Risk factors associated to amblyopia in children: a case-control study

Amblyopia, also known as “lazy eye”, is a common neurodevelopmental abnormality that results in physiological alterations in the visual pathways and impaired vision in one eye, also called unilateral, less commonly in both. These clinical abnormalities can occur when normal visual development is disrupted early in life, typically before the age of 7 years [1, 2]. Amblyopia causes myriad perceptual deficits in vision, including a loss of visual acuity, position acuity, depth perception, and contrast sensitivity, as well as increased internal noise and problems related to eye movements. Beyond the perceptual deficits are a range of visuomotor deficits and potential psychological sequelae [2].

Aside from refractive error, amblyopia is the most common cause of vision impairment in children and young adults. It has been estimated that amblyopia cases are on the rise, and its global prevalence is predicted to increase by more than two times by 2040 [3—5]. Thus, public health strategies of early screening, treatment, and management are essential. Different studies showed variations in the prevalence of amblyopia in different regions and ages of the populations studied. While the prevalence of amblyopia has decreased in developed countries [6, 7], developing countries have seen high rates [8].

In recent years, there has been a growing interest in identifying the risk factors associated with the development of amblyopia in children. Mainly, because that early detection and treatment of amblyopia can significantly improve visual outcomes and partly because of the potential impact of these risk factors on public health policy and prevention strategies. Common amblyopia risk factors include anisometropic or high refractive error (hyperopia, astigmatism, and myopia), strabismus, cataracts, and ptosis. However, the prevalence of amblyopia risk factors reported in the literature varies by method, region where the study was performed, and age group studied [6—8].

Various predisposing risk factors for amblyopia have been documented, which can be divided into ocular and non-ocular risk factors. The ocular risk factors associated with amblyopia include anisometropic or high refractive error, strabismus, cataract, congenital nasolacrimal duct obstruction, and ptosis [9, 10]. Common non-ocular risk factors associated with amblyopia were mainly identified as perinatal factors, such as prematurity, APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) score, maternal smoking during pregnancy, neonatal intensive care unit hospitalization, and breastfeeding [11]. While the main risk factors have been determined, the association with amblyopia can differ among different studies [12—15]. Thus, an important question is whether different causative factors such as different early visual experiences are closely related to amblyopia in a specific population.

This study aimed to identify ocular and non-ocular risk factors associated with amblyopia in children undergoing routine ophthalmologic evaluation, and to assess the strength of their association with the condition.

We performed a case control study of patients with amblyopia aged 3—14 between January 2019 and December 2020 in the ophthalmology department. The patients were identified using the Clinical Practice Guide: Detection, Diagnosis, Treatment, and Control of refractive errors for CIE 10: H53.0 (Peruvian Ministerial Order N° 648-2014), and a manual review of patient records was performed to confirm the diagnosis of amblyopia.

Patients were enrolled when amblyopia was diagnosed in the medical record. Best-corrected visual acuity measures were obtained using Snellen or Snellen E chart optotypes appropriate to the patient’s age and ability. Stereopsis measurements were obtained using the Titmus stereo acuity test. Exclusion criteria were any ocular deformity such as ptosis or keratopathy which could affect refractive errors, leucoma, congenital glaucoma, congenital cataract, keratoconus malformations, intraocular surgical interventions, abnormalities of the optic nerve, and absence of any ocular disease other than refractive errors and/or congenital syndromes.

Age-matched children without amblyopia were included as the control group, randomly selected from patients who visited the outpatient clinic of the Instituto Regional de Oftalmología (IRO) for routine eye examinations.

Data were collected on sociodemographic and clinical characteristics, including the patient’s gestational age, gender, age at diagnosis, socioeconomic status, and comorbidities. They were collected from Instituto Nacional de Estadística e Informatica (INEI) and clinical history.

For statistical analysis, SPSS ver. 26.0 software (IBM Corporation, Armonk, NY, USA) was used. Comparison between patients with amblyopia versus (vs.) controls was assessed using the independent t-test for continuous variables and chi-square test for categorical variables, as applicable. Bivariate logistic regression was performed regrading amblyopia as the dependent variable to evaluate the relationship between related variables. A p-value <0.05 was considered statistically significant. Data are presented as mean±standard deviation unless stated otherwise.

This study was prospectively approved by IRO and Universidad Privada Antenor Orrego (UPAO) Institutional Review Boards and adhered to the tenets of the Declaration of Helsinki. The IRO and UPAO waived the need for informed consent in the study as all patient records were provided to/accessed by the authors in a fully anonymized format and involved no risk to subjects.

This study evaluated 62 patients with amblyopia and 186 age-matched controls. The mean age of amblyopia patients and controls at the diagnoses was not significantly different (8.32±3.43 vs. 8.01±3.54 years, respectively; p=0.54). Age was divided into groups at 5-year intervals to estimate age-specific prevalence rate (Table 1). Together, 48/62 (77.4%) of the amblyopic children fall into groups of 6—10 and 11—15 years, while only 14/62 (22.6%) had ages of 3 to 5 years. The control group children showed the same tendency related to age; most children had ages over five years. Socioeconomic status upper middle or middle was the dominant (63.3%) in the studied population, followed by lower middle (25.4%) and upper lower (11.3%), with no significant differences between amblyopic and non-amblyopic children (controls) (p=0.587) (see Table 1).

Table 1. Demographics characteristics of the studied population

Overall, 13 of 248 (5.2%) children had astigmatism, 9 (3.6%) had hyperopia, 65 (26.2%) had strabismus, and 7 (2.8%) had myopia. Thirty-five (14.1%) children were found with a combination of myopia and astigmatism, and 80 (32.3%) had a combination of hyperopia and astigmatism. A statistically significant difference was seen in astigmatism (p=0.014), hyperopia (p=0.031), and strabismus (p=0.04) between amblyopic and non-amblyopic children. On the other hand, no statistical significance was identified in the myopia difference (p=0.507). The combination of astigmatism with myopia or hyperopia was more frequent in amblyopic children than controls, with a significance of p=0.027 and p=00001, respectively (Table 2).

Table 2. Ocular conditions in amblyopia patients and age-matched controls

Amblyopia in this population was associated with astigmatism (OR, 3.818; 95% CI 1.13 to 12.10), hyperopia (OR, 3.99; 95% CI 1.14 to 13.27), strabismus (OR, 2.466; 95% CI 1.34 to 4.44). We also found strong associations when astigmatism appears in combination with hyperopia (OR, 4.062; 95% CI 2.21 to 7.30). Although higher odds were demonstrated with ocular conditions, amblyopia was not associated with those evaluated, including prematurity (OR, 0.96; 95% CI, 0.54 to 1.17), gender (OR, 0.85; 95% CI, 0.38 to 1.89) or socioeconomic status (OR, 0.57; 95% CI, 0.20—1.69) (Table 3).

Table 3. Ocular conditions associated with amblyopia in studied population

This study reported amblyopia risk factors in Peruvian children aged 3 to 15 years. Our analysis provides evidence of risk factors associated with amblyopia in a population where few related studies had been reported.

Previous studies reported an association between poverty and amblyopia [15, 16], arguing that in economically underdeveloped areas, the popularity of vision screening is relatively low, and the risk factors of amblyopia cannot be detected in time which could lead to delay in the early diagnosis and treatment of amblyopia. Additionally, risk factors such as low weight and poor prenatal care may be more frequent and cause a high prevalence of ocular morbidity in low-income populations. However, recent findings from previous meta-analyses demonstrate that prevalence is higher in high-income regions than in low-income regions [4]. However, our study did not find an association between economic status and amblyopia.

Some studies consider uncorrected refractive errors as the most common cause of amblyopia [5, 13, 14, 17]. In agreement, in our population, we found refractive errors pooled frequency higher than strabismus among amblyopic children. Both hyperopia (11.3% of cases), astigmatism (8.1%), or a combination of astigmatism + hyperopia (56.5% of cases) were found as major amblyogenic risk factors in the present study. While astigmatism is associated with amblyopia in different studies [12—14], hyperopia appears to be less relevant in other studies [12].

Strabismus remains a significant contributing factor to amblyopia in our study and was found in 25 of the 62 (40.3%) amblyopic children; this result is consistent with findings from previous studies [13, 14].

A significant association of amblyopia with prematurity (<37 weeks) has been previously reported [15, 18, 19], however, similar to other findings [12], we did not find significant associations between preterm birth with amblyopia in the present study. A possible reason was that the children were not premature or minus 32 weeks in our group, which has been shown to be significantly associated with increased ocular morbidity in other childhood studies [20].

Differences in age, ethnicity, disease definitions, and sociodemographic conditions make direct comparisons between some studies difficult. None of these studies were based in Latam, where the prevalence of amblyopia is high and where the public health and social conditions were substantially different, so it is worth noting that more research is needed in our regions about risk factors related to amblyopia.

Understanding the risk factors associated with the development of amblyopia is essential for several reasons: First, it can aid in the early detection and treatment of the condition, improving visual outcomes and quality of life for affected children. Second, it can inform public health policies and prevention strategies to reduce the incidence of amblyopia in children. Finally, it can provide insights into the underlying mechanisms of amblyopia, which may ultimately lead to the development of new treatments and interventions.

Vision impairment caused by amblyopia has severe consequences for the individual across the life course. However, many of these consequences can be mitigated by timely access to quality eye care and rehabilitation.

This study has limitations. First, its retrospective and single-center design may limit the generalizability of the findings to other pediatric populations. Second, the sample size was relatively small, which may have reduced the statistical power to detect associations with less frequent risk factors. Third, only variables available in medical records were analyzed, and potential confounders such as anisometropia magnitude, parental history of ocular disorders, or duration of visual deprivation could not be assessed. Finally, the use of univariable analyses may not fully account for interactions among ocular and non-ocular variables. Future multicenter, prospective studies with larger samples and standardized diagnostic criteria are warranted to validate and expand these findings.

Amblyopia was predominantly associated with refractive anomalies, most notably hyperopia and astigmatism, either isolated or in combination as well as with strabismus, whereas no significant associations were observed with perinatal or socioeconomic variables. These findings underscore the critical role of early detection and correction of refractive and ocular alignment disorders in mitigating amblyopia risk and emphasize the necessity for larger, prospective, multicenter investigations to further elucidate population-specific determinants of amblyopia within Latin American contexts.

Author Contributions:

Study concept and design: Rodríguez Plasencia C., Pomatanta Plasencia J., Contreras García C., Caballero-Alvarado J., Zavaleta-Corvera C.

Data collection: Rodríguez Plasencia C., Pomatanta Plasencia J., Contreras García C., Caballero-Alvarado J.

Statistical analysis: Rodríguez PlasenciaC., Pomatanta Plasencia J., Zavaleta-Corvera C.

Writing: C. Zavaleta-Corvera

Editing and final approval: Rodríguez Plasencia C., Pomatanta Plasencia J., Contreras García C., Caballero-Alvarado J., Zavaleta-Corvera C.

The authors declare no conflicts of interest.