Clinical Efficacy, Safety, and Success Factors of Botulinum Toxin Type A in the Treatment of Acute Acquired Comitant Esotropia

Clinical Efficacy, Safety, and Success Factors of Botulinum Toxin Type A in the Treatment of Acute Acquired Comitant Esotropia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Efficacy, Safety, and Success Factors of Botulinum Toxin Type A in the Treatment of Acute Acquired Comitant Esotropia Makiko Ui, Toshiaki Goseki, Ayumi Watanabe, Kinue Fueki, Yuko Komiya, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5596397/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Acute acquired comitant esotropia (AACE) is an increasingly reported form of esotropia, possibly linked to the rising use of digital devices. Botulinum toxin type A (BTXA) has emerged as a minimally invasive treatment alternative to surgery, particularly for patients who present with diplopia. This study retrospectively evaluated 228 patients with AACE who received BTXA injections at a single center. Treatment outcomes, adverse events, and factors influencing success were analyzed. The average patient age was 30.9 years, and 57% achieved successful outcomes, with 46% being cured and 11% showing improvement. Transient adverse events, including ptosis (24%) and hypertropia (16%), were observed. The study found that shorter duration from onset to treatment (P = 0.024) and post-treatment overcorrection (P = 0.001) were associated with higher success rates. Although some patients required additional treatments or surgery due to recurrence, BTXA proved to be an effective intervention for AACE, with a significant improvement in eye alignment and stereopsis. These findings suggest that early intervention with BTXA is crucial for successful outcomes and offers a safe, less invasive alternative to traditional strabismus surgery. Health sciences/Medical research Health sciences/Medical research/Outcomes research Acute acquired comitant esotropia (AACE) Botulinum toxin type A (BTXA) Strabismus Diplopia Eye alignment Stereopsis Success rate Success factors Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Acute acquired comitant esotropia (AACE) is a rare form of esotropia [ 1 ] . However, there has been a notable increase in reported cases in recent years, likely due to the rising use of digital devices, such as smartphones [ 2 – 6 ] . AACE typically manifests as late-onset esotropia with diplopia in individuals with normal binocular vision [ 7 ] . Unlike other forms of esotropia that usually appear in early childhood or are associated with significant hyperopic refractive errors or neurological issues, AACE typically occurs in older children and adults. It is characterized by late-onset esotropia with diplopia, consistent esotropia across all gaze directions, minimal or no significant hyperopia, and the absence of organic diseases such as brain tumors [ 1 , 8 ] . Neurological examinations and imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRIs), generally return normal results, distinguishing AACE from other causes of acute-onset esotropia. In recent years, Botulinum toxin type A (BTXA) injections have emerged as a less invasive alternative to traditional strabismus surgery [ 9 – 13 ] . BTXA temporarily paralyzes the overactive medial rectus muscles, allowing the eyes to realign. Studies have demonstrated that BTXA can effectively reduce esotropia and improve binocular function with a relatively low risk of complications. In some cases, the effects of BTXA extend beyond the drug's active period, leading to long-term alignment. However, it remains unclear which specific cases result in long-term success. Moreover, few large-scale studies have reported these outcomes. This study aims to investigate the efficacy and safety of BTXA injections in treating AACE while also identifying factors that contribute to successful treatment outcomes. Results Patient Demographics The study included 228 patients diagnosed with AACE who received their first BTXA injection at the CS Eye Clinic by the same surgeon. The patient demographics are presented in Table 1 . Table 1 Demographic and clinical characteristics of included patients Demographics All (n = 228) Age (years) - Mean ± SD 30.9 ± 11.9 - Median (min–max) 28 (12–75) Sex (male) , n (%) 93 (41%) Duration from onset to treatment (months) - Mean ± SD 54.8 ± 163.4 - Median (min–max) 36.5 (0.2–486.7) Distant Angle of Deviation (PD) - Mean ± SD 28.9 ± 14.2 - Median (min–max) 25 (4–95) Distant Qualitative Eye Position , n (%) - Esotropia 222 (97%) - Esophoria 6 (3%) Near Stereopsis , n (%) - Absent 76 (33%) - Present 152 (67%) Observation Period (months) - Mean ± SD 9.1 ± 8.2 - Median (min–max) 6.7 (0.0–36.4) The patients’ ages ranged from 12 to 75 years, with a mean age of 30.9 ± 11.9 years. The minimum age of 12 years was chosen because, in Japan, public health insurance covers BTXA treatment for strabismus only for patients aged ≥ 12 years. The study population comprised 93 (41%) males and 135 (59%) females. The duration from symptom onset to the initiation of BTXA treatment varied significantly, with a median time to treatment of 36.5 months (range: 0.2–486.7 months). The mean angle of esotropia at a distance was 28.9 ± 14.2 prism diopters (PD). Most patients (97%) exhibited stable esotropia at distance, while a small proportion (3%) had esophoria at distance. Near stereopsis was absent in 76 (33%) patients and present in 152 (67%) patients. The mean observation period was 9.1 ± 8.2 months. Injection Details A total of 318 BTXA injections were administered, with an average of 1.4 ± 0.8 injections per patient. The average dosage per injection was 2.7 ± 0.9 units (Table 2 ). Table 2 Injection Details Injection Details All (n = 318) Number of Injections (times per patient) 1.4 ± 0.8 Dosage (units per injection) 2.7 ± 0.9 The total number of injections was 318, with an average of 1.4 ± 0.8 injections per patient. The average dosage per injection was 2.7 ± 0.9 units. Treatment Outcomes The treatment outcomes of the 165 patients who were observed for more than 6 months after the initial injection are shown in Fig. 1 . Overall, 94 (57%) patients achieved successful outcomes. Among these, 76 (46%) patients were cured and 18 (11%) patients showed improvement. A subset of 40 (24%) patients required repeated injections because of esotropia recurrence. Surgery was performed in 27 (17%) patients who did not opt for additional BTXA injections owing to recurrence, inadequate response, or adverse events. Four (2%) patients showed no change in their condition for more than 6 months after the initial injection. Changes in Distant Angle of Deviation The changes in the distance angle of deviation over time are shown in Fig. 2 . Before the treatment, the mean angle of deviation was 28.6 ± 12.0 PD. One month after treatment, this angle significantly reduced to 2.3 ± 12.9 PD (P < 0.0001). At the final observation, the mean angle of deviation slightly increased to 10.2 ± 11.4 PD, indicating some degree of regression but still showing a marked improvement from the pre-treatment measurements (P < 0.0001). Proportion of Distant Esophoria Changes in the proportion of distant esophoria are shown in Fig. 3 . Before treatment, 222 (97%) patients had distant esotropia, while six (3%) patients had distant esophoria. One month after treatment, the number of patients with distant esotropia had decreased to 66 (30%), whereas that of patients with distant esophoria had increased to 153 (70%) (P < 0.0001). At the final observation, 57 (35%) patients had distant esotropia, and 107 (65%) patients had distant esophoria, showing a significant increase in the proportion of distant esophoria compared with pretreatment (P < 0.0001). Proportion of Near Stereopsis Less than 100 Seconds The proportion of patients with good near stereopsis < 100 arc seconds (arcsec) also showed notable changes (Fig. 4 ). Before treatment, 84 (37%) patients had near stereopsis < 100 arcsec, 68 (30%) patients had near stereopsis ≥ 100 arcsec, and 76 (33%) patients had no stereopsis. One month after treatment, 137 (62%) patients achieved near stereopsis < 100 arcsec, 62 (28%) patients had near stereopsis ≥ 100 arcsec, and 21 (10%) patients had no stereopsis. At the final observation, 124 (75%) patients had near stereopsis < 100 arcsec, 27 (16%) patients had near stereopsis ≥ 100 arcsec, and only 14 (9%) patients had no stereopsis, indicating a significant improvement in near stereopsis over time. The proportion of patients with good near stereopsis significantly increased over time (1 month, P = 0.0005; final observation, P < 0.0001). Adverse Events The presence of adverse events was confirmed in 224 patients, as summarized in Table 3 . The most common adverse event was ptosis, occurring in 53 (24%) patients. Hypertropia was observed in 35 (16%) patients. While not classified as adverse events but rather as intended effects of the drug, overcorrection was noted in 49 (22%) patients and ocular motility dysfunction in 33 (15%) patients. All of these events were transient and improved within approximately 1 month. Table 3 Adverse Events Adverse Event Number of Cases (%) n = 224 Ptosis 53 (24%) Hypertropia 35 (16%) Overcorrection 49 (22%) Ocular Motility Dysfunction 33 (15%) Ptosis was observed in 24% of patients, and hypertropia was observed in 16%. Although overcorrection and ocular motility dysfunction are the intended effects of the drug rather than adverse events, they are included in the same table as they cause discomfort to the patients. Relationship Between Dosage and Adverse Events The relationship between the dosage of BTXA and the occurrence of adverse events was examined. The group that experienced adverse events such as ptosis or hypertropia (n = 78) received a higher average dose of BTXA compared to the group without these adverse events (n = 146). The average dose in the adverse event group was 3.01 ± 0.99 units, while the group without adverse events received 2.60 ± 0.87 units. This difference was statistically significant (P = 0.001). Factors Contributing to Success The analysis suggested that the duration from onset to treatment (P = 0.024) and post-treatment overcorrection (P = 0.001) independently influenced the likelihood of success. Specifically, a shorter duration from onset to treatment and post-treatment overcorrection were associated with higher success rates. The results are summarized in Table 4 . Table 4 Factors Contributing to Success (Multivariable Logistic Regression Analysis) Explanatory Variables Odds Ratio (95% CI) p-value Duration from Onset to Treatment 0.993 (0.987–0.999) 0.024* Dosage 0.774 (0.483–1.242) 0.289 Pre-treatment Angle of deviation 1.023 (0.982–1.066) 0.273 Pre-treatment Near Stereopsis 2.123 (0.959–4.701) 0.064 Post-treatment Overcorrection 5.861 (2.041–16.835) 0.001* Post-treatment Ocular Motility Dysfunction 2.253 (0.630–8.059) 0.212 The analysis suggested that the duration from onset to treatment (P = 0.024) and post-treatment overcorrection (P = 0.001) independently influence the likelihood of success. Discussion This study evaluated the clinical efficacy, safety, and success factors associated with BTXA injections in the treatment of AACE. The results revealed significant improvements in eye alignment and stereopsis with BTXA treatment and identified success factors that contribute to maintaining long-term favorable outcomes beyond the active period of the drug. Although transient adverse events were observed in approximately 20% of the cases, all were temporary and resolved within approximately 1 month. Higher doses of BTXA are associated with an increased incidence of ptosis and hypertropia. Multivariable logistic regression analysis revealed that a shorter time from onset to treatment and post-treatment overcorrection were independent success factors. This finding strongly suggests that early intervention is crucial for achieving success. However, overcorrection can be uncomfortable for patients, making it impractical as an initial goal. A more clinically appropriate approach would be to assess the response after the initial injection and adjust the dosage to suit each patient accordingly. This study represents the largest series of 228 cases involving 318 injections performed by the same surgeon at a single institution to evaluate the outcomes of BTXA injections for strabismus. Both this study and previous studies [9, 10, 12, 14] have shown favorable outcomes with BTXA injections for AACE. With the increasing use of digital devices, the incidence of AACE is also increasing and is becoming a growing concern [2, 6, 15-18] . Unlike surgery, which cannot be performed until the condition stabilizes, BTXA injections can be administered during the acute phase, making them particularly effective in cases of acquired strabismus, such as AACE, where patients complain of diplopia. Additionally, BTXA injections are less invasive than surgery, can be administered quickly during an outpatient visit, and cause minimal subsequent discomfort. Therefore, BTXA injections should be considered as a viable treatment option for AACE. The incidence of complications, such as ptosis and hypertropia, after the injections was consistent with previous reports [19, 20] . Although complications occurred at a certain rate, none were permanent, indicating that BTXA injections are a safe treatment option. This study also suggested that a higher dose is associated with an increased likelihood of complications. Therefore, for cases with larger esotropia angles requiring higher dosages, a more careful pretreatment explanation is necessary. One potential approach to reduce complication rates is to inject into both medial rectus muscles, thereby reducing the dosage per muscle. Although the effects of BTXA typically diminish within 3–4 months, some reports suggest that BTXA injections can cause irreversible changes in muscle fibers, particularly in delicate extraocular muscles [21] . This study revealed that approximately 57% of the patients who received BTXA injections maintained good ocular alignment without diplopia for more than 6 months post-injection. AACE often occurs in patients who initially have a good binocular function and controlled phoria but develop esotropia and notice diplopia at a distance after engaging in excessive near work. Using BTXA injections to induce phoria and adopting lifestyle habits, such as maintaining proper viewing distance from digital devices and reducing screen time, may restore the patient’s ocular alignment to its pre-esotropia state without the need for surgery. The limitations of this study include a high dropout rate (63 out of 228 cases were lost to follow-up 6 months after the initial injection), the retrospective nature of the study leading to potential selection bias, and the fact that the data were derived from a single institution. However, given its large sample size, this study likely plays a meaningful role in assessing the efficacy and safety of BTXA injections for strabismus. Future multi-center, prospective studies will be necessary to further verify the efficacy of BTXA for AACE. Methods Ethic declarations This study was approved by the Japanese Medical Association Ethics Committee (approval no. R5-12) and adhered to the ethical standards outlined in the Declaration of Helsinki. The institutional review board granted the study an informed consent waiver and approved the study protocol. Patients This retrospective, single-center study included patients diagnosed with AACE at the CS Eye Clinic who received their first BTXA injection by the same surgeon between November 2019 and June 2023. Medical records from November 2019 to June 2024 were reviewed. The diagnostic criteria for AACE in this study were partially modified from previous reports [1, 2, 8] and included the following: (1) onset of diplopia or esotropia after growth, (2) no limitation in ocular motility, (3) absence of organic disease on cranial or orbital CT or MRI, (4) no accommodative component, (5) no history of systemic disease or head trauma, (6) no prior ocular issues such as strabismus or amblyopia, and (7) for patients aged 50 and above, no disruption of the Lateral rectus-Superior rectus (LR-SR) band on orbital MRI suggestive Sagging Eye Syndrome. Patients whose exact onset date could not be determined were included, as AACE often develops subacutely or insidiously, according to previous reports [4, 17] and our clinical experience. Patients who showed reduced esotropia with hyperopic glasses or exhibited convergence spasms were excluded. Patient data The following background information of the patients was obtained from their medical records: sex, age at the first injection, and the period from the onset of diplopia to the first injection. We retrospectively examined the number of BTXA injections, dosage, pre- and post-injection distances, eye positions (qualitative and quantitative), near stereopsis, outcomes, and adverse events. For post-injection distant eye position and near stereopsis, measurements were extracted from all available data 1 month after the first injection and from the final observation for cases with a follow-up period of 6 months or longer. In the surgery group shown in the following section, eye position and near stereopsis data were obtained just before surgery. The qualitative distance eye position was assessed using a cover test with a distant target (5 m), whereas the quantitative distance eye position (angle of deviation) was measured using an alternate prism cover test at a distance. Near stereopsis was measured using the Stereo Fly test (Stereo Optical Inc., Chicago, IL, USA) or the Randot Stereo test (Stereo Optical Inc., Chicago, IL, USA). Outcome Definitions Outcomes were evaluated for cases with a follow-up of more than 6 months after the first injection, defined as follows: • Cure: Absence of diplopia or esophoria at a distance in the primary position, sustained for more than 6 months after the last injection. • Improvement: Recognition of diplopia only during fatigue or maintenance of deviation angle ≤ 1/2 of the pre-injection angle at a distance, at more than 6 months follow-up after the last injection. • No change: No change in diplopia or angle of deviation compared to pre-injection at more than 6 months of follow-up after the last injection. • Repeated injections: Less than 6 months have passed since the last injection at the time of the final observation. • Surgery: Esotropia surgery was performed after injection. And "Cure" and "Improvement" were defined as successful outcomes. Statistical analysis Categorical data are summarized as frequencies and percentages, whereas continuous data are summarized as mean ± standard deviation (SD) or median and range (minimum–maximum). A paired t-test was used to evaluate the changes in the distant angle of deviation from pretreatment to 1-month post-injection, as well as from pretreatment to the final observation in cases with a follow-up period of more than 6 months. The McNemar test was used to evaluate the changes in the proportion of distant esophoria and near stereopsis <100 arcsec from pre-treatment to 1-month post-injection, as well as from pre-treatment to the final observation for cases with a follow-up period exceeding 6 months. An independent two-sample t-test was used to compare the BTXA dose between the group that experienced adverse events (ptosis or hypertropia) at least once and the group that did not. To identify the factors contributing to the success of BTXA treatment, multivariable logistic regression analysis was performed. Based on the results of the simple regression analysis and clinically important factors, six explanatory variables were selected: duration from onset to treatment, dosage, pretreatment angle of deviation, pretreatment near stereopsis, posttreatment overcorrection, and posttreatment ocular motility dysfunction. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). All p-values were two-sided. Because this study was exploratory in nature, no adjustments were made to multiple comparisons. Declarations Author Contribution M.U. managed the overall research and drafted the manuscript. T.G. supervised the manuscript writing. A.W., K.F., Y.K., R.Y., and N.T. collected and gathered the data. H.Y. conducted the medical statistics. All authors reviewed the manuscript. Acknowledgement We would like to thank Editage (www.editage.jp) for English language editing. Data Availability The datasets used and analyzed in the study are available from either of the corresponding authors, M. U. or T. G, upon reasonable request" in the manuscript. References Clark, A. C., Nelson, L. B., Simon, J. W., Wagner, R. & Rubin, S. E. Acute acquired comitant esotropia. Br. J. Ophthalmol. 73 , 636-638 (1989). Okita, Y. et al. Yearly changes in cases of acute acquired comitant esotropia during a 12-year period. Graefes Arch. Clin. Exp. Ophthalmol. 261 , 2661-2668 (2023). Kim, J. M., Shin, J., Lee, Y. H. & Lee, Y. H. Clinical features and change in incidence of acute acquired comitant esotropia: a 15-year single-centre study in South Korea. Eye (Lond.) 38 , 1529-1534 (2024). Roda, M. et al. Epidemiology, clinical features, and surgical outcomes of acute acquired concomitant esotropia associated with myopia. PLOS ONE 18 , e0280968 (2023). Iimori, H. et al. Clinical presentations of acquired comitant esotropia in 5-35 years old Japanese and digital device usage: a multicenter registry data analysis study. Jpn. J. Ophthalmol. 67 , 629-636 (2023). Lee, H. S., Park, S. W. & Heo, H. Acute acquired comitant esotropia related to excessive Smartphone use. BMC Ophthalmol. 16 , 37 (2016). Spierer, A. Acute concomitant esotropia of adulthood. Ophthalmology 110 , 1053-1056 (2003). Burian, H. M. & Miller, J. E. Comitant convergent strabismus with acute onset. Am. J. Ophthalmol. 45 , 55-64 (1958). Huang, X. Q. et al. Clinical efficacy of botulinum toxin type A on acute acquired comitant esotropia. Int. J. Ophthalmol. 15 , 1845-1851 (2022). Cheung, C. S. Y. et al. A comparison of Chemodnervation to incisional surgery for acute, acquired, comitant esotropia: an international study. Am. J. Ophthalmol. 263 , 160-167 (2024). Ai, L. et al. Botulinum toxin treatment for bielschowsky acquired commitant esotropia in adults. BMC Ophthalmol. 22 , 395 (2022). Lang, L. J. et al. Comparison of botulinum toxin with surgery for the treatment of acute acquired comitant esotropia and its clinical characteristics. Sci. Rep. 9 , 13869 (2019). Tong, L. et al. Functional acute acquired comitant esotropia: clinical characteristics and efficacy of single botulinum toxin type A injection. BMC Ophthalmol. 20 , 464 (2020). Li, Y. et al. The efficacy of botulinum toxin type A treatment and surgery for acute acquired comitant esotropia. Front. Med. (Lausanne) 10 , 1219419 (2023). Neena, R., Remya, S. & Anantharaman, G. Acute acquired comitant esotropia precipitated by excessive near work during the COVID-19-induced home confinement. Indian J. Ophthalmol. 70 , 1359-1364 (2022). Cai, C., Dai, H. & Shen, Y. Clinical characteristics and surgical outcomes of acute acquired comitant esotropia. BMC Ophthalmol. 19 , 173 (2019). Cai, J. et al. Analysis of independent risk factors for acute acquired comitant esotropia. Int. J. Ophthalmol. 16 , 1854-1859 (2023). Guo, S., Zhou, Y., Xi, S., Zhao, C. & Wen, W. Advances in the diagnosis and treatment of acute acquired comitant esotropia. Int. Ophthalmol. 44 , 315 (2024). Bort-Martí, A. R. et al. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst. Rev. 3 , CD006499 (2023). Binenbaum, G. et al. Botulinum toxin injection for the treatment of strabismus: A report by the American Academy of Ophthalmology. Ophthalmology 128 , 1766-1776 (2021). Li, J., Allende, A., Martin, F. & Fraser, C. L. Histopathological changes of fibrosis in human extra-ocular muscle caused by botulinum toxin A. J. AAPOS 20 , 544-546 (2016). Additional Declarations No competing interests reported. Supplementary Files BTXAACEsubmit.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5596397","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":391912084,"identity":"abbbb606-fba9-4f07-8306-5cac78d13063","order_by":0,"name":"Makiko Ui","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Makiko","middleName":"","lastName":"Ui","suffix":""},{"id":391912085,"identity":"7e8b067e-0775-4792-afe4-df635f83bab3","order_by":1,"name":"Toshiaki Goseki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYJACxgaDBDk2Bh4Yj0gtxqRqYUhIbIBpIQjk3dsfPpxRkJbeJ5F7TIKhxo6BeTYBawzPnDE23GCQk9smkZcmwXAsmYFxzgECWmbksEk+MKgAaskxu8HAdoCBcUYCIS3pz38CtaSzgbX8I0KLvESCGSPQYQlgLYxtRGgx4DljLDnDIM2wjeeN+Y/EvmQegn6Rb29/+LHnT7K8fHuOscGHb3ZyhoRCzADFSKCTeAxn4NfBII9hpLwEAS2jYBSMglEw4gAA2P1BjZO2azwAAAAASUVORK5CYII=","orcid":"","institution":"International University of Health and Welfare, Atami Hospital","correspondingAuthor":true,"prefix":"","firstName":"Toshiaki","middleName":"","lastName":"Goseki","suffix":""},{"id":391912086,"identity":"93b6fc34-60cc-4e96-b5cd-df6f8d0ad30f","order_by":2,"name":"Ayumi Watanabe","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Ayumi","middleName":"","lastName":"Watanabe","suffix":""},{"id":391912087,"identity":"1718617f-1e14-424f-b261-c37f78d9d77c","order_by":3,"name":"Kinue Fueki","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Kinue","middleName":"","lastName":"Fueki","suffix":""},{"id":391912090,"identity":"80546133-d1ef-48a8-8ab0-211b7b36d7cc","order_by":4,"name":"Yuko Komiya","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Yuko","middleName":"","lastName":"Komiya","suffix":""},{"id":391912094,"identity":"571865e9-c437-4077-9a65-c58d3fb1e394","order_by":5,"name":"Risako Yamamoto","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Risako","middleName":"","lastName":"Yamamoto","suffix":""},{"id":391912096,"identity":"db5984bb-2bbb-476c-bc3b-d21dc7d5b959","order_by":6,"name":"Noriko Tsutsumi","email":"","orcid":"","institution":"CS eye clinic","correspondingAuthor":false,"prefix":"","firstName":"Noriko","middleName":"","lastName":"Tsutsumi","suffix":""},{"id":391912098,"identity":"ff98b627-707c-418b-9dde-dc91815c1509","order_by":7,"name":"Hiroki Yoshida","email":"","orcid":"","institution":"Data Seed Inc","correspondingAuthor":false,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Yoshida","suffix":""}],"badges":[],"createdAt":"2024-12-07 01:08:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5596397/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5596397/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72362479,"identity":"07295f73-e202-4204-8350-000096fa5d62","added_by":"auto","created_at":"2024-12-26 06:08:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":554279,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment Outcomes. 94 (57%) patients had successful outcomes. Among these, 76 (46%) patients were cured, while 18 (11%) patients showed improvement.\u003c/p\u003e\n\u003cp\u003eA subset of 40 (24%) patients required repeated injections and surgery was performed in 27 (17%) patients. Four (2%) patients showed no change in their condition for more than six months after the initial injection.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/0c18ad683673429b2954af66.png"},{"id":72362484,"identity":"bd8204e7-8cee-4c18-8c30-cc23fd82ecb5","added_by":"auto","created_at":"2024-12-26 06:08:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":34826,"visible":true,"origin":"","legend":"\u003cp\u003eThe mean pre-treatment angle of deviation was 28.6 ± 12.0 PD. One month after treatment, it significantly decreased to 2.3 ± 12.9 PD (P\u0026lt;0.0001). At the final observation, the angle of deviation slightly increased to 10.2 ± 11.4 PD, showing significant improvement compared to the pre-treatment angle (P\u0026lt;0.0001).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/43d433a4982fd1e7e6cb83bf.png"},{"id":72362481,"identity":"595e3e61-a766-4ffb-804e-25e6b5f1b20a","added_by":"auto","created_at":"2024-12-26 06:08:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37128,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of distant esophoria. Before treatment, six (3%) patients had distant esophoria. One month after treatment, the number of patients with distant esophoria increased to 153 (70%) (P\u0026lt;0.0001). At the final observation, 107 (65%) patients had distant esophoria, showing a significant increase in the proportion of distant esophoria compared to pre-treatment (P\u0026lt;0.0001).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/f6859a7ada2bd6b3b1dbad8f.png"},{"id":72362498,"identity":"7dba2354-9e4c-428b-9b29-a840dc655676","added_by":"auto","created_at":"2024-12-26 06:08:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":36805,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of near stereopsis \u0026lt; 100 arcsec. Before treatment, 84 (37%) patients had near stereopsis \u0026lt; 100 arcsec. One month after the treatment, 137 (62%) patients achieved near stereopsis \u0026lt; 100 arcsec. At the final observation, 124 (75%) patients had near stereopsis \u0026lt; 100 arcsec, demonstrating a significant increase in the proportion of patients with good near stereopsis over time (at 1 month, P=0.0005; at the final observation, P\u0026lt;0.0001).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/784276b322145d40c2e703f5.png"},{"id":76171588,"identity":"c4a7250d-8efa-472d-928d-6a2342349c98","added_by":"auto","created_at":"2025-02-13 05:34:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1526576,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/8b747534-4d3c-4938-9f21-b93dc2c76112.pdf"},{"id":72362482,"identity":"0e1db529-1b7e-43da-8164-71d8d24e31e6","added_by":"auto","created_at":"2024-12-26 06:08:53","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":37140,"visible":true,"origin":"","legend":"","description":"","filename":"BTXAACEsubmit.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5596397/v1/41ce9efd4c9f12e735b6c4a7.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Efficacy, Safety, and Success Factors of Botulinum Toxin Type A in the Treatment of Acute Acquired Comitant Esotropia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute acquired comitant esotropia (AACE) is a rare form of esotropia\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. However, there has been a notable increase in reported cases in recent years, likely due to the rising use of digital devices, such as smartphones\u003csup\u003e[\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. AACE typically manifests as late-onset esotropia with diplopia in individuals with normal binocular vision\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Unlike other forms of esotropia that usually appear in early childhood or are associated with significant hyperopic refractive errors or neurological issues, AACE typically occurs in older children and adults. It is characterized by late-onset esotropia with diplopia, consistent esotropia across all gaze directions, minimal or no significant hyperopia, and the absence of organic diseases such as brain tumors\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Neurological examinations and imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRIs), generally return normal results, distinguishing AACE from other causes of acute-onset esotropia.\u003c/p\u003e \u003cp\u003eIn recent years, Botulinum toxin type A (BTXA) injections have emerged as a less invasive alternative to traditional strabismus surgery\u003csup\u003e[\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. BTXA temporarily paralyzes the overactive medial rectus muscles, allowing the eyes to realign. Studies have demonstrated that BTXA can effectively reduce esotropia and improve binocular function with a relatively low risk of complications. In some cases, the effects of BTXA extend beyond the drug's active period, leading to long-term alignment. However, it remains unclear which specific cases result in long-term success. Moreover, few large-scale studies have reported these outcomes.\u003c/p\u003e \u003cp\u003eThis study aims to investigate the efficacy and safety of BTXA injections in treating AACE while also identifying factors that contribute to successful treatment outcomes.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Demographics\u003c/h2\u003e \u003cp\u003eThe study included 228 patients diagnosed with AACE who received their first BTXA injection at the CS Eye Clinic by the same surgeon. The patient demographics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of included patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll (n\u0026thinsp;=\u0026thinsp;228)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Median (min\u0026ndash;max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (12\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex (male)\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (41%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration from onset to treatment (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.8\u0026thinsp;\u0026plusmn;\u0026thinsp;163.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Median (min\u0026ndash;max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.5 (0.2\u0026ndash;486.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistant Angle of Deviation (PD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Median (min\u0026ndash;max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (4\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistant Qualitative Eye Position\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Esotropia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222 (97%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Esophoria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNear Stereopsis\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Absent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152 (67%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObservation Period (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1 \u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- Median (min\u0026ndash;max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7 (0.0\u0026ndash;36.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe patients\u0026rsquo; ages ranged from 12 to 75 years, with a mean age of 30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 years. The minimum age of 12 years was chosen because, in Japan, public health insurance covers BTXA treatment for strabismus only for patients aged\u0026thinsp;\u0026ge;\u0026thinsp;12 years. The study population comprised 93 (41%) males and 135 (59%) females. The duration from symptom onset to the initiation of BTXA treatment varied significantly, with a median time to treatment of 36.5 months (range: 0.2\u0026ndash;486.7 months). The mean angle of esotropia at a distance was 28.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 prism diopters (PD). Most patients (97%) exhibited stable esotropia at distance, while a small proportion (3%) had esophoria at distance. Near stereopsis was absent in 76 (33%) patients and present in 152 (67%) patients. The mean observation period was 9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 months.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInjection Details\u003c/h3\u003e\n\u003cp\u003eA total of 318 BTXA injections were administered, with an average of 1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 injections per patient. The average dosage per injection was 2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 units (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInjection Details\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjection Details\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll (n\u0026thinsp;=\u0026thinsp;318)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of Injections (times per patient)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDosage (units per injection)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe total number of injections was 318, with an average of 1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 injections per patient. The average dosage per injection was 2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 units.\u003c/p\u003e\n\u003ch3\u003eTreatment Outcomes\u003c/h3\u003e\n\u003cp\u003eThe treatment outcomes of the 165 patients who were observed for more than 6 months after the initial injection are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Overall, 94 (57%) patients achieved successful outcomes. Among these, 76 (46%) patients were cured and 18 (11%) patients showed improvement.\u003c/p\u003e \u003cp\u003eA subset of 40 (24%) patients required repeated injections because of esotropia recurrence. Surgery was performed in 27 (17%) patients who did not opt for additional BTXA injections owing to recurrence, inadequate response, or adverse events. Four (2%) patients showed no change in their condition for more than 6 months after the initial injection.\u003c/p\u003e\n\u003ch3\u003eChanges in Distant Angle of Deviation\u003c/h3\u003e\n\u003cp\u003eThe changes in the distance angle of deviation over time are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Before the treatment, the mean angle of deviation was 28.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0 PD. One month after treatment, this angle significantly reduced to 2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9 PD (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). At the final observation, the mean angle of deviation slightly increased to 10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4 PD, indicating some degree of regression but still showing a marked improvement from the pre-treatment measurements (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\n\u003ch3\u003eProportion of Distant Esophoria\u003c/h3\u003e\n\u003cp\u003eChanges in the proportion of distant esophoria are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Before treatment, 222 (97%) patients had distant esotropia, while six (3%) patients had distant esophoria. One month after treatment, the number of patients with distant esotropia had decreased to 66 (30%), whereas that of patients with distant esophoria had increased to 153 (70%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). At the final observation, 57 (35%) patients had distant esotropia, and 107 (65%) patients had distant esophoria, showing a significant increase in the proportion of distant esophoria compared with pretreatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eProportion of Near Stereopsis Less than 100 Seconds\u003c/h2\u003e \u003cp\u003eThe proportion of patients with good near stereopsis\u0026thinsp;\u0026lt;\u0026thinsp;100 arc seconds (arcsec) also showed notable changes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Before treatment, 84 (37%) patients had near stereopsis\u0026thinsp;\u0026lt;\u0026thinsp;100 arcsec, 68 (30%) patients had near stereopsis\u0026thinsp;\u0026ge;\u0026thinsp;100 arcsec, and 76 (33%) patients had no stereopsis. One month after treatment, 137 (62%) patients achieved near stereopsis\u0026thinsp;\u0026lt;\u0026thinsp;100 arcsec, 62 (28%) patients had near stereopsis\u0026thinsp;\u0026ge;\u0026thinsp;100 arcsec, and 21 (10%) patients had no stereopsis. At the final observation, 124 (75%) patients had near stereopsis\u0026thinsp;\u0026lt;\u0026thinsp;100 arcsec, 27 (16%) patients had near stereopsis\u0026thinsp;\u0026ge;\u0026thinsp;100 arcsec, and only 14 (9%) patients had no stereopsis, indicating a significant improvement in near stereopsis over time. The proportion of patients with good near stereopsis significantly increased over time (1 month, P\u0026thinsp;=\u0026thinsp;0.0005; final observation, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAdverse Events\u003c/h3\u003e\n\u003cp\u003eThe presence of adverse events was confirmed in 224 patients, as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The most common adverse event was ptosis, occurring in 53 (24%) patients. Hypertropia was observed in 35 (16%) patients. While not classified as adverse events but rather as intended effects of the drug, overcorrection was noted in 49 (22%) patients and ocular motility dysfunction in 33 (15%) patients. All of these events were transient and improved within approximately 1 month.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse Events\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse Event\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Cases (%) n\u0026thinsp;=\u0026thinsp;224\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePtosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertropia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvercorrection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular Motility Dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePtosis was observed in 24% of patients, and hypertropia was observed in 16%. Although overcorrection and ocular motility dysfunction are the intended effects of the drug rather than adverse events, they are included in the same table as they cause discomfort to the patients.\u003c/p\u003e\n\u003ch3\u003eRelationship Between Dosage and Adverse Events\u003c/h3\u003e\n\u003cp\u003eThe relationship between the dosage of BTXA and the occurrence of adverse events was examined. The group that experienced adverse events such as ptosis or hypertropia (n\u0026thinsp;=\u0026thinsp;78) received a higher average dose of BTXA compared to the group without these adverse events (n\u0026thinsp;=\u0026thinsp;146). The average dose in the adverse event group was 3.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99 units, while the group without adverse events received 2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 units. This difference was statistically significant (P\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFactors Contributing to Success\u003c/h2\u003e \u003cp\u003eThe analysis suggested that the duration from onset to treatment (P\u0026thinsp;=\u0026thinsp;0.024) and post-treatment overcorrection (P\u0026thinsp;=\u0026thinsp;0.001) independently influenced the likelihood of success. Specifically, a shorter duration from onset to treatment and post-treatment overcorrection were associated with higher success rates. The results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors Contributing to Success (Multivariable Logistic Regression Analysis)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExplanatory Variables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration from Onset to Treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.993 (0.987\u0026ndash;0.999)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.024*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDosage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.774 (0.483\u0026ndash;1.242)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-treatment Angle of deviation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.023 (0.982\u0026ndash;1.066)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-treatment Near Stereopsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.123 (0.959\u0026ndash;4.701)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment Overcorrection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.861 (2.041\u0026ndash;16.835)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment Ocular Motility Dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.253 (0.630\u0026ndash;8.059)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe analysis suggested that the duration from onset to treatment (P\u0026thinsp;=\u0026thinsp;0.024) and post-treatment overcorrection (P\u0026thinsp;=\u0026thinsp;0.001) independently influence the likelihood of success.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated the clinical efficacy, safety, and success factors associated with BTXA injections in the treatment of AACE. The results revealed significant improvements in eye alignment and stereopsis with BTXA treatment and identified success factors that contribute to maintaining long-term favorable outcomes beyond the active period of the drug. Although transient adverse events were observed in approximately 20% of the cases, all were temporary and resolved within approximately 1 month. Higher doses of BTXA are associated with an increased incidence of ptosis and hypertropia. Multivariable logistic regression analysis revealed that a shorter time from onset to treatment and post-treatment overcorrection were independent success factors. This finding strongly suggests that early intervention is crucial for achieving success. However, overcorrection can be uncomfortable for patients, making it impractical as an initial goal. A more clinically appropriate approach would be to assess the response after the initial injection and adjust the dosage to suit each patient accordingly.\u003c/p\u003e\n\u003cp\u003eThis study represents the largest series of 228 cases involving 318 injections performed by the same surgeon at a single institution to evaluate the outcomes of BTXA injections for strabismus. Both this study and previous studies\u003csup\u003e[9, 10, 12, 14]\u003c/sup\u003e have shown favorable outcomes with BTXA injections for AACE. With the increasing use of digital devices, the incidence of AACE is also increasing and is becoming a growing concern\u003csup\u003e[2, 6, 15-18]\u003c/sup\u003e. Unlike surgery, which cannot be performed until the condition stabilizes, BTXA injections can be administered during the acute phase, making them particularly effective in cases of acquired strabismus, such as AACE, where patients complain of diplopia. Additionally, BTXA injections are less invasive than surgery, can be administered quickly during an outpatient visit, and cause minimal subsequent discomfort. Therefore, BTXA injections should be considered as a viable treatment option for AACE.\u003c/p\u003e\n\u003cp\u003eThe incidence of complications, such as ptosis and hypertropia, after the injections was consistent with previous reports\u003csup\u003e[19, 20]\u003c/sup\u003e. Although complications occurred at a certain rate, none were permanent, indicating that BTXA injections are a safe treatment option. This study also suggested that a higher dose is associated with an increased likelihood of complications. Therefore, for cases with larger esotropia angles requiring higher dosages, a more careful pretreatment explanation is necessary. One potential approach to reduce complication rates is to inject into both medial rectus muscles, thereby reducing the dosage per muscle.\u003c/p\u003e\n\u003cp\u003eAlthough the effects of BTXA typically diminish within 3–4 months, some reports suggest that BTXA injections can cause irreversible changes in muscle fibers, particularly in delicate extraocular muscles \u003csup\u003e[21]\u003c/sup\u003e. This study revealed that approximately 57% of the patients who received BTXA injections maintained good ocular alignment without diplopia for more than 6 months post-injection. AACE often occurs in patients who initially have a good binocular function and controlled phoria but develop esotropia and notice diplopia at a distance after engaging in excessive near work. Using BTXA injections to induce phoria and adopting lifestyle habits, such as maintaining proper viewing distance from digital devices and reducing screen time, may restore the patient’s ocular alignment to its pre-esotropia state without the need for surgery.\u003c/p\u003e\n\u003cp\u003eThe limitations of this study include a high dropout rate (63 out of 228 cases were lost to follow-up 6 months after the initial injection), the retrospective nature of the study leading to potential selection bias, and the fact that the data were derived from a single institution. However, given its large sample size, this study likely plays a meaningful role in assessing the efficacy and safety of BTXA injections for strabismus. Future multi-center, prospective studies will be necessary to further verify the efficacy of BTXA for AACE.\u003c/p\u003e\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eEthic declarations\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis study was approved by the Japanese Medical Association Ethics Committee (approval no. R5-12) and adhered to the ethical standards outlined in the Declaration of Helsinki. The institutional review board granted the study an informed consent waiver and approved the study protocol.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis retrospective, single-center study included patients diagnosed with AACE at the CS Eye Clinic who received their first BTXA injection by the same surgeon between November 2019 and June 2023. Medical records from November 2019 to June 2024 were reviewed.\u003c/p\u003e\u003cp\u003eThe diagnostic criteria for AACE in this study were partially modified from previous reports\u003csup\u003e[1, 2, 8]\u003c/sup\u003e and included the following: (1) onset of diplopia or esotropia after growth, (2) no limitation in ocular motility, (3) absence of organic disease on cranial or orbital CT or MRI, (4) no accommodative component, (5) no history of systemic disease or head trauma, (6) no prior ocular issues such as strabismus or amblyopia, and (7) for patients aged 50 and above, no disruption of the Lateral rectus-Superior rectus (LR-SR) band on orbital MRI suggestive Sagging Eye Syndrome. Patients whose exact onset date could not be determined were included, as AACE often develops subacutely or insidiously, according to previous reports\u003csup\u003e[4, 17]\u003c/sup\u003e and our clinical experience. Patients who showed reduced esotropia with hyperopic glasses or exhibited convergence spasms were excluded.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePatient data\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThe following background information of the patients was obtained from their medical records: sex, age at the first injection, and the period from the onset of diplopia to the first injection. We retrospectively examined the number of BTXA injections, dosage, pre- and post-injection distances, eye positions (qualitative and quantitative), near stereopsis, outcomes, and adverse events. For post-injection distant eye position and near stereopsis, measurements were extracted from all available data 1 month after the first injection and from the final observation for cases with a follow-up period of 6 months or longer. In the surgery group shown in the following section, eye position and near stereopsis data were obtained just before surgery. The qualitative distance eye position was assessed using a cover test with a distant target (5 m), whereas the quantitative distance eye position (angle of deviation) was measured using an alternate prism cover test at a distance. Near stereopsis was measured using the Stereo Fly test (Stereo Optical Inc., Chicago, IL, USA) or the Randot Stereo test (Stereo Optical Inc., Chicago, IL, USA).\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eOutcome Definitions\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eOutcomes were evaluated for cases with a follow-up of more than 6 months after the first injection, defined as follows:\u003c/p\u003e\u003cp\u003e• Cure: Absence of diplopia or esophoria at a distance in the primary position, sustained for more than 6 months after the last injection.\u003c/p\u003e\u003cp\u003e• Improvement: Recognition of diplopia only during fatigue or maintenance of deviation angle ≤ 1/2 of the pre-injection angle at a distance, at more than 6 months follow-up after the last injection.\u003c/p\u003e\u003cp\u003e• No change: No change in diplopia or angle of deviation compared to pre-injection at more than 6 months of follow-up after the last injection.\u003c/p\u003e\u003cp\u003e• Repeated injections: Less than 6 months have passed since the last injection at the time of the final observation.\u003c/p\u003e\u003cp\u003e• Surgery: Esotropia surgery was performed after injection.\u003c/p\u003e\u003cp\u003eAnd \"Cure\" and \"Improvement\" were defined as successful outcomes.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eCategorical data are summarized as frequencies and percentages, whereas continuous data are summarized as mean ± standard deviation (SD) or median and range (minimum–maximum). A paired t-test was used to evaluate the changes in the distant angle of deviation from pretreatment to 1-month post-injection, as well as from pretreatment to the final observation in cases with a follow-up period of more than 6 months. The McNemar test was used to evaluate the changes in the proportion of distant esophoria and near stereopsis \u0026lt;100 arcsec from pre-treatment to 1-month post-injection, as well as from pre-treatment to the final observation for cases with a follow-up period exceeding 6 months. An independent two-sample t-test was used to compare the BTXA dose between the group that experienced adverse events (ptosis or hypertropia) at least once and the group that did not. To identify the factors contributing to the success of BTXA treatment, multivariable logistic regression analysis was performed. Based on the results of the simple regression analysis and clinically important factors, six explanatory variables were selected: duration from onset to treatment, dosage, pretreatment angle of deviation, pretreatment near stereopsis, posttreatment overcorrection, and posttreatment ocular motility dysfunction. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). All p-values were two-sided. Because this study was exploratory in nature, no adjustments were made to multiple comparisons.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.U. managed the overall research and drafted the manuscript. T.G. supervised the manuscript writing. A.W., K.F., Y.K., R.Y., and N.T. collected and gathered the data. H.Y. conducted the medical statistics. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed in the study are available from either of the corresponding authors, M. U. or T. G, upon reasonable request\" in the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eClark, A. C., Nelson, L. B., Simon, J. W., Wagner, R. \u0026amp; Rubin, S. E. Acute acquired comitant esotropia. \u003cem\u003eBr. J. Ophthalmol.\u003c/em\u003e \u003cstrong\u003e73\u003c/strong\u003e, 636-638 (1989).\u003c/li\u003e\n\u003cli\u003eOkita, Y.\u003cem\u003e et al.\u003c/em\u003e Yearly changes in cases of acute acquired comitant esotropia during a 12-year period. \u003cem\u003eGraefes Arch. Clin. Exp. 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AAPOS\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 544-546 (2016).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute acquired comitant esotropia (AACE), Botulinum toxin type A (BTXA), Strabismus, Diplopia, Eye alignment, Stereopsis, Success rate, Success factors","lastPublishedDoi":"10.21203/rs.3.rs-5596397/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5596397/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAcute acquired comitant esotropia (AACE) is an increasingly reported form of esotropia, possibly linked to the rising use of digital devices. Botulinum toxin type A (BTXA) has emerged as a minimally invasive treatment alternative to surgery, particularly for patients who present with diplopia. This study retrospectively evaluated 228 patients with AACE who received BTXA injections at a single center. Treatment outcomes, adverse events, and factors influencing success were analyzed. The average patient age was 30.9 years, and 57% achieved successful outcomes, with 46% being cured and 11% showing improvement. Transient adverse events, including ptosis (24%) and hypertropia (16%), were observed. The study found that shorter duration from onset to treatment (P\u0026thinsp;=\u0026thinsp;0.024) and post-treatment overcorrection (P\u0026thinsp;=\u0026thinsp;0.001) were associated with higher success rates. Although some patients required additional treatments or surgery due to recurrence, BTXA proved to be an effective intervention for AACE, with a significant improvement in eye alignment and stereopsis. These findings suggest that early intervention with BTXA is crucial for successful outcomes and offers a safe, less invasive alternative to traditional strabismus surgery.\u003c/p\u003e","manuscriptTitle":"Clinical Efficacy, Safety, and Success Factors of Botulinum Toxin Type A in the Treatment of Acute Acquired Comitant Esotropia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-26 06:08:25","doi":"10.21203/rs.3.rs-5596397/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2262d299-77c1-4f73-8643-f36d6a0260f3","owner":[],"postedDate":"December 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41774981,"name":"Health sciences/Medical research"},{"id":41774982,"name":"Health sciences/Medical research/Outcomes research"}],"tags":[],"updatedAt":"2025-02-13T05:25:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-26 06:08:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5596397","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5596397","identity":"rs-5596397","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}