AACE occurs in older children and young adults; it is characterized by the sudden onset of diplopia and large-angle esotropia, usually preceded by intermittent diplopia, in a previously orthotropic individual (1). According to Burian and Miller (3), AACE can be divided into 3 distinct categories: type 1 (Swan type) refers to esotropia after the interruption of fusion by a period of monocular occlusion or vision loss; type 2 (Burian-Franceschetti type), often accompanied by mild hypermetropia and minimal accommodation, has no obvious underlying cause other than physical or psychological stress; and type 3 (Bielschowsky type) is characterized by uncorrected myopia of ≥ -5.00 diopters.
However, this historical classification of AACE depends on presumed etiology; it is based on weak evidence. Subsequent studies have shown that most AACE patients do not fit into this classification. Buch et al (4). studied AACE in 48 children aged 1–15 years; 3 patients had type 1 AACE, whereas 9 patients had type 2 AACE. The other patients did not exhibit clinical features matching any of the 3 established categories. In that study, the 3 patients with type 1 AACE clearly had a monocular occlusion event, but the 9 patients with type 2 AACE lacked an obvious etiological event. The authors speculated that esotropia was caused by physical or mental stress in patients without an obvious etiological event. In the study by Ruatta and Schiavi (6), all 26 AACE patients were myopic, but the onset of esotropia occurred while the patients were wearing full correction glasses; thus, AACE in these patients did not fulfill the criteria for type 3. Meng et al (5). studied the clinical features of 51 AACE patients and found that none exhibited AACE matching any classic type. No patients in our study exhibited clinical features matching any classic types of AACE. No patients had a history of ocular injury, monocular vision loss, or occlusion; moreover, no patients admitted to emotional trauma or psychological stress. Although 13 of our patients had myopia > -5.00 diopters, all myopic patients had been wearing appropriate glasses for many years.
An absence of uniform diagnostic criteria is the other problem involved in defining this disease entity. Burian et al. and many subsequent investigators have defined AACE as acute esotropia with diplopia in older children and early adulthood (1, 3, 7, 8). However, the patient groups were heterogenous in many previous studies regarding AACE. Spierer et al (9). analyzed patients aged ≥ 16 years, including patients who did not report diplopia. Chen et al (10). analyzed patients aged ≥ 5 years, but only included patients who reported persistent diplopia. Lee et al (11). studied AACE in children and adolescents aged 1–16 years, including patients who did not report acute diplopia. Importantly, patients with basic esotropia may be included in studies of AACE if researchers include young children (aged < 6 years) who do not report acute diplopia. According to von Noorden (12), basic esotropia is a disease occurring from the age of 6 months into childhood, which does not involve diplopia. By definition, AACE involves a sudden onset of diplopia and constitutes a disease of older children or adults. Although it is unclear whether basic esotropia and AACE are distinct entities, we excluded young children from the present study to narrow the scope of diagnosis. There is a need for discussion to build consensus regarding the definition of AACE.
In this study, we strove to exclude patients with potentially similar diseases. To exclude basic esotropia and to collect reliable information regarding diplopia history, the inclusion age was set at ≥ 8 years. To avoid the involvement of divergence insufficiency or sagging eye syndrome that occurs among older adults, only patients aged < 50 years were included. To exclude incomitant esotropia (e.g., paralytic or restrictive esotropia), only patients with comitant esotropia involving a difference in deviation of ≤ 5 PD between the primary and side gazes were selected. To exclude divergence insufficiency or bilateral 6th nerve palsy, only patients with a difference of ≤ 10 PD between the distant and near deviation angles were selected. To exclude esotropia related to high myopia or accommodative convergence, only patients with refractive errors of -6.0 diopters to + 3.0 diopters were included. Finally, patients with known neurological abnormalities related to paralytic strabismus were excluded.
Chen et al (10). reported that the mean age (± standard deviation) at presentation of 47 AACE patients was 26.6 ± 12.2 years, although their patients were selected without an age limit. Fu et al (13). reported an age range of 3–62 years, with a mean age (± standard deviation) of 23.1 ± 11.7 years. In their study, 6 patients (8.7%), 23 patients (33.3%), and 40 patients (58.0%) presented for initial treatment at the ages of < 10 years, 10–18 years, and > 18 years, respectively. The epidemiological age distribution in our study was similar to the distributions in previous studies (10, 13). AACE is most prevalent in adolescents and young adults.
AACE is suspected to constitute a manifestation of serious neurological disease (14–18). In our study, we recommended brain MRI for selected patients who developed abrupt esotropia, as well as patients who had any symptoms and signs that suggested intracranial abnormalities (e.g., headache, dizziness, tinnitus, or nystagmus). Among the 59 patients in this study, 26 (44.1%) underwent brain MRI, and the other patients attended ≥ 6 months of follow-up. No patients had a relevant abnormality on brain MRI. Ali et al (7). and Song et al (19). also found no relevant neurological abnormalities on brain MRI in their AACE patients. Therefore, we presume that it is better to selectively recommend neuroimaging in patients with AACE, considering the high cost and lack of positive results.
Because this retrospective study was conducted at a single institution (CNUH), we could not determine the incidence of AACE. The proportion of AACE was used as a surrogate indicator to estimate the incidence. CNUH is the only tertiary referral center in a metropolitan area with a population of approximately 1.5 million. The corresponding author was the only specialist with a continuous practice during the study period, and there was no change in the referral system in this area during the study period. Therefore, we presume that the increased proportion of AACE among new patients reflects an increased incidence of AACE. We compared the number of AACE patients with the number of IXT patients because IXT is the most common type of strabismus in South Korea. The proportion of IXT patients did not significantly change during the study period, which suggests that there was no significant change in the referral pattern for strabismus patients in this area. In contrast, the ratio of AACE patients to IXT patients significantly increased, reinforcing our suspicion that the incidence of AACE is increasing in South Korea.
In the past century, most studies of AACE have constituted small case series with ≤ 12 patients (1, 9, 20). However, recently, some studies with large numbers of AACE patients have been reported from East Asia, South Asia, Europe, and the Middle East (5, 6, 13). Thus, the change in incidence appears to be a worldwide phenomenon.
Many authors suspect that excessive near vision work (caused by the use of smartphones or digital devices) is related to the increasing incidence of AACE (11, 19, 21, 22). Some authors have reported that the cessation of smartphone use can decrease the degree of esodeviation in affected patients (11, 22). We also suspect that overuse of smartphones and excessive near vision work are contributing factors. All patients in our study were smartphone users. In recent years, the use of smartphones has led to substantial changes in the daily lives and visual environments of older children and young adults. To our knowledge, no other factors have had greater effects on the visual environments of people worldwide.
The timing of the sharp increase in the incidence of AACE may be related to the presence of additional evidence. The timing of this increase was concordant with the sudden popularity of smartphone use among young people in South Korea. In our study, the incidence of AACE increased sharply beginning in 2013 (Table 2). Since the release of the Galaxy S2 (Samsung Electronics, Suwon, S. Korea) in 2011, the popularization of smartphones in South Korea has accelerated; smartphone use has also rapidly spread among teenagers (23). By the end of 2013, 80% of adolescents were using smartphones, compared with 36.2% in 2011 (24).
Notably, all patients in our study were myopic (Table 1), similar to the patients in other AACE studies (9, 13). In a recently published study involving 51 AACE patients (5), 42 patients were myopic. Limori et al (25). suggested that excessive work with near vision is not the single cause of AACE; they presumed that myopia constitutes an important factor. However, in a study of 15 AACE patients, Neena et al (21). found that only 33.3% had myopia. There is a need for research regarding the association between the development of AACE and the presence of myopia.
Important limitations of this study were that it used a retrospective design and was conducted in a single center. However, to our knowledge, it is the first study to explore changes in the incidence of AACE. A sudden change in the incidence of any disease may have serious implications for public health. Large-scale studies are needed to fully define the incidence and pathophysiology of AACE. We hope this study will attract additional interest from researchers and public health providers, leading to further studies that generate conclusive evidence.