This study was based on data from the 2010~2012 Korean National Health and Nutrition Examination Survey (KNHANES), a cross-sectional, population-based health examination and survey conducted by the Korea Centers for Disease Control and Prevention with Institutional Review Board approval7. The survey used multistage, stratified, probability cluster sampling to produce estimated health statistics representative of the noninstitutionalized civilian population of the Republic of Korea. The survey consisted of four components: a health-related interview, a health behavior survey, a health examination, and a nutrition survey. The interview included questions on demographics, socioeconomics, health, and nutrition. The health examination included vital signs, physiological measurements, and basic laboratory tests. We included subjects as AD patients who answered “yes” to the following question: “Have you ever been diagnosed as atopic dermatitis by doctor?.” This study adhered to the tenets of the Declaration of Helsinki for biomedical research involving human subjects. Approval for this study was obtained from the institutional review board/Ethics Committee of Soonchunhyang University Bucheon Hospital (approval number SCHBC 2017-12-014).

Participants underwent ophthalmic interviews, visual acuity measurements, intraocular pressure (IOP) measurements, autorefraction, slit-lamp examination, and fundus photography for their ophthalmic examinations. A past history of ophthalmic surgery and a family history of any ophthalmic disease were obtained from the interviews. The presence of dry eye disease was determined by following question: “Have you ever been diagnosed with dry eye disease by a doctor?” Available responses were “yes” or “no”. If a participant answered “yes,” he or she was classified as having clinical diagnosis of dry eye disease. A slit-lamp examination was performed to detect anterior segment abnormalities, evaluate the status of cataracts, and measure anterior chamber depth using the Van Herick method. The standard Lens Opacities Classification System (LOCS) III was used to categorize the type of cataract. Through a comparison with standard photographs, cataracts were categorized as cortical (LOCS III score ≥2), nuclear (LOCS III score ≥4 for nuclear opalescence or nuclear color), posterior subcapsular (PSC; LOCS III score ≥2), or mixed (more than one type of cataract per eye). The spherical equivalent was calculated as the sphere +1/2 cylinder. The IOP was measured once per eye from right to left with a Goldmann applanation tonometer (BQ-900; Haag-Streit, Bern, Switzerland) by a trained ophthalmologist. A digital non-mydriatic retina camera (TRC-NW6S; Topcon, Tokyo, Japan) and a Nikon D-80 digital camera (Nikon, Tokyo, Japan) were used to obtain digital fundus images under physiological mydriasis. Horizontal and vertical cup-to-disc ratios were measured from the fundus images, and features of diabetic retinopathy or age-related macular degeneration were checked.

A visual field test with frequency double technology was performed on participants with suspected glaucomatous features of the optic disc or an elevated IOP (≥22 mmHg). Suspected glaucomatous features of the optic disc included (1) a horizontal or vertical cup to disc ratio (VCDR) ≥0.5, (2) presence of optic disc hemorrhage, (3) presence of retinal nerve fiber layer defects, or (4) violation of the ISNT rule (i.e., normal eyes had a neuroretinal rim thickness configuration as follows: inferior>superior> nasal>temporal). Open-angle glaucoma was diagnosed using modified International Society of Geographical and Epidemiological Ophthalmology criteria for the Korean population. The specific diagnostic criteria were as follows: category 1 required both (1) a reliable visual field defect consistent with glaucoma (a fixation error and false-positive error ≤1 and the presence of at least two locations of reduced sensitivity) and (2) glaucomatous optic disc (neuroretinal rim loss with a VCDR or horizontal cup-to-disc ratio ≥0.6, presence of optic disc hemorrhage, presence of retinal nerve fiber layer defects, or asymmetry of the VCDR ≥0.2); category 2, if a visual field test was not available or was unreliable (a fixation error or false-positive error ≥2), required a VCDR ≥0.9, asymmetry of the VCDR ≥0.3, or presence of retinal nerve fiber layer defects and violation of the ISNT rule; category 3 required visual acuity ≤3/60 and IOP >21 mmHg. Subjects with a shallow anterior chamber (a peripheral anterior chamber depth less than or equal to one fourth of the central corneal thickness, indicating angle-closure glaucoma) were excluded.

Demographic and socioeconomic variables, including age, sex, urban or rural residence, income, and education level, were obtained from a health interview. Age was classified into 10-year intervals, income was stratified into quartiles, and education was categorized as elementary school or lower, middle school graduate, high school graduate and college graduate or higher. Regarding the region of residence, the 16 districts of the Republic of Korea were divided into two groups: (1) urban regions: Seoul, Gyeonggi, Busan, Daegu, Incheon, Gwangju, Daejeoun, and Ulsan; and (2) rural regions: Gangwon, Chungbuk, Chungnam, Jeonnam, Jeonbuk, Gyeongbuk, Gyeongnam, and Jeju. Occupation was classified into three groups: (1) white collar, comprising managers, professionals, clerical support workers, and service and sales workers; (2) blue collar, including agriculture, forestry, fishery, craft, and related trade workers; plant and machine operators and assemblers; and simple laborers; and (3) no occupation, including unemployed people, retired people, students, and homemakers. Body mass index (BMI) was calculated as follows: weight (kg)/height (m²). Smoking status was categorized as smoker, ex-smoker, or nonsmoker. Drinking habits were classified according to drinking frequency as following: none, ocassional (less than 2 times per week), and frequent (more than 2 times per week).

Systolic and diastolic blood pressure (BP) were measured three times using a standard mercury sphygmomanometer (Baumanometer; WA Baum, Copiague, NY, USA) in a seated position, and the mean values for systolic and diastolic BP were recorded. Subjects were defined as having hypertension if they had a history of taking antihypertensive medications or had a BP ≥140/90 mmHg. Participants who had been diagnosed with diabetes by physicians or had a fasting glucose level ≥126 mg/dl were defined as having diabetes mellitus, and hypercholesterolemia was defined as having a fasting total cholesterol level ≥240 mg/dl or taking oral lipid-lowering agents.

Statistical analyses were performed using SAS for Windows, version 9.3 (SAS Institute, Cary, NC, USA). The PROC SURVEY procedure with sample weights was used to account for a complex sampling design and to produce nationally representative prevalence estimates. We presented the demographic characteristics of the participants according to the presence of glaucoma as either means±standard errors (SEs) or proportions and compared them between groups using the Rao–Scott chi-square test. We performed 4-to-1 matching by adjusting age and sex. Multiple logistic regression analyses were conducted to determine the associations between AD and various ocular disorders. An adjusted model was developed that included occupation and region as potential confounders. Odds ratios (ORs) and 95% confidence intervals (CIs) were also calculated. In all analyses, a two-tailed p<0.05 was considered statistically significant.