Subjects
This study was conducted at the Beijing Tongren Hospital with the approval of the hospital’s Medical Ethics Committee (TREC-2017-KY021). All subjects were informed of the goals of the study, and their consent was obtained in accordance with the declaration of Helsinki. A total of 59 ADDE patients (36 women and 23 men; mean age 36.05 ± 12.56 years; range 18–72 years) were consecutively recruited from July 2018 to August 2019. According to the consensus report by the International Dry Eye Workshop (2007) [13], the inclusion criteria for the ADDE group were as follows: (1) age > 18 years; (2) Ocular Surface Disease Index (OSDI) score greater than 12; (3) tear film break-up time (TBUT) less than 10 seconds; (4) Schirmer I test at 5 minutes less than 10 mm. According to the severity-grading scheme of the 2007 Workshop [13], ADDE patients were divided into two groups (mild and severe). The severe ADDE group (28 patients) was including these patients with Schirmer I test ≤ 5 mm. The mild ADDE group (31 patients) consisted of patients with Schirmer I test between 5 and 10 mm. Thirty-one age- and gender-matched control subjects (21 women and 10 men; mean age 38.13 ± 13.79 years, range 18-67 years) were also recruited with Schirmer I test result exceeding 10 mm at 5 minutes, TBUT above 10 seconds and an OSDI score below 13. The exclusion criteria for both groups were as follows: (1) age < 18 years; (2) subjects unable to complete the questionnaire or understand the procedures; (3) best corrected visual acuity less than 20/20; (4) presence of ocular or systemic disease or the use of topical or systemic medications that may affect the ocular surface, and (5) previous history of eye surgery or contact lens wear.
Clinical Evaluation
Each subject underwent a quantification of ocular surface symptoms with the Ocular Surface Disease Index (OSDI) questionnaire (range 0-100) [14]. Optical quality and ocular surface examinations were then performed in the following order: double-pass optical quality analysis, lipid layer thickness measurement (LLT), TBUT and Schirmer I testing.
The lipid layer thickness was measured with the Lipiview II® device (Tear science, Morrisville, NC, USA). The interferometric color unit (ICU) value reflected the local LLT with 1 ICU equivalent to 1 nm of lipid layer thickness. TBUT was measured using sterile fluorescein strips impregnated with 0.6 mg fluorescein sodium (Alcon Laboratories, St. Louis, MO, USA). After applying 50 μL of normal saline solution to the paper strip, it was touched to the inferior fornix. The interval between a complete blink and the appearance of the first dry spot was noted. TBUT was measured 3 times and the average calculated. The Schirmer test was performed without anesthesia, after having the patient’s eyes closed for 5 minutes.
Objective scatter index measurement
The Optical Quality Analysis System (OQAS-II, Visiometrics, Tarrasa, Spain), was used to evaluate aberrations and intraocular scatter with the 2 following parameters: objective scatter index (OSI) and modular transfer function cut-off (MTF cut-off). The OSI is defined as the ratio between the integrated light in the peripheral ring and the central peak of the double-pass (DP) image. It represents the impact of aberration and scattering on the DP image. The MTF cut-off reflects the highest spatial frequencies that can be distinguished by patients’ eyes. The subjects were tested with their best correction and instructed to blink freely during the double-pass analysis. The “Tear Film Analysis” program of the commercially available OQAS device was used to record dynamic changes in OSI values. This program consisted of a 20-second examination with OSI measurement every 0.5 sec, providing a graph showing the change in OSI over time. The pupil size was set at 7 mm to cover the majority of the tear film. After measurement, the mean value and standard deviation of the 20-second OSI was available and recorded as "mean OSI" and "SD OSI," respectively.
After baseline examination, one drop of artificial tears (carboxymethylcellulose ophthalmic solution 0.5%, Refresh Plus, Allergan Pharmaceuticals, Ireland) was instilled in both eyes. Five and 30 minutes after application, the OQAS examinations were performed again in all subjects. The difference between the mean OSI at baseline and at 5 and 30 minutes (OSI5min, OSI30min) were analyzed, and the relationship between OSI and DED severity was evaluated.
Statistical analysis
Statistical analysis was performed with SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL, USA). For each subject, both eyes were tested, and the right eye was selected for analysis. All values were expressed as mean ± SD. The normality of the data was analyzed using the Shapiro-Wilk test. The normal data were compared before and after treatment with the paired t-test, and the non-normal data were used for the paired rank-sum test. A Bonferroni correction of multiple comparisons was included. The generalized estimation equation was used to compare the repeated measurement data at each time point and within each treatment group. The Spearman correlation test was used to evaluate the correlation betweenthe visual quality parameters and dry eye clinical tests. A P<0.05 was considered statistically significant.