Effectiveness of treatment modalities for childhood esotropia: a systematic review

Study design

This systematic review was reported in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews (PRISMA, 2020) (Page et al., 2021). The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024589042. The researchers conducted a comprehensive search across multiple online databases, including PubMed, Web of Science, ProQuest, Scopus, Google Scholar, EBSCO, and Medline, covering studies published from January 1990 to December 2023. The quality of each study included in this review was assessed using the evaluation tool developed by Downs & Black (1998). Additionally, each selected article underwent a thorough review process and was assigned a score on a scale of 1 to 10, as shown in Table 1. This review included a diverse range of articles to evaluate various treatment approaches for different forms of childhood esotropia, conducted across multiple countries and involving children from diverse age groups.

Search strategy and selection criteria

The search keywords in this systematic review were applied using Boolean operators (OR/AND). Six databases were searched for studies published between January 1990 and December 2023, using the following MeSH (Medical Subject Heading) terms and keywords: (Refractive correction OR Optical correction) OR (Single vision lenses OR Bifocal lenses OR Progressive-addition lenses OR Contact lenses) OR (Surgical methods OR Extraocular muscle surgery) OR (Botulinum toxin therapy OR drug therapy) OR (Prism therapy OR Optical correction) OR (Surgical treatment) AND Childhood esotropia (Infantile esotropia OR Congenital esotropia OR Accommodative esotropia OR Refractive esotropia OR Non-refractive accommodative esotropia OR Partially accommodative esotropia).

Eligibility and inclusion criteria

The scope of this review was restricted to scholarly articles published in peer-reviewed journals and written in English. Only studies focused on treating childhood esotropia using various management options for different types of esotropia were included. Articles that did not focus on children or did not evaluate esotropia treatments were excluded. Additionally, meeting abstracts, editorial discussions, conference papers, and studies lacking essential data collection were excluded, as illustrated in Fig. 1.

Data extraction

Researchers Saif Alrasheed and Naveen Challa evaluated the titles and abstracts of all articles included in the review, using a standardized form to record information such as the first author’s name, publication year, country of study, subject characteristics (age, sample size), types of childhood esotropia, treatment methods, and the success rate of each treatment modality. In this study, success was defined as a post-treatment deviation of less than 10 prism dioptres (PD) following intervention (optical correction, extraocular muscle surgery, and botulinum toxin injection). In this systematic review, specific standards and protocols were established to manage disagreements among authors and guide the review process. These protocols fostered transparent communication, enabling authors to express differing perspectives and resolve conflicts by adhering to predefined guidelines. Any disagreements between authors were discussed and resolved based on objective criteria rather than assumptions or opinions. If a conflict remained unresolved after discussions, an external referee Abdelaziz Elmadina, serving as a neutral expert in the field, was consulted to provide insight and resolve the issue.

Risk of bias assessment

The quality of each study included in this systematic review was assessed using the evaluation tool developed by Downs & Black (1998). Additionally, Egger and Begg tests were applied to evaluate the risk of bias in the selected studies. Two review authors, Saif Alrasheed and Naveen Challa, independently conducted the bias assessment, and any discrepancies were resolved through discussion, with a third author Saeed Aljohani consulted when necessary.

Study characteristics

A total of 3,605 articles were initially identified, as shown in Fig. 1. After removing duplicates, the titles of 2,457 articles were screened. Of these, 2,370 were excluded based on abstract review as they did not meet the inclusion criteria. An additional 53 articles were excluded for being conference abstracts, review articles, or book chapters, or because essential information could not be extracted, as shown in Fig. 1. The final systematic review included 34 quality-assessed studies (Mohney et al., 2011; Page et al., 2021; Downs & Black, 1998; Gerling & Arnoldi, 2013; Mohan & Sharma, 2014; Whitman, MacNeill & Hunter, 2016; Mezera, Wygnanski-Jaffe & Stolovich, 2015; Sreelatha et al., 2022; Iqbal, Hussain & Qazi, 2013; Mulvihill et al., 2000; Krishnamoorthy, 2019; Choe, Yang & Hwang, 2019; Kekunnaya, Velez & Pineles, 2013; Lambert et al., 2003; Yun-chun & Longqian, 2011; Wabulembo & Demer, 2012; Akar et al., 2013; Pensiero et al., 2021; Alshamlan et al., 2021; AlShammari, Alaam & Alfreihi, 2022; Scott et al., 1990; De Alba Campomanes, Binenbaum & Eguiarte, 2010; McNeer, Tucker & Spencer, 1997; Campos, Schiavi & Bellusci, 2000; Gursoy et al., 2012; Flores-Reyes et al., 2016; Arnoldi, 2002; Alam et al., 2023; De Alba Campomanes, Binenbaum & Eguiarte, 2010; Wan et al., 2017; Gama et al., 2020; Jiang et al., 2023; Shi et al., 2021; Bayramlar et al., 2014; Elkhawaga et al., 2022; Kim & Choi, 2017) from 14 countries, as summarized in Table 1. These studies were published between 1990 and 2023 and encompassed a total sample size of 3,877 children with a mean age of 4.72 ± 2.08 years. During the literature review and our examination of articles included in the study, we found that most studies defined treatment success as a deviation of less than 10 prism dioptres.

The reviewed studies (Mohney et al., 2011; Page et al., 2021; Downs & Black, 1998; Gerling & Arnoldi, 2013; Mohan & Sharma, 2014; Whitman, MacNeill & Hunter, 2016; Mezera, Wygnanski-Jaffe & Stolovich, 2015; Sreelatha et al., 2022; Iqbal, Hussain & Qazi, 2013; Mulvihill et al., 2000; Krishnamoorthy, 2019; Choe, Yang & Hwang, 2019; Kekunnaya, Velez & Pineles, 2013; Lambert et al., 2003; Yun-chun & Longqian, 2011) (Table 2) demonstrated that optical correction methods, including single vision lenses, bifocal lenses, progressive-addition lenses, and prismatic correction, achieved a higher success rate of 79.31% in treating childhood esotropia after an average follow-up period of 5.57 years.

Extraocular muscle surgery demonstrated an effectiveness rate of 71.4% over a follow-up period of 2.89 years. Meanwhile, botulinum toxin injection showed a lower effectiveness rate of 61.24% after a follow-up period of 3.15 years, as shown in Tables 2, 3 and 4.

Publication bias

Egger and Begg tests were conducted to assess the publication bias. The outcomes showed that both tests indicated no significant bias. The results of Begg’s test (P = 0.865) and Egger’s test (P = 0.512) suggested that there is no strong evidence of publication bias in the studies that examined various treatment modalities for childhood esotropia.

Optical correction for treatment of childhood esotropia

Bifocal lenses

Children with a high AC/A ratio and AET often achieve controlled alignment at a distance with full hyperopic correction, though a deviation may persist at near fixation. To eliminate this, bifocal lenses with additional near power are recommended to reduce the residual angle at near fixation. The most common treatment method for high AC/A AET includes bifocal lenses that correct the full cycloplegic refraction with additional power ranging from +2.00 D to +3.00 D (Whitman, MacNeill & Hunter, 2016; Ludwig et al., 2005). Whitman, MacNeill & Hunter (2016) evaluated whether treatment with bifocal glasses over a 5.5-year period, compared to single-vision lenses, improved stereopsis outcomes in individuals with high AC/A ratio accommodative esotropia. They concluded that bifocals did not improve stereopsis outcomes compared with single-vision lenses, and there is no evidence that bifocals enhance sensory outcomes in children with high AC/A ratio accommodative esotropia.

Whitman, MacNeill & Hunter (2016) noted that children may face challenges in using bifocal lenses, as some adjust their head position to depend on the bifocal segment, potentially resulting in a loss of fusional divergence and accommodative capacity. In contrast, children wearing single-vision lenses often effectively control their deviations at various distances, thereby reducing the likelihood of progression to a degree that would necessitate additional eye muscle surgery. Whitman, MacNeill & Hunter (2016) recommended that controlling esotropia to less than 10 PD at distance using full hyperopic correction is sufficient for stereopsis development, even if a significant residual esodeviation remains at near fixation. Arnoldi & Shainberg (2005) conducted a comparative study on the effects of bifocals, surgery, and single-vision lenses in children with high AC/A esotropia. The results indicated that children treated with either bifocals or single-vision lenses exhibited a 5 PD reduction in near esotropia, without a corresponding decrease in the AC/A ratio. However, children in the bifocal group were less likely to achieve emmetropization and tended to show an increase in the AC/A ratio over time. Surgery effectively reduced near deviations and eliminated the difference between distance and near deviations, though more children in the surgery group lost stereoacuity compared to those in the bifocal and single-vision lens groups. Arnoldi & Shainberg (2005) found that only a few children considered suitable for bifocal lenses achieved long-term success. Additionally, economic factors should be considered, as bifocal lenses are more expensive than single-vision lenses. Consequently, eye care professionals should consider limiting the use of bifocal lenses in future clinical practice.

Progressive addition lenses (PAL)

The primary benefit of progressive addition lenses (PAL) is their cosmetic appearance and support for natural accommodation development in children with high AC/A ratio accommodative esotropia. However, a significant drawback is the challenge of fitting young children with lenses designed for adults with presbyopia (Smith, 1985). Jacob et al. used PALs in managing children with esotropia associated with a high AC/A ratio and reported that most children experienced successful correction of their near esodeviation and achieved some level of stereopsis. Additionally, they adapted easily to wearing progressive lenses without difficulties (Jacob, Beaulieu & Brunet, 1980). Mezera, Wygnanski-Jaffe & Stolovich (2015) conducted a study on the effects of PAL and bifocals in treating esotropia with a high AC/A ratio in children with a mean age of 5.36 ± 2.68 years, over a 5-year follow-up period. They reported that PALs are highly effective in treating AET, achieving favourable sensory and motor outcomes. Similarly, both PALs and bifocals proved useful in the initial treatment of children with AET. However, economic factors should be considered, as PALs are more expensive than bifocal and single-vision lenses. Consequently, eye care specialists should take these factors into account more carefully when prescribing PALs.

Prismatic correction

Surgery is typically recommended for children with partially accommodative esotropia (PAET) if fusion cannot be achieved within 6–8 weeks of hyperopic correction or if a residual deviation greater than 10 PD remains at both near and distance with full correction. Prisms are often used as an alternative management approach for PAET (Wright & Spiegel, 2013). In a 1-year follow-up study of children with PAET, 44% of patients were able to maintain good alignment or esophoria using prism glasses alone, without requiring surgery, and none experienced a decline in stereoacuity (Han & Hwang, 2009). Additionally, in cases of consecutive esotropia following exotropia surgery, prismatic correction effectively achieved satisfactory motor alignment while preserving good stereoacuity (Lee, Yang & Hwang, 2015; Lee & Hwang, 2013).

Choe, Yang & Hwang (2019) investigated prismatic correction in managing PAET over a three-year follow-up, finding a success rate of 60.5%, and concluded that prism glasses may be beneficial for small-angle PAET with good near fusion. Similarly, Yun-chun & Longqian (2011) reported a success rate of 71.4% over a two-year follow-up in treating small residual angles of esotropia in PAET using prismatic correction. Prism can serve as an alternative for patients who cannot undergo surgery and may help control the discomfort of double vision. However, some researchers have suggested that increasing prism strength could potentially worsen the deviation.

Extraocular muscle surgery

The reviewed studies (Wabulembo & Demer, 2012; Akar et al., 2013; Pensiero et al., 2021; Alshamlan et al., 2021; AlShammari, Alaam & Alfreihi, 2022; Scott et al., 1990; de Alba Campomanes, Binenbaum & Eguiarte, 2010; McNeer, Tucker & Spencer, 1997; Campos, Schiavi & Bellusci, 2000; Gursoy et al., 2012; Flores-Reyes et al., 2016; Arnoldi, 2002; Alam et al., 2023; De Alba Campomanes, Binenbaum & Eguiarte, 2010; Wan et al., 2017; Gama et al., 2020; Jiang et al., 2023; Shi et al., 2021; Bayramlar et al., 2014; Elkhawaga et al., 2022; Kim & Choi, 2017) (Table 3) demonstrated that extraocular muscle surgery had a success rate of 71.4% in treating childhood esotropia after a follow-up period of 2.89 years. Robert & Rutstein (1998) noted that children with refractive accommodative esotropia (RAET) may not require extraocular muscle surgery; however, surgery becomes an option if a residual deviation greater than 15 PD remains after full cycloplegic hyperopic correction and poses cosmetic concerns. Traditional surgical options for children with AET associated with a high AC/A ratio include medial rectus (MR) recession with augmentation, slanted MR recession, and MR recession combined with a Faden operation or scleral posterior fixation (PF) (Wabulembo & Demer, 2012; Akar et al., 2013; Gharabaghi & Zanjani, 2006). In a study by Wabulembo & Demer (2012), the effectiveness of bilateral MR recession with a pulley PF procedure was evaluated in children with PAET. This study included children with a mean age of 4.3 ± 1.6 years, followed for 5.7 years, and reported a high success rate of 95.24%. The authors concluded that the procedure is both effective and safe, providing long-term outcomes that surpass those of other surgical approaches.

Akar et al. (2013) demonstrated a successful outcome of Faden operations for treating children with PAET over a 4.8-year follow-up. They concluded that Faden surgery, with or without muscle recession, is effective for PAET associated with a high AC/A ratio. Studies (Pensiero et al., 2021; Alshamlan et al., 2021; AlShammari, Alaam & Alfreihi, 2022; Scott et al., 1990; De Alba Campomanes, Binenbaum & Eguiarte, 2010; McNeer, Tucker & Spencer, 1997; Campos, Schiavi & Bellusci, 2000; Gursoy et al., 2012; Flores-Reyes et al., 2016; Arnoldi, 2002; Alam et al., 2023; De Alba Campomanes, Binenbaum & Eguiarte, 2010; Wan et al., 2017; Gama et al., 2020; Jiang et al., 2023; Shi et al., 2021; Bayramlar et al., 2014; Elkhawaga et al., 2022; Kim & Choi, 2017) conducted among children with various forms of esotropia, employing traditional extraocular muscle surgery or bilateral medial rectus (MR) recession, reported success rates ranging from 37% to 78%. In a study by Bayramlar et al. (2014), children aged 1–14 years with infantile esotropia (IET) who underwent bilateral MR recession over a three-year follow-up had a high success rate of 78%. The authors noted that three horizontal muscle surgeries for IET maintain high success in medium-term follow-up. In contrast, Arnoldi (2002) reported a lower success rate of 37% for bilateral MR recession in children with PAET. Arnoldi and colleagues concluded that surgical treatment for PAET can lead to overcorrection, resulting in consecutive exotropia following standard surgery. Findings from the aforementioned studies (Arnoldi, 2002; Bayramlar et al., 2014) indicated that bilateral MR recession achieved better outcomes in children with IET compared to those with PAET. Notably, the bilateral medial rectus fenestration procedure showed a high success rate of 88% in managing PAET. The authors concluded that the fenestration technique is effective in reducing the angle of deviation in PAET cases (Elkhawaga et al., 2022).

Botulinum toxin injection (BT)

The reviewed studies (Pensiero et al., 2021; Alshamlan et al., 2021; AlShammari, Alaam & Alfreihi, 2022; Scott et al., 1990; de Alba Campomanes, Binenbaum & Eguiarte, 2010; McNeer, Tucker & Spencer, 1997; Campos, Schiavi & Bellusci, 2000; Gursoy et al., 2012; Flores-Reyes et al., 2016; Arnoldi, 2002; Alam et al., 2023; De Alba Campomanes, Binenbaum & Eguiarte, 2010; Wan et al., 2017; Gama et al., 2020; Jiang et al., 2023; Shi et al., 2021) (Table 4) showed that bilateral botulinum toxin (BT) injections at various dosages achieved a 61.24% success rate in treating childhood esotropia over a follow-up period of 3.15 years. Injecting BT into the extraocular muscles induces temporary paralysis and overcorrection of the strabismus, which promotes shortening of the opposing muscle. Histological studies have demonstrated sarcomere density changes that enhance long-term ocular alignment (Kowal, Wong & Yahalom, 2007). BT type A has proven effective for small to moderate-angle esotropia, acute or chronic fourth and sixth nerve palsy, childhood strabismus, and thyroid eye disease. Pensiero et al. (2021) reported a lower success rate of 36.1% following BT chemo-denervation for children with IET over a one-year follow-up. They concluded that a single bilateral BT injection at age 2 is a recommended first-line treatment for IET without a vertical component. These studies (McNeer, Tucker & Spencer, 1997; Campos, Schiavi & Bellusci, 2000; Gursoy et al., 2012) conducted on children with IET using bilateral botulinum toxin (BT) injections reported high success rates ranging from 68% to 89%. McNeer, Tucker & Spencer (1997) found that BT injections effectively align the visual axes in infants and children with IET. In contrast, other studies (De Alba Campomanes, Binenbaum & Eguiarte, 2010; Gama et al., 2020) reported lower success rates of 21.1% and 45% for bilateral BT injections in treating IET. Bilateral BT injection is often recommended as an alternative rather than a definitive treatment for IET, particularly when the surgeon or parents are hesitant about early strabismus surgery.

Flores-Reyes et al. (2016) demonstrated a significant reduction in deviation following BT injection, with a success rate of 71.43%. The optimal effectiveness of the toxin spanned 6 to 12 months; however, the study’s follow-up period was limited to 1.5 years, lacking data on long-term outcomes. Flores concluded that BT is an effective long-term treatment for PAET but noted potential adverse effects, including vertical deviation, ptosis, and diplopia. Wan et al. (2017) reported a success rate of 58% for bilateral BT injections in treating children with acute-onset esotropia (AOCET) over a 1.5-year follow-up. Wan suggested that BT is as effective as surgery in treating AOCET after six months, with the added benefits of reduced anaesthesia time and healthcare costs. Additionally, Shi et al. (2021) reported a high success rate of 75% for bilateral BT injections in treating AOCET in children over three years. Shi and colleagues concluded that BT injections are effective for managing AOCET in both adults and children, providing results comparable to surgical intervention.

Patching and vision therapy

Strabismic amblyopia is commonly associated with childhood esotropia, particularly in those with partially accommodative esotropia (Mezera, Wygnanski-Jaffe & Stolovich, 2015). Clinically, eye care providers must carefully assess for amblyopia in children with esotropia. When accommodative esotropia is accompanied by amblyopia, treatment for amblyopia should be initiated concurrently with the management of the esotropia. The treatment of childhood amblyopia associated with esotropia typically involves a combination of refractive correction, occlusion therapy, and vision therapy. Interventions such as dichoptic and perceptual training have shown effectiveness in managing strabismic amblyopia (Alrasheed & Aldakhil, 2024). In this review, the most commonly employed approach for treating children with accommodative esotropia and amblyopia was the correction of cycloplegic refractive error, followed by occlusion therapy.

Limitations of study

Our systematic review had some limitations: firstly, some of the reviewed studies were retrospective in nature. Secondly, there was no consistent standard for defining effectiveness rates, or for setting inclusion and exclusion criteria. Thirdly, the studies varied in sample size, with some being small and others large, which may have increased the risk of random error. Additionally, the present review did not include amblyopia or the assessment of visual acuity, nor did it address the use of patching and vision therapy, which are common treatment modalities for childhood esotropia. We recommend that future research should prioritize more randomized controlled trials with larger sample sizes. These trials should adhere to standardized inclusion and exclusion criteria and use comparable treatment protocols. Additionally, implementing long-term follow-up periods will be crucial to gather comprehensive data on the various treatments for childhood esotropia. Despite these limitations, this review provides valuable and updated information on the effectiveness of different treatment modalities for improving ocular alignment in childhood esotropia.