Correlation Between Tear Film Stability and Myopia in Children

Introduction

Dry eye is a common disorder and the fifth most prevalent ocular condition among patients seeking eyecare.¹ According to the International Dry Eye WorkShop (DWES II) in 2017, dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film accompanied by ocular symptoms.² Dry eye is diagnosed based on clinical symptoms and signs, including the tear break-up time (TBUT), osmolarity, and ocular surface staining.³ Recent studies suggest that corneal epithelial thickness profiles may offer additional diagnostic value in differentiating dry eye from other conditions.⁴ The prevalence of dry eye increases with age and varies from 5% to 50%, depending on the diagnostic criteria used and population surveyed.⁵ In Taiwan, the annual crude incidence rate of dry eye increased from 1.46 per 1000 in 2001 to 4.26 per 1000 in 2015.⁶ However, only a limited number of studies have investigated the prevalence and characteristics of dry eye in children, due to children’s poorer ability to describe their symptoms, lack of attention and poorer cooperation of children with ophthalmic examination.⁷

Myopia causes blurred vision at a distance without correction. High axial myopia is also related to an increased risk of irreversible vision loss, including retinal detachment, choroidal neovascularization, cataracts, and glaucoma.⁸ The prevalence of myopia has markedly increased in children and young adults in East and Southeast Asia.⁹ In Taiwan, 86.1% of male military conscripts aged 18 to 24-years-old between 2010 and 2011 had myopia.¹⁰ The prevalence of high myopia (more than −6.0 D) among freshmen students at National Taiwan University increased from 23.5% in 1988 to 38.4% in 2005.¹¹ Among school children, the prevalence of myopia increased from 5.37% to 25.41% for 7-year-olds and from 30.66% to 76.67% for 12-year-olds between 1983 and 2017.¹² Hence, early detection of myopia and effective myopia-control strategies for children could benefit many patients.

There are some shared risk factors for dry eye and myopia, including age, near work activity, and long-term use of 3C electronic products.^5,7,13,14 Some treatments for myopia—including contact lenses and instillation of topical atropine—have also been proven to exacerbate dry eye.^15,16 Patients with pathologic myopia have lower TBUT scores and more severe dry eye symptoms compared to healthy adult individuals.¹⁷ However, only a few studies have evaluated the relationship between dry eye and myopia, especially in children. Previous reports demonstrated that the prevalence of dry eye was higher in school children with myopia compared to children without myopia (around 10%).^18,19 In addition, children with myopia have lower TBUT scores compared to emmetropic children.²⁰ However, the precise relationship between dry eye and the presence of myopia in school-aged children remains unclear. Thus to address this knowledge gap, the current study compared a cohort of Taiwanese school children with and without myopia to elucidate the correlation between dry eye and myopia.

Material and Methods

Subjects

This cross-sectional study included children aged 5–14-years-old who had received an ophthalmic examination at Keelung Chang Gung Memorial Hospital, Keelung, Taiwan between January 2021 and April 2022. All of the subjects were enrolled from the Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study, which contains the complete medical records and data on detailed physical examinations and serial blood analysis of the children since birth.²¹ The purpose of the PATCH study was explained to the parents of the participants and the parents provided written informed consent. This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital (Approval No.: 201901822A3) and followed the tenets of the Declaration of Helsinki.

The inclusion criteria were school-aged children who could undergo a complete eye examination and had no previous ocular disease. We excluded children who (1) had any eye(s) with combined ocular diseases (eg, cataracts, congenital retinal diseases, amblyopia, or strabismus) (2), who did not give consent (3) who had a previous history of surgery or any other ocular disease except for refractive errors, (4) or had any systemic disease that may affect visual acuity.

Questionnaire

Before clinical examination, each child completed the Ocular Surface Disease Index (OSDI) questionnaire and an activity questionnaire to assess the severity of dry eye and the child’s lifestyle, respectively. If the participants were too young to complete the questionnaire by themselves, trained ophthalmology staff interviewed the child and completed the questionnaire with the help of the child’s parents.

The OSDI questionnaire consists of twelve items designed to assess ocular symptoms, vision-related function, and environmental triggers. Based on the OSDI, the changes in the ocular surface were defined as normal (0–12), mild (13–22), moderate (23–32), or severe (33–100).⁶ An OSDI of more than 12 was defined as the presence of dry eye symptoms.

The activity questionnaire consisted of 12 questions on the total number of hours per week spent on near work and outdoor activities, as well as the duration of exposure to the sun. Items of near work include writing, near practice, computer use, mobile phone use, and television watching. Parental myopia was evaluated by asking “Does at least one parent of the child have high myopia (spherical power of −5 diopters²² or higher)?”; the answers were recorded as “yes” and “no”. If the child was unable to answer specific questions (eg, regarding parental myopia), responses were obtained directly from the accompanying parent or legal guardian.

Ocular Examination and Data Collection

All children underwent a detailed ophthalmic examination that included best-corrected visual acuity, measured refractive state after complete cycloplegia together with corneal power (Auto Ref/ Keratometer ARK-1a/ARK-1; Nidek, Gamagori, Aichi, Japan), slit-lamp biomicroscopy (BQ 900, Haag-Streit AG, Koeniz, Switzerland), external eye photography, and axial length (AL) measurement (IOLMaster 500, Carl Zeiss Meditec AG, Jena, Germany). Best-corrected visual acuity (BCVA) was measured using a Snellen chart and converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. Three trained ophthalmologists performed the ocular examinations and collected the data. The spherical equivalent (SE) was defined as the spherical power plus half of the negative cylinder power. In the current study, myopia was defined as an SE of −0.5 D or higher. All results were collected for the left eye.

Dry Eye Parameters

Schirmer’s I test measures tear volume by placing a paper strip on the lateral third of the lower eyelid after drying the inferior fornix without topical anesthesia.⁶ The length of the moistened portion of the strip was measured after 5 minutes.

The TBUT was measured by application of a single fluorescein strip to the inferior palpebral conjunctiva after instilling a drop of normal saline. The mean time for three replicates was recorded to assess tear film stability.⁶

Corneal fluorescein staining was graded using the National Eye Institute/Industry grading (NEI) scale.²³ Briefly, the NEI scale divides the cornea into five sections and assigns a value from 0 (absent) to 3 (severe) for each section, according to the amount, size, and confluence of punctate keratitis, with a maximum of 15 points.

The lid abnormality score was evaluated according to the grading scale proposed by Arita et al.²⁴ Four lid margin abnormalities (irregularity, telangiectasia, plugged meibomian gland orifices, and replacement of the mucocutaneous junction) were scored from 0 to 4 according to the number of these abnormalities in the examined eye.

In the current study, the diagnosis of dry eye disease was based on (1) the presence of dry eye symptoms (OSDI ≥ 12), (2) abnormal tear production as determined by Schirmer’s I test (≤ 5 mm), and (3) abnormal tear film stability as determined by the TBUT (≤ 5 seconds).^25,26

Statistical Analysis

The differences between the children with and without myopia were analyzed using Fisher’s exact test and the independent samples t-test for categorical and continuous data, respectively. Pearson’s correlation coefficient was used to assess the simple correlations between the OSDI and several variables, including age, time spent on near work or outdoor activities, spherical power, and AL. We also performed multiple linear regression analysis to evaluate the factors related to the OSDI via backward selection. Data were analyzed using SPSS (version 20.0; SPSS, Chicago, IL, USA). Statistical significance was defined as a two-tailed P-value of < 0.05.

Results

Medical records were collected for 69 eyes in 69 children. Four eyes from four children were excluded due to incomplete refractive data. A total of 31 non-myopic(average age, 9.03 ± 2.43 years) and 34 myopic (average age, 8.44 ± 2.18 years) children were included in the final analysis.

Table 1 summarizes the demographic data and refractive status of all children and the two groups. Compared to non-myopic children, myopic children had significantly higher negative spherical power (−1.65 ± 1.84 versus 0.77 ± 0.80 diopters, P < 0.001) and longer axial lengths (23.91 ± 1.04 versus 22.82 ± 0.92 mm, P < 0.001). There were no significant differences in the time spent on different activities or duration of sun exposure between the two groups.

Table 1 Characteristics of the Children with and without Myopia

Table 2 presents the dry eye parameters for children with and without myopia. In contrast to non-myopic children, myopic children had a significantly higher OSDI (4.79 ± 6.90 versus 1.68 ± 3.46, P = 0.024). Based on the criteria for the diagnosis of dry eye disease, a total of five children (7.7%) were diagnosed with dry eye (one non-myopic child and four children with myopia). The prevalence of dry eye disease was 11.7% in the myopic group and 3.2% in the non-myopic group, although the difference was not statistically significant (P = 0.358). There were no significant differences in the Schirmer test, TBUT, corneal fluorescein staining score, or lid abnormality score between groups.

Table 2 Dry Eye Parameters in the Children with and without Myopia

Table 3 shows the simple correlation analysis between the OSDI and myopic variables. The OSDI was significantly correlated associated with older age (Pearson’s correlation coefficient (r) = 0.25; P = 0.037) and more negative spherical power (r = −0.26; P = 0.036).

Table 3 Correlation Analysis of the OSDI and Myopic Variables

Multiple regression analyses of the OSDI and myopic variables (Tables 4 and 5) revealed the OSDI was significantly associated with more negative spherical power (B = −0.74, 95% CI = −1.48 to −0.01, P = 0.048) and the presence of myopia (B = 3.44, 95% CI = 0.72 to 6.16, P = 0.014) after adjusting for age.

Table 4 Linear Regression Analysis of the OSDI and Myopic Variable

Table 5 Linear Regression Analysis of the OSDI and Myopic Variables

Discussion

To the best of our knowledge, this is the first cross-sectional study to explore the correlation between dry eye and myopia in school-aged children (5–14 years). We found dry eye disease was more prevalent in myopic children than in non-myopic children (11.7% versus 3.2%, P = 0.358). Moreover, the group with myopia had a higher OSDI than the group without myopia. In addition, the OSDI was significantly correlated with older age and more negative spherical power. After adjusting for age, the OSDI remained significantly associated with negative spherical power and the presence of myopia.

Previous studies investigated the relationship between myopia and dry eye.^17,20 However, most studies only focused on adult populations. In this cohort, 11.7% of myopic children were diagnosed with dry eye disease, which is slightly lower than the rates reported in previous studies.^18,19 This difference may possibly be due to the use of different diagnostic methods. Wang et al found the prevalence of dry eye in Chinese myopic teenagers was 18.95%; however, they diagnosed dry eye using keratography.¹⁹ In a cross-sectional study conducted by Wang et al, the prevalence of dry eye in myopic children was 15.9%, and they observed dry eye was associated with picky eating and eye rubbing.¹⁸ Based on Table 2, although subjective symptoms OSDI differed significantly, objective measures such as TBUT and Schirmer’s test did not show significant differences. This suggests that early subjective symptoms of ocular discomfort may precede measurable tear dysfunction in myopic children.

The association between dry eye and increased higher-order aberrations, which may lead to further development of myopia, has also been investigated.²⁷ On the other hand, decreased tear film stability caused by dry eye increases the risk of higher-order aberrations.²⁸ In a study conducted in Japan, Yotsukura et al reported that more severe dry eye symptoms correlated with higher myopic refraction and longer axial length in elementary and junior high school students, respectively.²⁹ This finding is consistent with our results, as we found the OSDI was significantly associated with negative spherical power and the presence of myopia, and an intensive educational environment with both more near-work and fewer outdoor activities also contributes to this finding. Consistent with our findings, Harza et al reported that myopic individuals exhibited tear film instability and structural changes including reduced tear film breakup time, higher order aberrations, and alterations in choroidal thickness. These findings further support the hypothesis that anatomical and physiological changes in myopic eyes may contribute to dry eye symptoms, even in pediatric populations.³⁰

Orthokeratology and atropine are the main treatment strategies to reduce the progression of myopia in children. Some studies have pointed out that orthokeratology may alter tear stability by thinning the tear film lipid layer due to loss of the meibomian glands, conjunctival fold, and metaplasia and a reduction in goblet cell density.^31,32 However, the mechanisms that lead to lens-induced tear film instability remain controversial.^32–35 We were unable to conduct subgroup analysis based on treatments for myopia due to the limited numbers of patient. Hence, further thorough investigations of larger cohorts with subgroup analysis are needed to clarify the relationship between treatments for myopia and tear stability.

Studies have demonstrated a strong correlation between dry eye and the rate of smartphone use among pediatric populations.³⁶ In contrast, we found outdoor activity protected against pediatric dry eye. We observed no significant differences in the daily activities between myopic and non-myopic children, though this analysis may be limited by the small sample size. Differences in findings regarding screen time may be attributable to environmental, genetic, and methodological factors. Previous research also demonstrated that myopia is associated with being underweight rather than normal or high body mass index.³⁷ In general, parents and ophthalmologists should pay close attention and take caution regarding the duration of near activities for children.

The limitations of the current study include the small sample size, retrospective cross-sectional design, and subjective grading system for dry eye. However, all children underwent detailed ocular examinations as part of continuous follow-up at the same hospital (PATCH study) and a single ophthalmologist (P.W. Huang) graded the corneal fluorescein staining and lid abnormality score. These strengths help to compensate for data loss and the subjective grading system. Moreover, allergic conjunctivitis has a higher prevalence in children than adults and may be confused for dry eye symptoms,[25] which makes the diagnosis of dry eye more difficult. However, we diagnosed dry eye disease in children based on a combination of the OSDI, Schirmer’s I test, and the TBUT, which may improve diagnostic accuracy. Nevertheless, larger-scale studies are necessary to validate these findings.

In conclusion, children with myopia had a higher OSDI and higher prevalence of dry eye than children without myopia. After adjusting for age, the OSDI was associated with more negative spherical power and myopia. In general, further long-term, larger sample sizes and large-scale longitudinal studies of dry eye disease in myopic children are warranted to confirm these preliminary findings in the future.