Therefore, this study aims to assess the occurrence and analyze potential risk factors for DES in children under 18 years old before and during the COVID-19 pandemic, utilizing the database provided by the Korea Disease Control and Prevention Agency (KDCA) and the Korean National Health Insurance Service (NHIS).
Materials and Methods
Ethics statement
This study was approved by the Institutional Review Board of Jeonbuk National University Hospital (No. 2022- 02-054). The requirement for informed consent was waived because no personal information was included in the study. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.
Data source
This study utilized the database provided by the KDCA and the NHIS for policy and academic research purposes (No. KDCA-NHIS-2022-1-623). In Korea, it is mandatory for all citizens to enroll in the NHIS, which is a government- supported single-payer system. We used claims-based data for patients diagnosed with COVID-19 between October 8, 2020, and December 31, 2021, and those without a diagnosis of COVID-19. The database contains demographic information, medical records, and mortality data. To ensure privacy protection, these data have been de-identified.
Study cohort
This study aimed to investigate the occurrence of new DES in minors using claims data from the NHIS. DES cases were defined as having at least one diagnosis of “dry eye syndrome (H0411)” or keratoconjunctivitis sicca, not specified as “Sjögren syndrome (H1621)” based on the International Classification of Diseases, 10th Revision (ICD-10) codes.
We defined the term “COVID-19 season” to refer to the period from January 1, 2020, to December 31, 2020, which encompasses the time when COVID-19 infections were widespread, occurring more frequently, and when COVID-19-related policies and responses were intensified. In contrast, we designated the term “non-COVID-19 season” to represent the relative period from January 1, 2018, to December 31, 2018, which refers to a time when COVID-19 was not prevalent.
We randomly selected 1 million patients from those who had medical records in 2020 and had no record of DES or death in the same year, designating this cohort as the COVID-19 season cohort. Similarly, we randomly selected another 1 million patients from those with medical records in 2018 who did not die in the same year and had no DES record, after excluding patients overlapping with the COVID-19 season cohort. This group was designated as the non-COVID-19 season cohort. To focus specifically on minors, adults aged 19 years and older were excluded from both cohorts. The COVID-19 season cohort analyzed the DES occurrence in 2021, while the non-COVID-19 season cohort analyzed the DES occurrence in 2019 (
Fig. 1).
Variables
The variables used in this study were classified as follows. Age was categorized into two groups, 0-12 and 13-18 years;. Sex was classified as male or female. Economic status was divided into two categories, with the lower 50% designated as “low” and the remainder as “high.” Residential areas were categorized, with Seoul, Incheon, and Gyeonggi Province classified as metropolitan areas, while all other areas were classified as rural areas. Comorbidities were defined using ICD-10 codes, including hypertension (I10-I15, excluding I14), diabetes mellitus (DM; E10-E14), and hyperlipidemia (E78). This study aims to analyze the potential association between these variables and the occurrence of DES in minors, particularly in relation to the COVID-19 season and the non-COVID-19 season.
Statistical analysis
To evaluate the distribution of covariates between the COVID-19 season cohort and the non-COVID-19 season cohort, standardized mean differences (SMDs) were calculated. The SMD <0.1 was considered indicative of a balanced distribution of covariates. The primary outcome was the cumulative incidence of DES. The Kaplan-Meier method was used to estimate the survival curves of the COVID-19 season cohort and the non-COVID-19 season cohort during the follow-up period, the log-rank test was utilized to assess significant differences between the two cohorts. The incidence rate was calculated by dividing the number of newly diagnosed DES cases during the follow-up by the total observation time, indicated by person- years. The secondary outcome was the evaluation of the hazard ratio (HR) for DES between the COVID-19 season and the non-COVID-19 season. The HR, using the Cox proportional hazards model, along with the 95% confidence interval (CI), was used to evaluate the association between age, sex, comorbid disease, and the occurrence of DES. Crude HR considered the relationship between each individual variable and DES, while adjusted HR (aHR) accounted for all other individual variables. All tests were two-sided, and a p-value of <0.05 was considered statistically significant. SAS ver. 9.4 (SAS Institute Inc) and R ver. 3.2.3 (R Foundation for Statistical Computing) were used for the statistical analysis.
Discussion
This big data analysis using databases provided by the KDCA-NHIS, revealed a higher occurrence of DES in children under 18 years old during the COVID-19 season compared to the non-COVID-19 season. Moreover, older age, female sex, those living in metropolitan areas, and those with DM have been linked to DES. Other studies investigating the occurrence of DES in children in various countries during the COVID-19 pandemic have also reported an increased incidence of DES, corroborating our findings. For instance, a study by Tonkerdmongkol et al. [
10] identified increased self-reported symptoms of DES in Thai school children, while a cross-sectional study by Lin et al. [
11] reported a higher prevalence of DES among Chinese high school students using the Ocular Surface Disease Index and Perceived Stress Scale questionnaires.
However, it is important to note that most studies have assessed the prevalence of DES using Ocular Surface Disease Index questionnaires or other surveys. This variation in methodology makes direct comparisons challenging, particularly since our study utilized diagnostic codes to determine the prevalence. Additionally, previous research has predominantly focused on children aged 10 to 18 years, complicating comparisons with our broader age range that includes younger children. We aimed to capture the broader impact of COVID-19 on DES across all pediatric age groups rather than limiting our scope to a specific subset. Through the analysis of various risk factors influencing the occurrence of DES, it was found that individuals aged 13 to 18 years were at a higher risk of DES than those aged 0 to 12 years. Although our study focused on a sample cohort rather than the entire population, we believe it is meaningful to include the entire age range of children to provide a comprehensive analysis. However, further detailed analysis is needed to understand the differences between each age group.
Several studies have reported DES associated with increased screen time during the COVID-19 season. A study in Egypt suggested that increased screen time in children during the COVID-19 pandemic can contribute to symptoms of DES [
12]. Similarly, Alnahdi et al. [
13] showed that increased screen time has been associated with a higher incidence of DES in the pediatric population of the Western Region of Saudi Arabia during the COVID-19 pandemic. In the present study, we did not specifically measure screen time to elucidate the relationship between screen time and the prevalence of DES. However, considering the higher prevalence of DES among children aged 13 to 18 years compared to those aged 0 to 12 years, it is plausible that adolescents are more likely to engage in online educational activities, such as non-face-to-face classes. This increased screen time may consequently contribute to a higher incidence of DES [
14-
16]. Extended use of screens can induce DES by reducing the blink rate and causing increased evaporation from the ocular surface. These symptoms—such as dryness, irritation, pain, eye fatigue, and impaired vision—can adversely affect academic activities. During the COVID-19 pandemic, schools in Korea were closed and education was shifted to online platforms to maintain continuity. This transition to online learning has significantly increased the time children spend on digital devices, which may negatively impact the ocular surface and contribute to the development of DES. However, conclusive evidence regarding increased screen time leading to DES is lacking and there has been no known the number of people with DES actually decreased when restrictions were released [
17,
18]. Additional research is needed on the incidence of DES in relation to actual increases and decreases in screen time.
Girls exhibited a higher risk of DES compared to boys in our study, consistent with previous findings on the association between sex and DES incidence. This could be attributed to endocrine abnormalities contributing to DES, such as menopause and menstrual cycle variations [
19,
20]. However, there are few studies reporting the differences in prevalence between sex in the pediatric population [
21,
22]. For instance, Alnahdi et al. [
13] found no statistically significant difference between genders. Conversely, another study reported a higher prevalence in boys [
21]. In our study, girls continued to exhibit a higher risk of DES compared to boys, echoing previous research on hormonal influences and DES prevalence.
Individuals with a higher economic status and residing in metropolitan areas showed a slightly higher risk of DES compared to those in rural areas. Elhusseiny et al. [
12] found that educational screen time was significantly less in rural residents compared to urban dwellers. Another report also demonstrated that rural residence correlated with reduced rates of DES symptoms [
23]. These previous studies suggest that lower outdoor activities, increased screen time, and environmental factors such as climate and particulate matter are relevant risk factors for DES [
24,
25]. Although actual screen time and outdoor activity duration according to the two regions and economic status were not investigated, our study results also suggest that factors such as educational screen time, outdoor activity duration, climate, and other environmental factors, as demonstrated in previous research, may contribute to differences in DES incidence rates.
The presence of hypertension, DM, and hyperlipidemia showed a higher HR for DES compared to their absence. These findings are consistent with previous studies [
26-
30]. However, previous research has not specifically focused on children. Therefore, additional research is needed to investigate the relationship between underlying diseases such as hypertension, DM, and hyperlipidemia and the prevalence of DES in the pediatric population.
This study has some limitations. First, there is no objective scoring scale for DES, and diagnosing DES based solely on subjective symptoms may not accurately represent the true DES diagnosis [
31]. Additionally, using diagnosis codes for patient selection may not always reflect the actual clinical situation, as some patients included in the cohort may not have been accurately diagnosed during the specified period. Moreover, the use of DES codes when prescribing artificial tear drops may inflate the number of reported DES cases due to the financial incentives in the healthcare system. We could have examined the co-prescribed eye drops to exclude patients who received a diagnostic code for DES without actually having symptoms, simply to obtain artificial tears. However, this approach is also not entirely accurate, and it is difficult to definitively determine that these patients do not have DES. Therefore, we chose to analyze based solely on the diagnostic codes. To mitigate some of the potential errors, we excluded cases where DES was diagnosed in conjunction with keratoconjunctivitis codes, as these are more likely to represent instances where the DES code was used primarily for prescribing artificial tears. This exclusion reduces the risk of overestimating DES prevalence due to such practices. Nevertheless, this remains a common limitation in studies relying on big data and diagnostic codes. Finally, it is important to note that this study did not directly measure or analyze specific factors such as screen time, masking, and outdoor exposure. Our findings a re based on diagnostic codes, and while these factors are hypothesized to contribute to the increased prevalence of DES, further research is needed to investigate their impact directly.
Despite these limitations, our study has several strengths. While there is ample research on DES in adults, there is limited data available on the pediatric population. To the best of our knowledge, this study is the first large-scale cohort analysis of DES occurrence and prevalence, as well as potential risk factors, in individuals under 18 years during the COVID-19 season compared to the non-COVID-19 season. Furthermore, unlike previous studies, our analysis utilized diagnosis codes from the KDCA-NHIS, providing a unique perspective on DES-related eye diseases during the pandemic. Several contributing factors were identified, including frequent masking, increased use of smart devices, reduced outdoor exposure, endocrine factors, and social infection control measures. Sharing this information with parents, school staff, and educators to formulate preventive measures would be beneficial. It is worth considering initiatives like establishing guidelines or launching campaigns for online education, which promote the importance of incorporating breaks during online learning sessions and encouraging physical activity at home. Given the recent resurgence of COVID-19 infections, we believe that our findings are timely and crucial for understanding the impact of pandemics on children’s eye health, serving as a valuable resource for future research and public health planning, especially in preparing for and preventing potential future pandemics.
In conclusion, this study demonstrates a rise in the diagnosis of DES among children during the COVID-19 pandemic compared to previous years. Children aged 13 to 18 years, female sex, those living in metropolitan areas, and those with DM had a higher risk of DES. We suggest potential contributing factors such as frequent masking, increased use of smart devices, low outdoor exposure, mental stress, and depression under quarantine and social infection control measures. Further research is needed to directly analyze these factors associated with crisis akin to COVID-19.