Abstract

Background: Anisometropia is a common refractive error. It has been associated with an increased risk of developing amblyopia, a condition that can lead to permanent vision loss if left untreated. This study aimed to systematically review and pool the available evidence on the relationship between anisometropia and amblyopia.

Methods: A systematic review and meta-analysis was conducted following the PRISMA guidelines. Three main databases were searched for observational studies that addressed the association between anisometropia and the risk of developing amblyopia. The quality of the included studies was assessed using the Newcastle–Ottawa scale.

Results: A total of 14 studies were included in the meta-analysis, with a combined sample size of 6,895 participants. Patients with any refractive error had a higher risk of developing amblyopia compared to those without refractive errors (P<0.05). However, the risk of developing amblyopia in patients with refractive errors of less than 1 diopter was relatively small (OR: 1.66, 95% CI: 1.2, 2.12).

Conclusion: This systematic review and meta-analysis provide evidence of a significant association between anisometropia and the risk of developing amblyopia. This highlights the importance of early detection and treatment of anisometropia as a potential strategy for preventing amblyopia.

Introduction

Amblyopia, or lazy eye, refers to the reduction of vision in one or both eyes without any ocular pathology1. This condition involves a decrease in best-corrected visual acuity in one or both eyes that is not related to any structural eye problems or visual pathway abnormalities2. The visual impairment caused by this disease can affect the visual cortex of the brain and disrupt cortical connections in various brain regions such as the frontal and parietal cortices during the critical period of brain development. This can lead to impairments in decision-making, response, and quality of life3. According to a meta-analysis study conducted in China in 2019, the prevalence of amblyopia was 1.44% globally: 1.09% in Asia, 2.44% in North America, and 2.90% in Europe. The highest prevalence was 3.29% in individuals over 20 years of age, with no gender differences. Based on that study, an estimated 99.2 million people worldwide are affected by amblyopia, which will increase to 175.2 million by 2030 and 221.9 million by 20404.

A systematic review study conducted in 2018 showed that the prevalence of this disease in Iran was 3.69%5. Another study conducted in Iran in 2018 indicated that the prevalence of amblyopia between 1990 and 2018 had decreased in the provinces of Hormozgan, Tehran, and Qom, but it increased in 13 other provinces6.

Anisometropia refers to the difference in refractive error between the two eyes, with a difference of equal to or greater than 1 diopter. The prevalence of anisometropia is less than 18% before the age of 40, and most studies show a prevalence of less than 10%. The prevalence of anisometropia appears to be age-dependent and higher in adults than in children. Mild anisometropia can be tolerated with special glasses, but degrees greater than 4 diopters are susceptible to progressing toward amblyopia7. According to a meta-analysis study conducted in 2018, the global prevalence of amblyopia was 1.75%8.

Recognizing the risk factors of amblyopia and timely prevention and treatment can prevent visual impairment and improve quality of life. Several studies have been conducted on the relationship between anisometropia and the risk of developing amblyopia. Some have shown a significant relationship between the two, whereas others have found no significant association. Since no comprehensive meta-analysis study has been conducted to determine the relationship between these two diseases, this study aimed to investigate the relationship between anisometropia and amblyopia through a systematic review and meta-analysis of similar studies.

Methods

This article presents a systematic review and meta-analysis conducted to investigate the relationship between anisometropia and amblyopia. The systematic review methodology was developed using the checklist of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)9.

The study population included all patients with both amblyopia and anisometropia, without restrictions on age, gender, or race. Relevant studies on the relationship between anisometropia and the important risk factor of amblyopia were extracted from three main databases, Scopus, ISI Web of Science, and PubMed, from their inception until February 2022. They were entered into the meta-analysis by related keywords including “anisometropia,” “amblyopia,” and “reflective error”. All observational studies (cohort, case-control, and cross-sectional) that addressed the relationship between amblyopia and anisometropia were included in this meta-analysis, regardless of language, time frame, or publication status. To identify additional potential studies of interest, the reference lists of the selected articles were evaluated. The inclusion criteria were all studies that mentioned the outcome of amblyopia and exposure to anisometropia. The exclusion criteria were qualitative studies, editorials, case reports, case series, and review studies.

The electronic data collection form was designed to extract the necessary data, including the first author’s name, year of publication, country, study type, patient occupational group, mean age of patients, study type, sample size in the intervention and control groups, diagnostic criteria for amblyopia, and odds ratio (OR) in both crude and adjusted forms. The data extraction was completed by two independent reviewers (SK and TM).

The methodological quality of the studies was assessed based on the Newcastle–Ottawa and Ottawa Statement guidelines. These guidelines include criteria for selecting study participants, comparability, and exposure and outcome considerations, with a maximum of nine stars assigned to each study. Studies with seven or more stars were considered high-quality studies, and studies with six or fewer stars were classified as low-quality studies. The possibility of bias in the study results was separately assessed by two researchers, and any disagreement was resolved through discussion.

The effect of anisometropia on amblyopia was expressed in terms of OR with a 95% confidence interval (CI). The I2 statistic was calculated to evaluate the heterogeneity among the studies. For all analyses, a random effect model was reported. Stata 14 software was used to analyze the data.

× Figure 1 . Flowchart depicting the process of identifying, screening, and including studies for the systematic review and meta-analysis . Figure 1 . Flowchart depicting the process of identifying, screening, and including studies for the systematic review and meta-analysis .

Table 1.

Characteristics of studies included in the systematic review and meta-analysis

First Author Year Study-design Country Sample size Characteristics Magnitude of Anisometropia Adjusted OR (95%CI) Leon et al . 10 2008 Retrospective observational study USA 974 Mean age: 3.7 year (Range: 0-6) 2-4D vs. 1-2D >4D vs. 2-4D - 2.13 (1.63, 2.78] 2.34 (1.67, 3.28] Pai, Amy Shih-I et al . 11 2011 Population-based, cross-sectional study Australia 1422 30 to 72 months ≥ 1D age, gender, and ethnicity 27.82 (11.17-69.31) Huynh et al . 12 2015 population based study Australia 1724 Mean age: 6.7±0.4 year Boys: 50.7% - worse eye refraction, multiple birth and strabismus 29.3 (8.7 to 99) Borchert et al . 13 2009 Population-based, cross-sectional study USA 6024 Age: 6 to 72 months Race: Hispanic and African American children Spherical and cylindrical anisometropia (1.0 D) age, gender, and ethnicity Family amblyopia 3.5 (1.22–10.03 ) Ying, Gui-shuang et al . 14 2013 Multicenter, cross-sectional study USA 3728 3-5 year old ages SE: Any 0.25 D >0.25-0.5D >0.5, 0.75D >0.75-1.75D >1.75-12.3D - 3.34 (2.12–5.26) 0.78 (0.34-1.82) 1.52 (0.81–2.88) 4.89 (2.44-9.81) 11.5 (6.37-20.8)