Categorization of Meibomian Gland Dysfunction Using Lipid Layer Thickness and Meibomian Gland Dropout in Dry Eye Patients: A Retrospective Study.

PURPOSE: In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout. METHODS: Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups. RESULTS: Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group. CONCLUSIONS: This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.

Evaluation of lipid layer tear film changes after femtosecond small incision lenticule extraction.

Background: Dry eye disease is common after refractive procedures due to tear film instability. There are several causative factors for tear film instability, but the state of individual components of the tear film is not assessed much in published literature. This article quantifies the lipid layer thickness (LLT) of the tear film using surface interferometry before and after the small incision lenticule extraction (SMILE) refractive procedure. Objectives: This study aimed to evaluate the effects of femtosecond SMILE on the postoperative stability of the LLT of the tear film. Design: This was a prospective, interventional, non-case-control study. Methods: A total of 160 eyes of 80 patients were enrolled in the study. The follow-up period was 6 months after surgery. A noninvasive surface interferometer was used to measure the thickness of the lipid layer before surgery and was repeated at 3 and 6 months after surgery. The main outcome measure was the change in average LLT at 3 and 6 months after SMILE and its statistical significance. Results: There were 48 women and 32 men. Age ranged from 21 to 42 years (mean = 27 ± 6.4). Mean LLT at baseline was [oculus dextrus (OD) = 53.38 (±7.24) nm; oculus sinister (OS) = 52.21 (±6.95) nm], at 3 months [OD = 54.38 (±5.75) nm; OS = 53.26 (±5.70)], and at 6 months [OD = 53.31 (±5.66) nm; OS = 52.39 (±5.94)]. Mean LLT showed mild improvement at 3 months after surgery (OD = 53.38-54.38 mm, p = 0.0417; OS = 52.21-53.26 mm, p = 0.0398). There was no significant change in LLT from the baseline before surgery to levels 6 months after surgery (p = 0.8914 OD; p = 0.7368 OS). Conclusion: The SMILE refractive procedure did not alter the LLT that remained stable and adequate at 6 months postoperative follow-up.

Lipid layer thickness decrease due to meibomian gland dysfunction leads to tear film instability and reflex tear secretion.

PURPOSE: To determine the clinical effects of ocular surface and Meibomian gland parameters on tear film stability among individuals with Meibomian gland dysfunction (MGD), those with aqueous deficient dry eye (ADDE), individuals with both conditions and normal controls. METHODS: Patients were divided into four groups: normal controls, patients with ADDE, patients with MGD, and patients who fulfilled diagnostic criteria for ADDE and MGD (Mixed Group). Data for ocular symptom score, lid margin abnormality, ocular staining, tear break-up time, meiboscore, and lipid layer thickness (LLT) measured by a Lipiview interferometer, Schirmer test, and MGD severity score were collected. RESULTS: A total of 109 patients (109 eyes) were evaluated. In patients with MGD, LLT was significantly lower than the ADDE patients. However, the Schirmer test value was the highest in the MGD group. The LLT negatively correlated with meiboscore and MGD severity score in the MGD group. Significant correlation between Schirmer test value and meiboscore was definite in the MGD group. CONCLUSIONS: Tear fluid secretion is more increased and lipid layer thickness is more decreased in MGD patients than in ADDE patients. Decreased lipid layer thickness caused by MGD-related tear film instability may stimulate reflex tear secretion. The obstructive MGD is more prevalent than hypersecretary MGD.Key messagesThe tear film stability is affected by Mebomian gland dysfunction (MGD). The measurement of the tear film parameters including lipid layer thickness suggests that the obstructive MGD is more prevalent than hypersecretary MGD and the aqueous layer compensates the decreased lipid layer caused by MGD.

Orthokeratology Lens Wear for 2 Years in Children Did Not Alter Tear Film Lipid Thickness by Non-Invasive Interferometry.

PURPOSE: Previous studies suggest that overnight orthokeratology (OOK) may be detrimental to tear function. We aimed to investigate the effect of OOK on lipid layer thickness (LLT), blink pattern, and meibomian gland and elucidate the relationship of these variables. METHODS: Thirty-seven participants who wore OOK lenses every night for at least 2 years and twenty-four healthy non-contact lens wearers (controls) were enrolled in this retrospective study. LipiView interferometry, blink pattern analysis, the ocular surface status, and morphology and function of the meibomian gland were determined. RESULTS: The OOK group and healthy controls had similar LLT, blink patterns, ocular surface status, and the function of the meibomian gland. OOK participants demonstrated higher meiboscore in the lower eyelids (p < 0.05) but not in the upper eyelids. Within the OOK group, LLT was significantly impacted by the partial blink rate (p < 0.05) and the total score of the upper meibomian gland (p = 0.10). CONCLUSIONS: Wearing OOK for 2 or more years increased lower eyelid meibomian gland dropout but did not have a reduction of LLT.

Effects of meibomian gland dysfunction and aqueous deficiency on friction-related disease.

PURPOSE: To evaluate the effects of meibomian gland dysfunction (MGD) and aqueous deficiency (AD) on friction-related disease (FRD). METHODS: Cross-sectional comparative study. This study included 550 eyes (550 patients) with dry eye disease (DED). The DED subtype and dynamic tear-film parameters by automated assessments were investigated for the analysis of FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy). RESULTS: Patients with FRD had a higher proportion of moderate-to-severe MGD and AD (p < 0.001 and p < 0.001, respectively). The dropout rate of the meibomian gland was higher (30.5 ± 31.8 and 14.1 ± 25.0%, p < 0.001), tear meniscus height (TMH) was lower (227.8 ± 60.4 and 241.7 ± 55.6 µm, p = 0.008), and he first non-invasive keratographic tear break-up time (NIKBUT-1) was shorter (5.9 ± 3.5 and 7.3 ± 3.7 s, p < 0.001) in patients with FRD than in those without FRD. In the logistic regression analysis with clinical manifestation, both moderate-to-severe MGD and AD were associated with FRD (odds ratios [OR] 12.27, 95% confidence interval [CI] 7.72-19.50, and 2.31, 95% CI 1.43-3.71], p < 0.001 and p < 0.001, respectively). The dropout rate was positively associated with FRD (OR 1.017, 95% CI 1.010-1.023, p < 0.001). TMH and NIKBUT-1 were negatively associated with FRD (OR 0.995, 95% CI 0.991-0.999, and 0.90, 95% CI 0.85-0.95, p = 0.039 and p < 0.001, respectively). CONCLUSIONS: This study showed that FRD was highly associated with MGD and meibomian gland dropout rate, suggesting that FRD may be mainly affected by lipid components. AD and TMH also had a good but relatively lower association with FRD, compared to MGD and meibomian gland dropout rate.

Impact of virtual reality headset use on eye blinking and lipid layer thickness.

PURPOSE: Blinking plays an important role in protecting the eyes, and the use of computers has been associated with a reduction in the blink rate. The goal of this study was to evaluate the effect of a virtual reality headset on blinking and lipid layer thickness and to compare these data to those associated with a conventional desktop monitor. METHODS: Two experiments were performed to compare the effect of 20minutes of use of a virtual reality headset (FOVE) and 20minutes of use of a desktop monitor on the frequency and length of blinks (experiment 1, 15 participants) and on the thickness of the lipid layer as measured by Lipiview (experiment 2, 12 participants). RESULTS: In the first experiment, the blink rate [F(1.83)=4.3, P=0.04, ß=0.36] and duration [F(1.83)=13, P=0.001, ß=0.35] increased with time under both conditions, but no statistical difference was found between the two conditions (headset vs. desktop monitor) either for blink rate [rmANOVA F(1.11)=0.01, P=0.92; headset: 15.1 blinks, 95% CI: 12.6 to 17.6 blinks; desktop: 14.6 blinks, 95% CI: 13.6 to 15.7 blinks] or for blink duration [rmANOVA F(1.11)=4.534, P=0.06; headset: 205.75ms, 95% CI: 200.9 to 210.6ms; desktop: 202.82ms, 95% CI: 198.2 to 207.5ms]. However, strong individual variations were observed. Evaluation of simulator sickness and visual fatigue by questionnaire showed no significant differences between the two conditions (SSQ simulator sickness questionnaire: V=46, P=0.62; VFQ visual fatigue questionnaire: V=15.5, P=0.13). In the second experiment, the lipid layer thickness increased significantly after use of the VR headset [F(1.18)=11.03, P=0.004, headset: 76.2nm, desktop: 58.8nm]. CONCLUSION: In terms of recommendations, the effect of virtual reality headsets on blink duration and frequency during a moderate exposure (20minutes) is comparable to that of a conventional desktop monitor. However, the strong individual variations observed, the lack of reliable tests to evaluate this individual sensitivity, and the significant increase in lipid layer thickness in experiment 2 suggest the value of a more detailed investigation, in particular with consideration of a longer exposure time and other tear film parameters.

Characteristics of dry eye patients with thick tear film lipid layers evaluated by a LipiView II interferometer.

PURPOSE: To investigate the characteristics of eyes with dry eye disease (DED) whose lipid layer thickness (LLT) measured 100 nm on a LipiView II interferometer and compare the DED parameters of them to those with LLT below 100 nm. METHODS: A total of 201 eyes of 102 enrolled DED patients (mean age 56.4 ± 11.8 years) were classified into 3 groups according to their average LLT; < 60 nm as thin-LLT (n = 49), 60-99 nm as normal-LLT (n = 77), and 100 nm as thick-LLT (n = 75). LLT, meiboscore, Schirmer I test, tear film break-up time (TBUT), ocular surface staining (OSS), and ocular surface disease index (OSDI) were assessed. RESULTS: The OSS and TBUT were significantly worse in the thick-LLT group than in the normal-LLT group (p = 0.020, and p = 0.028, respectively). The OSDI was significantly higher in the thick-LLT group than in the thin-LLT group (p = 0.006). However, the meiboscore was not different among the three groups (p = 0.33). Age, OSS, and OSDI showed a positive correlation with LLT (r = 0.16, p = 0.023; r = 0.213, p = 0.003; and r = 0.338, p = 0.001, respectively). In sensitivity analyses, eyes with corneal erosions had a significantly higher average LLT (p = 0.015), higher OSDI (p = 0.009), shorter TBUT (p < 0.001), and shorter Schirmer I value (p = 0.024) than those with clear corneas. CONCLUSION: The average LLT of eyes with corneal erosions was thicker than those without erosions, suggesting that the LLT of 100 nm in the eyes with corneal erosions should not be regarded as a stable physiologic condition. Cautious interpretation of LLT along with other dry eye parameters is required.

Assessment of tear film lipid layer thickness in patients with Meibomian gland dysfunction at different ages.

BACKGROUND: To evaluate the correlations between lipid layer thickness (LLT) and morphology and function of the meibomian glands in patients who were diagnosed as meibomian gland dysfunction (MGD) in different age groups. METHODS: Patients who have diagnosed as obstructive MGD were included in this prospective, cross-sectional study. Patients were divided into three groups: young (ages 20-39 years), middle-aged (ages 40-59 years), and older (aged ≥60 years). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and were evaluated for LLT, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT) measurement, invasive TBUT (ITBUT), corneal fluoresceinstaining (CFS) score, eyelid margin abnormalities, Schirmer I test, and MG function and morphology, by using the Keratograph 5 and LipiView interferometer. RESULTS: Two hundred and nine patients (209 eyes) were included. The median LLT of all patient was 57 nm (IQR, 36.5 nm), and the LLT values were significantly different among the young group (median, 51 nm; IQR, 23.5 nm), middle-aged group (median, 59.5 nm; IQR 46.5 nm) and older group (median, 62 nm; IQR, 42.5 nm) (P = 0.033, Kruskal-Wallis test). In regression analyses controlling for confounder factors sex and MG loss, the LLT was positively correlated with age (ß = 5.539, P = 0.001). There was a negative correlation between LLT and MG dropout in the all (r = - 0.527, P < 0.001), young (r = - 0.536, P < 0.001), middle-aged (r = - 0.576, P < 0.001), and older (r = - 0.501, P < 0.001) groups. LLT was positively correlated with the MG expressibility in the all (r = 0.202, P = 0.003), middle-aged (r = 0.280, P = 0.044) and older (r = 0.452, p < 0.001) groups, but it was no statistical significance in the young group (r = 0.007, P = 0.949). CONCLUSIONS: The thickness of LLT was increased with age and significantly correlated with both MG secretion and morphology in middle-aged and older patients with obstructive MGD. LLT measurement is a useful screening tool for detecting obstructive MGD and age as an influential factor should be accounted for when interpreting the meaning of the LLT value. TRIAL REGISTRATION: NCT02481167 ; Registered 25 June, 2015.

Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma.

Purpose: To compare the lipid layer thickness (LLT) using the LipiView® ocular surface interferometer (TearScience® Inc, Morrisville, NC) between the eye treated with glaucoma medication and untreated normal eye in the unilateral glaucoma patients, and evaluate the effect of topical glaucoma medication on the LLT parameters in glaucoma eyes. Methods: The participants in this cross-sectional comparative study were unilateral glaucoma patients treated with topical glaucoma medications for more than 12 months. Three LLT parameters (average, minimum, and maximum) obtained by the LipiView® were compared between the glaucomatous eye and normal eye. The factors associated with LLT parameters in the eyes treated with glaucoma medication were investigated with multiple regression analysis. Results: Thirty patients with unilateral normal tension glaucoma were enrolled in the present study. Lipid layer average, minimum, and maximum were 64.83 ± 16.50, 51.63 ± 16.73, and 82.53 ± 20.62 in glaucomatous eyes, 77.26 ± 17.81, 62.83 ± 20.99, and 86.13 ± 15.42 in normal eyes. Lipid layer average and minimum were significantly thinner than those in normal eyes (P < 0.001, P < 0.001, respectively). Longer duration of glaucoma eye drops and a greater number of glaucoma medications were associated with the lower LLT average (ß = -0.456, P < 0.001, ß = -8.517, P = 0.003, respectively), and increasing glaucoma medications have a significant correlation with lower LLT minimum in glaucoma eyes (ß = -8.814, P = 0.026). Conclusion: The present study highlights that patients with long-term glaucoma medications need to be assessed for LLT parameters objectively evaluate their ocular surface health.

Comparison of meibomian gland dropout using two infrared imaging devices.

PURPOSE: To measure the degree of meibomian gland (MG) dropout in the lower eyelid determined by analysis of images obtained from the LipiView II (LVII) and the Keratograph 5M (K5M). METHODS: The inferior eyelid of each participant was imaged in a random order using both devices. All images were subjectively assessed by a single-masked investigator to determine the extent of MG loss using the Arita 4-point meiboscore grading scale. The images were also semi-objectively analyzed with ImageJ to calculate the percentage of MG dropout, by tracing around the non-glandular area and the total exposed area of the lower lid. RESULTS: Twenty participants (mean age 37 years, range 23-60, 60% female) completed the study. A significant difference in meiboscore (mean ±â€¯SD) was obtained between the LVII and the K5M (1.43 ±â€¯0.78 vs. 1.90 ±â€¯0.81, Z = 3.25, p = 0.001). The meiboscore 95% limit of agreement (LOA) ranged from -1.88 to +0.93. A significant difference was found with mean ImageJ percentage dropout between the LVII and the K5M (31.5% vs 43.4%, t = -4.8, p = 0.00003). The percentage dropout 95% LOA ranged from -42.79% to +19.06%. CONCLUSIONS: LVII images had significantly lower meiboscores and less percentage MG dropout. Varying amounts of dropout were observed between the devices due the amount of eyelid that was typically everted and because of differences in image quality. These results indicate that these devices should not be used interchangeably to evaluate MG dropout.

Correlation Analysis of Tear Film Lipid Layer Thickness and Ocular Surface Disease Index

PURPOSE: To analyze the relationship between ocular surface disease index and tear film lipid layer thickness (LLT) using a LipiView II® (LipiView® Ocular Surface Interferometer, TearScience®, Morrisville, NC, USA) interferometer. METHODS: Forty-nine patients diagnosed with dry eye syndrome were recruited for this prospective study. Patients completed ocular surface disease index questionnaires. We performed slit lamp examination, Schirmer test, corneal and conjunctival fluorescein staining, measured tear film break-up time, and graded meibomian gland dysfunction. Tear LLT, blinking time, and dynamic meibomian imaging were analyzed using a LipiView II® ocular interferometer. To control for missing data, we analyzed four sets of imputated data via the multiple imputation method and performed Pearson correlation analysis. Patients were assigned to one of two LLT categories (LLT < 60 or LLT ≥ 60) and Chi-square test was performed. RESULTS: Among ocular surface disease parameters, tear film break-up time (tBUT) had a statistically significant correlation with average and maximum LLT (average LLT; p = 0.008, 0.035, 0.006, 0.049, maximum LLT; p = 0.006, 0.042, 0.020, 0.049, Pearson correlation analysis with multiple imputation) but there was no significant correlation with minimum LLT (minimum LLT; p = 0.048, 0.090, 0.079, 0.039). Of the patients with a relatively thick average LLT or maximum LLT (LLT ≥ 60 nm), 80% and 88% had a tBUT < 10, respectively. Conversely, 39% and 47% of patients with relatively thin average LLT (LLT < 60 nm) had a tBUT < 10 (average LLT; p = 0.013, maximum LLT; p = 0.039). CONCLUSIONS: Average LLT and maximum LLT were significantly correlated with tBUT. Patients with a relatively thin average or maximum LLT tended to have a shorter tBUT. Based on these results, measuring tear film LLT using a LipiView II® interferometer may be useful in the diagnosis and follow-up of patients with evaporative dry eye.

Evaluation of Changes in Tear Film Lipid Layer Thickness Using Ocular Surface Interferometer after Artificial Tear Application

PURPOSE: The changes in tear film lipid layer thickness (LLT) after artificial tears application using LipiView®II interferometer were assessed. METHODS: We performed a prospective study of patients with dry eye disease. All subjects underwent measurement of tear film break-up time, Schirmer test, ocular surface staining, meibomian gland evaluation, and subjective score assessment using the Ocular Surface Disease Index. All subjects were randomly assigned to 1 of 3 groups using table of random numbers (group 1, sodium hyaluronate [HA] 0.1% eye drops without preservatives; group 2, HA 0.3% eye drops without preservatives and group 3, HA 0.1% with benzalkonium chloride 0.003%). LLT was measured before, immediately after and 1 hr, 3 hrs, and 6 hrs after artificial tears application. Additionally, the patients were divided into 2 subgroups depending on the presence of meibomian gland dysfunction (MGD) and further evaluated. RESULTS: Significant change in LLT was observed at 3 hrs after artificial tears instillation. LLT in groups 1 and 2 showed significant changes over time (p < 0.01 and p < 0.01, respectively). However, LLT in group 3 showed no change. LLT was unchanged in patients without MGD. Conversely, in MGD patients, a significant difference in LLT between groups 1 and 2 was observed immediately after and 1 hr and 3 hrs after instillation of artificial tears (p = 0.04, p < 0.01 and p = 0.02, respectively) but not at 6 hrs. However, no significant difference in LLT between groups 1 and 3 was observed in MGD patients. CONCLUSIONS: LLT after instillation of artificial tears measured using LipiView®II interferometer was affected by artificial tear concentration and presence of preservatives. Additionally, the presence of MGD can impact the pattern of LLT changes induced by artificial tear instillation. Therefore, LLT measurements using LipiView®II interferometer require at least a 6-hrs interval after use of eye drops, especially for patients with MGD or using artificial tears with preservatives.

The Effects of Warm Compression on Eyelid Temperature and Lipid Layer Thickness of Tear Film

PURPOSE: Warm compression using a commercial heat pad was used to evaluate the effects of temperature on the eyelids and tear film lipid layer thickness. METHODS: Targeting 13 patients (26 eyes) with non-specific eye disease such as dry eye syndrome or Meibomian gland dysfunction, we measured the average thickness of the tear film lipid layer in both eyes with the LipiView 2® System (Tearscience®, Morrisville, NY, USA). We performed warm compression on the right eye only in order to evaluate the effectiveness of massage and measured the temperature of the right eye lid immediately, 3 minutes, and 5 minutes after compression in order to compare with the untreated left eye. After warm compression for 5 minutes, we measured tear film lipid layer thickness of both eyes and analyzed the effectiveness of warm compression. RESULTS: The average tear film lipid layer thickness was 55.1 ± 21.0 nm in the right eyes and 53.9 ± 13.9 nm in the left eyes (p = 0.474). Before performing the warm compression, the temperature of the right eye lid was 53.9 ± 13.9 nm, and that of the left was 35.9 ± 0.2℃. The eye lid temperature of the right eye immediately, 3 minutes, and 5 minutes after warm compression was 40.3 ± 1.3℃, 40.3 ± 1.3℃, and 40.3 ± 1.9℃, respectively, and these temperatures were relatively constant during the massage. Tear film lipid layer thickness after warm compression in the right eye was 83.5 ± 18.8 nm, which was increased compared to the original temperature (p = 0.001) and showed significant difference compared with the 65.5 ± 27.1 nm in the left eye (p = 0.005). CONCLUSIONS: Warm compression increased the tear film lipid layer thickness and showed a relatively constant increased temperature of 40.3℃ over 5 minutes. This technique will be helpful for maintaining tear film lipid layer thickness in patients with Meibomian gland dysfunction.

The Effects of Warm Compression on Eyelid Temperature and Lipid Layer Thickness of Tear Film

PURPOSE: Warm compression using a commercial heat pad was used to evaluate the effects of temperature on the eyelids and tear film lipid layer thickness. METHODS: Targeting 13 patients (26 eyes) with non-specific eye disease such as dry eye syndrome or Meibomian gland dysfunction, we measured the average thickness of the tear film lipid layer in both eyes with the LipiView 2® System (Tearscience®, Morrisville, NY, USA). We performed warm compression on the right eye only in order to evaluate the effectiveness of massage and measured the temperature of the right eye lid immediately, 3 minutes, and 5 minutes after compression in order to compare with the untreated left eye. After warm compression for 5 minutes, we measured tear film lipid layer thickness of both eyes and analyzed the effectiveness of warm compression. RESULTS: The average tear film lipid layer thickness was 55.1 ± 21.0 nm in the right eyes and 53.9 ± 13.9 nm in the left eyes (p = 0.474). Before performing the warm compression, the temperature of the right eye lid was 53.9 ± 13.9 nm, and that of the left was 35.9 ± 0.2℃. The eye lid temperature of the right eye immediately, 3 minutes, and 5 minutes after warm compression was 40.3 ± 1.3℃, 40.3 ± 1.3℃, and 40.3 ± 1.9℃, respectively, and these temperatures were relatively constant during the massage. Tear film lipid layer thickness after warm compression in the right eye was 83.5 ± 18.8 nm, which was increased compared to the original temperature (p = 0.001) and showed significant difference compared with the 65.5 ± 27.1 nm in the left eye (p = 0.005). CONCLUSIONS: Warm compression increased the tear film lipid layer thickness and showed a relatively constant increased temperature of 40.3℃ over 5 minutes. This technique will be helpful for maintaining tear film lipid layer thickness in patients with Meibomian gland dysfunction.