and the uni-lens RGP(Rigid Gas Permeable) aspheric multifocal contact lens have been mentioned in several studies. [29] Children with hyperopic refractive error who wear contact lenses requires less accommodation per unit distance than those who wear spectacle corrections. Additionally, contact lenses avoid the base-out effect at near that happens with high-plus glasses. [3] Unfortunately, contact lenses put patients at a higher risk of developing infections than glasses do. This requires patients with contact lenses to practice good compliance and good hygiene habits.
Morton et al. [29] showed that, in esotropia patients with a high AC/A ratio, neither bifocal nor multifocal contact lenses sufficiently control near deviation. Few studies discussed contact lenses in the treatment of AET. More clinical trials regarding the use of contact lenses in the treatment of AET are required to elucidate the efficacy of this modality of treatment.

Extraocular muscle surgery
Extraocular muscle surgery is not necessary in patients with RAE. It is an option when the residual deviation exceeds 15 pd after full cycloplegic hyperopic correction that is cosmetically displeasing. [3] The traditional surgical procedures for high AC/A ratio AET patients include augmentation of MR recession, slanted MR recession, and MR recession with Faden operation/scleral PF. [30][31] The Ghali study (2017) also mentioned recession-retroequatorial myopexy of the MR muscles. However, they found that this type of the surgery was less safe and less effective than the traditional surgeries. [32] Past studies have demonstrated that scleral PF does not progressively reduce peak saccadic velocity in the MR muscles' field of action. Wabulembo (2012) and Akar (2013) both mentioned extraocular muscle surgery as a major treatment for high AC/A ratio AET, and the effectivity rate was satisfactory in both studies. Both types of surgery can significantly decrease the deviation at near or distance. Indeed, the deviation angle is close to zero even in the later post-operative period. In a recent study, Inal (2017) also came to the same conclusion. [33] Wabulembo (2012) and Akar (2013) found that the pre-operative deviation angle in the PF with MR recession group was larger than that in the PF without MR recession group-both at near and distance. After the surgery, they found no significant difference in deviation between the two groups.
However, in the PF with MR recession group, the effects of the PF slightly declined over time. Some researchers found during the secondary surgery of some Faden operations that the scar between the muscle and the sclera had gradually moved anteriorly. [34] This discovery may explain why the effects of PF slightly decline over time.
Both extraocular muscle operations are effective methods for treating high AC/A ratio AET. However, PF with MR recession confers a larger correction of the deviation. Specifically, the PF with MR recession surgery group showed a higher incidence of secondary exotropia (7.9% vs. 4.6%) and a lower rate of residual esotropia (13.7% vs 24.7%) than the PF without MR recession group. The residual esotropia rates were similar in the both studies (14.29% and 13.70%, respectively).
Additionally, residual esotropia rates in both groups were lower than those of other non-surgery operations, which have reported rates of 12%-30%. [22] Akar ( Some studies have also mentioned slipped MR muscle, which is a serious and rare potential complication of extraocular muscle surgery. [35] Nonetheless, the complications of extraocular muscle surgery were rare and mild in the studies. However, the surgeon's surgical technique, patient compliance, and a strict follow-up procedure were important.

Botulinum toxin
Injecting Botulinum toxin into the extraocular muscles alters ocular alignment, producing temporary palsy and an overcorrection of strabismus, which in turn leads to a shortening of the antagonist muscle. Histology studies have shown that density changes in the sarcomeres enhance permanent ocular alignment. [36] Indeed, the deviation before botulinum toxin type A injection was significant lower than in extraocular muscle surgery studies. [21,22] The Flores study (2016) showed a significant decrease in deviation after Botulinum toxin injection. The toxin's most effective period is from 6 months to 12 months. Because Flores (2016) did not report a long term follow-up period in their study, we only found a downward trend in effectivity rate, implying that some patients may require extra injection in the future. The secondary exotropia rates decreased over time. The main observed side effects in the study were reversible ptosis, temporary diplopia, and the development of a vertical deviation. The authors also had to consider that the recovery time from adverse effects was between 2 and 3 weeks, perhaps reflecting Botulinum toxin metabolism. [37] The advantages of Botulinum toxin were that it is cost effective and a good choice for patients in whom surgery is contraindicated. The main disadvantage was that it may not remain stable over a long period; thus, further treatment may be required. Additionally, there are potential side effects, such as reversible ptosis, diplopia, and vertical deviation. Flores' study was prospective in design.
However, the sample size was not large enough and the follow-up period was not long enough.

3..1. Prism
Some studies reported that the prism adaptation test can improve surgical outcomes, showing that a small angle of residual esotropia can be managed using non-surgical treatment such as prism glasses. [38] Quigley (2017) showed a significantly higher effectivity rate of surgery (100%) in the prism builders group than in the surgery without prism group (56.25%). The authors also found that prism builders were younger than prism non-builders (median age: 4.5 vs. 6 years), which may influence surgical outcome. Patients with a high AC/A ratio have an increased requirement for prisms, and postoperative outcomes were better than those of patients with a lower AC/A ratio.

Occlusion therapy
Amblyopia is usually associated with anisometropia or unilateral and constant esotropia. Partly accommodative esotropia usually involves a constant and unilateral deviation. Therefore, amblyopia is common in patients with partly accommodative esotropia. Occlusion therapy is recommended in patients with partly accommodative esotropic moderate amblyopia. [40] Current clinical guidelines recommend initiating amblyopia treatment before surgical correction of strabismus. [41] Chun (2007) showed a statistically significant relationship between increases in visual acuity in amblyopic eyes and decreases in the deviation angle (p = 0.024). This may have occurred because increases in visual acuity in patients with amblyopic eyes confer better fusional divergence and thus better control of deviation. The same study showed a significant decrease in angle size in the nonsurgery group, whose deviation with glasses was almost lower than 20 pd during the occlusion period.
In the surgery group with a higher deviation before occlusion therapy, the deviation was slightly increased, suggesting that occlusion therapy is more beneficial in those with lower deviation AET.

Amblyopia treatment
Amblyopia is defined as a best corrected visual acuity of less than 20/20 in the absence of any obvious structural or pathological disease, but with one or more of the following amblyogenic factors occurring before the age of 6 years: anisometropia, constant unilateral strabismus, amblyogenic bilateral isometropia, amblyogenic astigmatism, or image degradation. Amblyopia can cause decreases in visual acuity, saccades and pursuits abnormality, accommodative status problems, spatial distortion, performance with reduced illumination and contrast sensitivity, crowding phenomenon, laser interferometry acuity, or electrophysiological testing deficiencies compared with the dominant eye.
The prevalence of amblyopia is 1%-5% worldwide. Among patients with this condition, 91% have unilateral amblyopia with strabismus, hyperopia of ≥ 2.0 D, astigmatism of ≥ 1.0 D, or anisometropia of ≥ 0.5 D, while 76% of children with bilateral amblyopia have bilateral hyperopia of ≥ 3.0 D or astigmatism of ≥ 1.0 D. Hyperopia (usually greater than +2.00) is a common risk factor for developing AET. Amblyopia is common in patients with AET, especially in those with partly accommodative esotropia. In the present review, we found that the average amblyopia rate was 41.36%. Amblyopia rates were above 30% in six articles. Clinically, we need to carefully consider the diagnosis of amblyopia in patients with AET, and amblyopia treatment must be considered during treatment of accommodative esotropia with amblyopia.
The treatment of amblyopia includes correction of refractive error, occlusion therapy, vision therapy, and treatment of strabismus. In the present review, correction of cycloplegic refractive error, followed by occlusion therapy, was the commonest method for treating patients who had accommodative esotropia with amblyopia. Other methods were mentioned, such as atropine-only treatment, patching followed by atropine treatment, and cycloplegic refraction. However, several studies reported abruptly developed esotropia after full-time occlusion treatment. The studies authors' speculated that this phenomenon was caused by disruption of peripheral fusion. [42]

Limitations
This literature review had some limitations: (1) Most reports included were retrospective; (2) There were no uniform standard criteria to define effectivity rate, inclusion, or exclusion; (3) None of the nine articles were large randomized controlled trials; (4) Some studies' sample sizes were not large enough, which may have generated a higher rate of random error.

6.Future studies
More large sample-size, randomized controlled trials are required. In particular, investigators need to form a unified standard of inclusion and exclusion criteria, as well as choose comparable treatment methods. Negative results should also be analyzed and considered, and long-term follow-up periods are needed.

Conclusion
Full cycloplegic hyperopic correction is the first line of the treatment for AET. Single-vision lenses have satisfactory results in the treatment of RAE. However, they may result in decompensation.Bifocal lenses are one of the most common effective treatment methods for high AC/A AET. However, children often have difficulty using bifocal lenses properly. Therefore, optometrists and parents need to monitor children's behavior carefully. PALs can be an alternative to lined bifocals in the treatment of AET. They can be beneficial for athletes and patients who really care about esthetics. However, because they are expensive, require frequent changes, and are more difficult to fit, PALs should not be used in younger patients.Contact lenses have a theoretical advantage over spectacle lenses in the treatment of AET. They require less accommodation per unit distance and avoid the base-out effect at near. However, to date, few clinical studies have been carried out in this regard.
Extraocular muscle surgery is an option in patients whose deviation angle is over 15 pd after full cycloplegic hyperopic correction. The Faden operation, with or without MR muscle recession, is an effective method for the treatment of AET with high AC/A ratio. Alternatively, PF with MR recession can confer a larger correction of deviation, while PF without MR recession has a lower rate of secondary exotropia development. Botulinum toxin treatment of AET is effective for at least 18 months. It is a good choice in patients who have contraindications to surgery. However, such patients may not remain stable for a long time and may therefore require further treatment.
Prism treatment is a complementary method that improves surgical outcomes after extraocular muscle surgery. Prisms can be used to fine-tune surgical dosage and reduce undercorrection and overcorrection in partly accommodative esotropia. However, further addition of prisms may increase deviation. Figure 1 Effectivity rates of the various studies Figure 2 Satisfactory rate vs. exotropia after botulinum toxin injection Figure 3 Amblyopia rate in AET patients Various treatments for patients who have accommodative esotropia with high AC/A ratio