It is not known how biological changes in the lacrimal (LGs) and meibomian (MGs) glands contribute to dry eye disease (DED) in a time-dependent manner. In this study, we investigated time-sequenced changes in the inflammation, oxidative stress, and senescence of stem cells in both glands of an aging-related DED mouse model. Eight-week (8W)-, one-year (1Y)-, and two-year (2Y)-old C57BL/6 male mice were used. MG areas of the upper and lower eyelids were analyzed by transillumination meibography imaging. The number of CD45⁺, 8-OHdG⁺, Ki-67⁺, and BrdU⁺ cells was compared in both glands. Increased corneal staining and decreased tear secretion were observed in aged mice. The MG dropout area increased with aging, and the age-adjusted MG area in lower lids was negatively correlated with the National Eye Institute (NEI) score. Increased CD4⁺ interferon (IFN)-γ⁺ cells in LGs were found in both aged mice. An increase in 8-OHdG⁺ cells in both glands was evident in 2Y-old mice. Reduced Ki-67⁺ cells, but no change in CD45⁺ cells, was observed in the MGs of 1Y-old mice. Increased BrdU⁺ cells were observed in the LGs of aged mice. This suggests that age-dependent DED in C57BL/6 mice is related to inflammation of the LGs, the development of MG atrophy, and oxidative stress in both glands.

Dry eye syndrome is one of the most common ocular diseases, and meibomian gland dysfunction (MGD) is the leading cause of evaporative dry eye syndrome. When the tear film lipid layer becomes thin due to obstructive or hyposecretory meibomian gland dysfunction, the excessive evaporation of the aqueous layer can occur, and this causes evaporative dry eye syndrome. Thus, measuring the lipid layer thickness (LLT) is essential for accurate diagnosis and proper treatment of evaporative dry eye syndrome. We used a white LED panel with a slit lamp microscope to obtain videos of the lipid layer interference patterns on the cornea. To quantitatively analyze the LLT from interference colors, we developed a novel algorithm that can automatically perform the following processes on an image frame: determining the radius of the iris, locating the center of the pupil, defining region of interest (ROI), tracking the ROI, compensating for the color of iris and illumination, and producing comprehensive analysis output. A group of dry eye syndrome patients with hyposecretory MGD, dry eye syndrome without MGD, hypersecretory MGD, and healthy volunteers were recruited. Their LLTs were analyzed and statistical information—mean and standard deviation, the relative frequency of LLT at each time point, and graphical LLT visualization—were produced. Using our algorithm, we processed the lipid layer interference pattern and automatically analyzed the LLT distribution of images from patients. The LLT of hyposecretory MGD was thinner (45.2 ± 11.6 nm) than that of dry eye syndrome without MGD (69.0 ± 9.4 nm) and healthy volunteers (68.3 ± 13.7 nm) while the LLT of hypersecretory MGD was thicker (93.5 ± 12.6 nm) than that of dry eye syndrome without MGD. Patients’ LLTs were statistically analyzed over time, visualized with 3D surface plots, and displayed using 3D scatter plots of image pixel data for comprehensive assessment. We developed an image-based algorithm for quantitative measurement as well as statistical analysis of the LLT despite fluctuation and eye movement. This pilot study demonstrates that the quantitative LLT analysis of patients is consistent with the functions of meibomian glands clinically evaluated by an ophthalmologist. This approach is a significant step forward in developing a fully automated instrument for evaluating dry eye syndrome and for providing proper guidance of treatment.

Background: To investigate the biomechanical properties of the cornea measured with the Ocular Response Analyzer (ORA) and their association with the anterior segment parameters representing the geometric dimensions including the corneal volume and anterior chamber volume.Methods: A retrospective review of 1020 patients who visited the BGN Eye Clinic was done. The mean radius of the corneal curvature, corneal astigmatism, corneal volume, anterior chamber depth, and anterior chamber volume were measured with an anterior segment tomographer. The central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The corneal diameter was measured with an Orbscan as White to White. Cornea hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg), and cornea-compensated IOP (IOPcc) were measured with an ORA. Multiple linear regression models were constructed with CH and CRF as the dependent variables and age, gender, and the anterior segment parameters as the covariates.Results: 958 eyes from 958 patients (mean age 26.7 years; male 43.4%) were included in this study after excluding some eyes according to the exclusion criteria. The mean CH and CRF were 10.1 and 9.9 mmHg, respectively. The mean IOPg and IOPcc were 14.8 and 15.8 mmHg. The multivariate analysis showed that CH was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.481, p = 0.023) and positively associated with CCT (regression coefficient =0.015, p < 0.001) and corneal volume (regression coefficient =0.059, p = 0.014). The association between CH and the corneal diameter, anterior chamber depth, and anterior chamber volume were not statistically significant. The evaluation of CRF showed that CRF was negatively associated with the mean radius of the cornea curvature (regression coefficient = - 0.540, p = 0.013), and positively associated with CCT (β = 0.026, p < 0.001). The association between CRF and the corneal diameter, corneal volume, anterior chamber depth, and anterior chamber volume were not statistically significant.Conclusion: The CH was shown to be positively associated with the corneal volume and the association between CH and the anterior chamber volume were not significant. The associations of CRF with the corneal volume or anterior chamber volume were not significant.

Background: The tear film breakup time (tBUT) is a clinical evaluation of evaporative dry eye disease assessed by instilling topical fluorescein into the eyes. In the present study, we introduce a new diagnostic test, blinking tolerance time (BTT), for self-evaluation of tear-film stability. We compared the results with the tBUT and validated the BTT test for self-assessment of tear film instability. Methods: This was a prospective controlled study involving 212 eyes of 106 participants 20–79 years of age. A total of 114 eyes of 57 dry eye patients and 98 eyes of 49 healthy subjects were included in the study. All patients and subjects were administered the following tests to diagnose dry eye disease: Ocular Surface Disease Index, BTT, tBUT, slit-lamp examination, corneal stain score, and Schirmer I test (without anesthesia). Patients and subjects were instructed not to blink for as long possible after reset blinking. The time interval between the reset blink and the next blink was measured. The mean of 3 tBUT values in both the right and left eyes was defined as tBUT_BE. Correlations between the BTT and tBUT_BE were also evaluated. To evaluate the diagnostic efficacy of the BTT and tBUT tests, receiver operating characteristic (ROC) curves were generated to obtain a cutoff score, and the sensitivities of the tests against the specificity at all possible thresholds were plotted. Results: Spearman’s correlation analysis revealed a significant weakly positive correlation between BTT and tBUT_BE (r = 0.447; p = 0.000). The intraclass correlation coefficient (ICC) of the tBUT was 0.679 (95% confidence interval [CI]: 0.575–0.765) and the ICC of the BTT was 0.904 (95% CI: 0.867–0.932). The area under the ROC curve did not significantly differ between the tBUT_BE (0.678) and BTT (0.628, p = 0.641). When the cutoff value of the BTT test was set to 8.1 s, the sensitivity was 63.3% and the specificity was 56.1%. Conclusion: The BTT test is a simple, inexpensive, and effective method for self-diagnosing dry eye that can also be used in the clinical setting.