Quantitative Assessment of Lid Margin Vascularity Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity. Methods: This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants. Results: Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = -0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001). Conclusions: LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future. Translational Relevance: We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.

Morphological and functional assessment of the tear film and meibomian glands in keratoconus.

PURPOSE: To evaluate morphological and functional state of the meibomian glands (MG) in keratoconus patients. METHODS: One hundred eyes of 100 keratoconus patients and 100 eyes of 100 age-matched control subjects were included into this study. Ocular Surface Disease Index (OSDI) scores, non-invasive break up time (NIBUT), findings of meibography, staining with fluorescein of the ocular surface, tear film break-up time (TBUT), and Schirmer I test were documented in all patients' eyes and control eyes and were compared between the groups . RESULTS: The mean TBUT and NIBUT were significantly lower, corneal staining and OSDI scores were statistically greater in the keratoconus group (p < 0.05). The mean meiboscore, partial gland, gland dropout and gland thickening scores for upper/lower eyelids were significantly greater in keratoconus patients than controls (p < 0.05). The NIBUT measurements significantly correlated with MG loss in upper/lower eyelids (p < 0.05). The severity of keratoconus seemed to correlate with meiboscore, partial gland, gland thickening scores in upper/lower eyelids. CONCLUSION: Our data suggests that corneal ectasia in keratoconus is related with alterations in ocular surface, tear film function and MG morphology. Early screening and treatment of MG dysfunction may improve ocular surface quality and allow better disease management in keratoconus patients.

Intraobserver Repeatability Assessment of the S390L Firefly WDR Slitlamp in Patients With Dry Eye Disease: Objective, Automated, and Noninvasive Measures.

OBJECTIVES: To assess the intraobserver repeatability of automated, objective, and noninvasive measures obtained with the S390L Firefly WDR slitlamp. METHODS: This cross-sectional study included 50 eyes of patients with dry eye disease with a mean age of 55.06±12.96 years. Three consecutively repeated measures of the following variables were obtained: first noninvasive break-up time (F-NIBUT), average noninvasive break-up time (A-NIBUT), tear meniscus height, tear meniscus area (TMA), nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival hyperemia (NCOH), temporal conjunctival hyperemia (TCOH), upper loss area meibomian gland (U-LAMG), lower loss area meibomian gland (L-LAMG), upper meibomian gland dysfunction grade (U-MGD grade), and lower meibomian gland dysfunction grade (L-MGD grade). Intraobserver repeatability was estimated with coefficient of variation (CoV), intrasubject standard deviation (SD) (S w ), and Bland-Altman plots. RESULTS: All variables showed no statistically significant differences in the repeated-measures analysis except for L-MGD grade ( P =0.045). F-NIBUT and A-NIBUT obtained the highest CoV with an average value of 0.48±0.41 [0.02-1.00] and 0.34±0.25 [0.02-1.00], respectively. The remaining variables showed CoVs between 0.04±0.11 [0.00-0.43] and 0.18±0.16 [0.00-0.75]. A-NIBUT, TMA, NCOH, and L-LAMG obtained an S w of 2.78s, 0.21 mm 2 , <0.001, and 4.11%, respectively. Bland-Altman plots showed a high level of agreement between pairs of repeated measures. CONCLUSION: The S390L Firefly WDR slitlamp has moderate intraobserver repeatability for F-NIBUT and A-NIBUT, which suggests that F-NIBUT and A-NIBUT are tests with high variability. The remaining variables show satisfactory intraobserver repeatability.

Role of instrumental factors in Meibomian gland contrast assessment.

PURPOSE: Meibomian gland contrast has been suggested as a potential biomarker in Meibomian gland dysfunction. This study analysed the instrumental factors related to contrast. The objectives were to determine whether the mathematical equations used to compute gland contrast (e.g., Michelson or Yeh and Lin), impact the ability to identify abnormal individuals, to ascertain whether contrast between the gland and the background could be an effective biomarker and to assess whether using contrast-enhancement on the gland image improves its diagnostic efficacy. METHODS: A total of 240 meibography images from 40 participants (20 controls and 20 having Meibomian gland dysfunction or blepharitis), were included. The Oculus Keratograph 5M was used to capture images from the upper and lower eyelids of each eye. The contrast of unprocessed images and those pre-processed with contrast-enhancement algorithms were analysed. Contrast was measured on the eight central glands. Two equations for contrast computation were used, and the contrast both between glands and within a gland were calculated. RESULTS: Significant differences were found between the groups for inter-gland area in the upper (p = 0.01) and lower eyelids (p = 0.001) for contrast measured with the Michelson formula. Similar effects were observed when using the Yeh and Lin method in the upper (p = 0.01) and lower eyelids (p = 0.04). These results were obtained for images enhanced with the Keratograph 5M algorithm. CONCLUSIONS: Meibomian gland contrast is a useful biomarker of disease related to the Meibomian glands. Contrast measurement should be determined using contrast-enhanced images in the inter-gland area. However, the method used to compute contrast did not influence the results.

Functional and morphological evaluation of the meibomian glands and ocular surface assessment at high altitude.

Purpose: To compare the function and morphology of the meibomian glands and the ocular surface of individuals from highland and lowland. Methods: This was a randomized controlled trial. The study was performed with 104 individuals (51 individuals from the highland and 53 individuals from the lowland). Detailed eye examinations comprising tear meniscus height, lipid layer grading, non-invasive Keratograph tear breakup time (NIKBUT), and scoring of the meibomian glands from the upper and lower eyelids of the individuals were performed by Keratograph 5M (OCULUS, Wetzlar, Germany). Symptoms related to dry eye disease were assessed using the Ocular Surface Disease Index (OSDI). Results: In the highland group, tear meniscus height was lower (P = 0.024), lipid layer grade, as well as all the meiboscores were higher (P < 0.05) than that in the lowland group. The OSDI (P = 0.018) and the percentage of dry eye disease were also higher as compared to that of the lowland group (P = 0.032). The first NIKBUT and average NIKBUT did not differ significantly between groups. The frequency of plugged meibomian gland orifices was greater in the lowland group compared to the highland group (P = 0.036). Conclusion: It was observed that dry eye disease was more common in the highland group. The morphological changes of meibomian gland dropout were significant in highlanders as demonstrated objectively with Keratograph 5M. Our study may raise a concern for environmental influences on ocular surface changes.

Assessment of Laser Parameters to Improve Lid Tension-A Proof of Concept towards Lasercanthoplasty.

BACKGROUND: Preliminary clinical work indicates that increasing eyelid tension improves the function of the meibomian glands. The aim of this study was to optimize laser parameters for a minimally invasive laser treatment to increase eyelid tension by coagulation of the lateral tarsal plate and canthus. METHODS: Experiments were performed on a total of 24 porcine lower lids post mortem, with six lids in each group. Three groups were irradiated with an infrared B radiation laser. Laser-induced lower eyelid shortening was measured and the increase in eyelid tension was assessed with a force sensor. A histology was performed to evaluate coagulation size and laser-induced tissue damage. RESULTS: In all three groups, a significant shortening of the eyelids after irradiation was noticed (p < 0.0001). The strongest effect was seen with 1940 nm/1 W/5 s, showing -15.1 ± 3.7% and -2.5 ± 0.6 mm lid shortening. The largest significant increase in eyelid tension was seen after placing the third coagulation. CONCLUSION: Laser coagulation leads to lower eyelid shortening and an increase in lower eyelid tension. The strongest effect with the least tissue damage was shown for laser parameters of 1470 nm/2.5 W/2 s. In vivo studies of this effect have to confirm the efficacy of this concept prior to clinical application.

Development of Artefact-Free Imaging System for Accurate Meibomian Gland Reflectivity Assessment.

Purpose: To develop and evaluate a custom imaging system to provide high-resolution, wide depth-of-field, reflection-free, multispectral infrared (IR) imaging of the Meibomian glands. Methods: Lower eyelids of 15 volunteers were everted to obtain multispectral images of the Meibomian glands with custom imaging setup. Photographs were captured at 10 different ISO settings (from underexposure to overexposure) and using nine IR imaging filters (ranging from 600 nm to 1000 nm in 50-nm steps). Meibomian gland contrast (simple and Michelson) was calculated for the images to choose an optimal wavelength for Meibomian gland imaging and to determine differences in contrast across individuals. Results: The overall linear regression model showed a significant effect of wavelength on Meibomian gland contrast (Simple contrast: F = 7.24, P < 0.0001; Michelson contrast: F = 7.19, P < 0.0001). There was a significant negative correlation between Meibomian gland contrast and Meibomian gland depth for 750-nm IR filter (ρs= -0.579; P = 0.026). Conclusions: Meibomian gland contrast varies across individuals and depends on Meibomian gland depth. IR filter of 750 nm is the optimal choice for Meibomian gland imaging because it provides images of greatest contrast. Translational Relevance: This study adds to our understanding of Meibomian gland imaging. It has successfully demonstrated that Meibomian glands that are deeper in the tarsal plate require longer wavelengths for imaging.

Ocular surface assessment and morphological alterations in meibomian glands with non-contact meibography in electronic cigarette smokers.

PURPOSE: The study aimed to evaluate the ocular surface and meibomian gland morphology in electronic cigarette (e-cigarette) smokers. METHODS: The upper and lower eyelids of 25 male e-cigarette smokers and 25 healthy male non-smoker patients were evaluated using Sirius meibography. Meibomian glands loss was automatically calculated using Phoenix meibography imaging software module, with the result obtained as percentage loss. Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time test, and Schirmer II test were administered and performed in all cases. RESULTS: The mean e-cigarette smoking duration was 4.9 ± 0.9 (range, 3.4-7) years. While the mean Schirmer II test value was 9.16 ± 2.09 mm in e-cigarette group, it was 11.20 ± 2.14 mm in control group (p=0.003). Mean tear breakup time was 6.96 ± 2.31 seconds in e-cigarette group and 9.84 ± 2.13 seconds in control group (p=0.002). The mean OSDI value was 28.60 ± 6.54 and 15.16 ± 7.23 in e-cigarette and control groups, respectively (p<0.001). In Sirius meibography, the average loss for the upper eyelid was 23.08% ± 6.55% in e-cigarette group and 17.60% ± 4.94% in control group (p=0.002), and the average loss for the lower eyelid was 27.84% ± 5.98% and 18.44% ± 5.91%, respectively (p<0.001). Additionally, a significant positive correlation was identified between the loss rates for both upper and lower eyelid meibography with e-cigarette smoking duration (r=0.348, p<0.013 and r=0.550, p<0.001, respectively). CONCLUSION: Long-term e-cigarette smoking causes damage to the meibomian glands; therefore, meibomian gland damage should be considered in ocular surface disorders due to e-ci-garette smoking.

Assessment of meibomian gland drop-out and visibility through a new quantitative method in scleral lens wearers: A one-year follow-up study.

OBJECTIVES: To validate a previously developed algorithm based on the visibility of meibomian gland images obtained with Cobra fundus camera and to assess the changes in meibomian glands in scleral lens wearers over one year of lens wear. METHODS: Infrared meibography was obtained from the upper eyelid using the Cobra fundus camera in forty-three volunteers (34.2 ± 10.1 years). Meibographies were classified into 3 groups: Group 1 = good subjective gland visibility and gland drop-out < 1/3 of the total area; Group 2 = low visibility and gland drop-out < 1/3; and Group 3 = low visibility and gland drop-out > 1/3. Meibomian gland visibility metrics were then calculated using the developed algorithm from the pixel intensity values of meibographies. Repeatability of new metrics and their correlations with gland drop-out were assessed. Meibographies and ocular symptoms were also assessed after 1 year of scleral lens wear in 29 subjects. RESULTS: Gland drop-out percentage was not statistically different between groups 1 and 2 (p = 0.464). Nevertheless, group 1 showed higher grey pixel intensity values than the other groups. Statistically significant correlations were found between gland visibility metrics and gland drop-out percentage. Repeatability was acceptable for all metrics, coefficient of variation achieving values between 0.52 and 3.18. While ocular symptoms decreased with scleral lens wear (p < 0.001), no statistically significant differences were found in gland drop-out percentage (p = 0.157) and gland visibility metrics (p > 0.217). CONCLUSIONS: The proposed method can assess meibomian gland visibility in an objective and repeatable way. Scleral lens wear appears to not adversely affect meibomian gland drop-out and visibility while might improve dry eye symptoms after one year of lens wear. These preliminary results should be confirmed with a control group.

Tear film layers and meibomian gland assessment in patients with type 1 diabetes mellitus using a noninvasive ocular surface analyzer: a cross-sectional case-control study.

PURPOSE: To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM). METHODS: Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer's I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested. RESULTS: The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups. CONCLUSION: Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations.

Assessment of Meibomian Gland (MD) Impairment Among Seasonal Allergic Conjunctivitis (SAC) Patients.

BACKGROUND Allergic conjunctivitis, one of the frequently occurring ocular surface diseases, can cause mucus discharge, itchy sensation, conjunctival hyperemia, and papillary formation. Seasonal allergic conjunctivitis (SAC) is associated with xerophthalmia and instability of tear film. Meibomian gland (MG) can secrete lipids to avoid xerophthalmia. However, there have been few reports on MG morphological alterations of SAC patients. This study aimed to examine the morphological alterations of MG among SAC patients. MATERIAL AND METHODS Our study included 89 eyes from 89 patients with SAC and 112 eyes of healthy volunteers. The symptoms were assessed by ocular surface disease index (OSDI) questionnaire. Then, the tests shown below were carried out, including tear evaporation rate from the ocular surface (TEROS), slit-lamp examination, break-up time (BUT) of tear film, Schirmer test I, vital staining, meibography, and meibum expression grading. MG was examined with laser scanning confocal microscopy (LSCM). RESULTS Relative to the control group, the OSDI was significantly higher in the SAC group. TEROS values, BUT, vital staining, MG expression, MG distortion rates, and MG dropout grades were significantly worse in the SAC group compared with the control group. As suggested by LSCM, SAC patients had markedly worse averages of parameters compared with controls. CONCLUSIONS The patients with SAC have more significant morphological and cytological changes in the MG. The Keratograph 5M system and LSCM are effective methods for evaluating MG status and ocular surface diseases.

Tear film interferometry assessment after intense pulsed light in dry eye disease: A randomized, single masked, sham-controlled study.

BACKGROUND: Inadequate meibomian glands (MGs) secretion can lead to dry eye signs and symptoms. Tear film lipid layer (TFLL) secreted by MGs protects and prevents rapid evaporation of tear film. The purpose was to assess TFLL alteration and function in patients with evaporative dry eye (EDE) using tear interferometry after optimal pulse light technology (OPT) intense pulsed light (IPL). METHODS: This prospective randomized examiner-masked sham- controlled study included 86 participants (142 eyes) with DED. IPL or sham procedure was performed on day 0, 21, and 42. Ocular Surface Disease Index (OSDI), non-invasive breakup time (NITBUT), interferometric fringe pattern determined TFLL quality, fluorescein staining (FS), and meibum gland (MG) were assessed at day 0, 21, 42 and 3-month. RESULTS: At 3-month, TFLL, NITBUT, MG drop-out, MG quality, MG expressibility, FS and OSDI improved significantly (P < 0.05) in the IPL group, while the sham group had no significant improvements. Except for Meibo-score and FS, all parameters significantly correlated with the improvement in TFLL following IPL treatment. Additionally, artificial tears usage was significantly less in the IPL group from D-42 onwards. CONCLUSION: IPL treatment demonstrated the ability to improve TFLL quality and clinically reduced sign and symptoms of DED thereby reducing the frequency of artificial tears use.

Evaluation of the Repeatability of the LacryDiag Ocular Surface Analyzer for Assessment of the Meibomian Glands and Tear Film.

Purpose: This study aimed to determine the intra- and interobserver repeatability of the new LacryDiag Ocular Surface Analyzer and compare it to a similar all-in-one device, the OCULUS Keratograph 5M. Methods: Thirty healthy subjects aged 18 years and above were recruited for this study. All patients were free of any existing ocular pathology. The LacryDiag Ocular Surface Analyzer was used to evaluate tear meniscus height, interferometry, noninvasive tear break-up time (NIBUT), and meibography. The same or analogous exams were performed using the OCULUS Keratograph 5M. Test equivalation was used to compare data from corresponding examinations. Paired t-tests and coefficient of variation were used to determine inter- and intraobserver repeatability. Bland-Altman analysis was used to determine level of agreement between devices. Results: There were no differences in mean values for tear meniscus height, NIBUT, or tear film interferometry between observers for either device. Significant differences were found between observers for meibography when using the LacryDiag (P = 0.008 for percent loss calculation and P = 0.004 for grading scale). Intra-observer variability for NIBUT was significantly higher for the Keratograph (P = 0.0003 for observer A and P < 0.0001 for observer B). Conclusions: There was a good correlation but poor agreement between devices for a given observer. This was likely influenced by the use of repeated testing and the non-dry eye cohort. Translational Relevance: Both the repeatability of the testing device and the use of multiple outcome measures are essential for the diagnosis and monitoring of patients with dry eye disease (DED).

In vivo confocal microscopy assessment of meibomian glands microstructure in patients with Graves' orbitopathy.

BACKGROUND: To evaluate microstructural changes in the meibomian glands (MGs) in patients with active and inactive Graves' orbitopathy (GO), using in vivo confocal microscopy (IVCM), and to investigate the correlations between clinical and confocal findings. METHODS: Forty patients (80 eyes) with GO (34 eyes with active GO, 46 eyes with inactive GO), and 31 age- and sex-matched control participants (62 eyes) were enrolled consecutively. A researcher recorded the clinical activity score (CAS) for each patient. A complete ophthalmic examination was then performed, including external eye, ocular surface and MGs. IVCM of the MGs was performed to determine the MG acinar density (MAD), MG longest and shortest diameters (MALD and MASD), MG orifice area (MOA), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), acinar wall inhomogeneity (AWI), acinar periglandular interstices inhomogeneity (API), and severity of MG fibrosis (MF). RESULTS: All confocal microscopy assessments of MGs significantly differed among groups (all P = 0.000). Compared to controls, GO groups showed lower MOA (1985.82 ± 1325.30 µm2 in active GO and 2021.59 ± 1367.45 µm2 in inactive GO vs. 3896.63 ± 891.90 µm2 in controls, all P = 0.000) and MAD (87.21 ± 32.69 /mm2 in active GO and 80.72 ± 35.54 /mm2 in inactive GO vs. 114.69 ± 34.90 /mm2 in controls, P = 0.001 and 0.000, respectively); greater MALD (118.11 ± 30.23 µm in active GO and 120.58 ± 27.64 µm in inactive GO vs. 58.68 ± 20.28 µm in controls, all P = 0.000) and MASD (44.77 ± 19.16 µm in active GO and 46.02 ± 20.70 µm in inactive GO vs. 27.80 ± 9.90 µm in controls, all P = 0.000); and higher degrees of MAI, MSR, and MF (all P<0.05). Eyes with active GO had higher degrees of MAI (P = 0.015), AWI (P = 0.000), and API (P = 0.000), while eyes with inactive GO had higher degrees of MSR (P = 0.000) and MF (P = 0.017). In GO groups, AWI and API were positively correlated with CAS (r = 0.640, P = 0.000; r = 0.683, P = 0.000, respectively), and MF was negatively correlated with CAS (r = - 0.228, P = 0.042). CONCLUSIONS: IVCM effectively revealed microstructural changes of MGs in eyes with GO and provided strong in vivo evidence for the roles of obstruction and inflammation in the ocular surface disease process. Furthermore, it revealed discernible patterns of MG abnormalities in eyes with active GO and inactive GO, which are not easily distinguishable by typical clinical examinations.

Deep learning-based automatic meibomian gland segmentation and morphology assessment in infrared meibography.

Meibomian glands (MG) are large sebaceous glands located below the tarsal conjunctiva and the abnormalities of these glands cause Meibomian gland dysfunction (MGD) which is responsible for evaporative dry eye disease (DED). Accurate MG segmentation is a key prerequisite for automated imaging based MGD related DED diagnosis. However, Automatic MG segmentation in infrared meibography is a challenging task due to image artifacts. A deep learning-based MG segmentation has been proposed which directly learns MG features from the training image dataset without any image pre-processing. The model is trained and evaluated using 728 anonymized clinical meibography images. Additionally, automatic MG morphometric parameters, gland number, length, width, and tortuosity assessment were proposed. The average precision, recall, and F1 score were achieved 83%, 81%, and 84% respectively on the testing dataset with AUC value of 0.96 based on ROC curve and dice coefficient of 84%. Single image segmentation and morphometric parameter evaluation took on average 1.33 s. To the best of our knowledge, this is the first time that a validated deep learning-based approach is applied in MG segmentation and evaluation for both upper and lower eyelids.

Meibomian glands visibility assessment through a new quantitative method.

PURPOSE: The aim of this study is to develop a new objective semiautomatic method for analysing Meibomian glands visibility quantitatively. METHODS: One hundred twelve healthy volunteers aged between 18 and 90 years (48.29 ± 27.46 years) participated in this study. Infrared meibography was obtained from the right upper eyelid through Oculus Keratograph 5 M. Meibographies were classified into 3 groups: Group 1 = patients with good subjective glands visibility and a gland dropout percentage < 1/3 of the total Meibomian gland area; Group 2 = patients with low subjective glands visibility and a gland dropout < 1/3; and Group 3 = patients with low subjective glands visibility and a gland dropout > 1/3. New metrics based on the visibility of the Meibomian glands were calculated and later compared between groups. Rho Spearman test was used to assess the correlation between each metric, and Meibomian gland dropout percentage with the entire sample and after excluding Group 2. A p value less than 0.05 was defined as statistically significant. RESULTS: Fifty-six subjects were classified in Group 1 (24.48 ± 9.62 years), 19 in Group 2 (69.16 ± 21.30 years) and 37 in Group 3 (73.59 ± 13.70 years). No statistically significant differences were found between Groups 1 and 2 in dropout percentage. All metrics, with the exception of entropy, showed a higher Meibomian gland visibility in Group 1 than in the other two groups. Moderate correlations were statistically significant for all metrics with the exception of entropy. Correlations were higher after excluding Group 2. CONCLUSION: The proposed method is able to assess Meibomian gland visibility in an objective and repeatable way, which might help clinicians enhance Meibomian gland dysfunction diagnosis and follow-up treatment.

Clinical characteristics of dry eye with ocular neuropathic pain features: comparison according to the types of sensitization based on the Ocular Pain Assessment Survey.

BACKGROUND: To compare the clinical characteristics of dry eye patients with ocular neuropathic pain features according to the types of sensitization based on the Ocular Pain Assessment Survey (OPAS). METHODS: Cross-sectional study of 33 patients with dry eye and ocular neuropathic pain features. All patients had a comprehensive ophthalmic assessment including detailed history, the intensity and duration of ocular pain, the tear film, ocular surface, and Meibomian gland examination, and OPAS. Patients with < 50% improvement in pain intensity after proparacaine challenge test were assigned to the central-dominant sensitization group (central group) and those with ≥50% improvement were assigned to the peripheral-dominant sensitization group (peripheral group). All variables were compared between the two groups. RESULTS: No significant differences were observed in age, sex, underlying diseases, history of ocular surgery, duration of ocular pain, tear film, ocular surface and Meibomian gland parameters (all p > 0.05). Ocular pain and non-ocular pain severity and the percentage of time spent thinking about non-ocular pain were significantly higher in the central group than in the peripheral group (all p < 0.05). Central group complained more commonly of a burning sensation than did the peripheral group (p = 0.01). CONCLUSIONS: Patients with central-dominant sensitization may experience more intense ocular and non-ocular pain than the others and burning sensation may be a key symptom in those patients.

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.

Association of meibomian gland morphology with symptoms and signs of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

PURPOSE: To describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology. METHODS: Cross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex. RESULTS: Among 268 patients, no MG features were associated with symptom scores (p > 0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and ≥ 3.2 s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p = 0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p = 0.02). Longer Schirmer test wetting lengths (0-5, >5-10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p = 0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p = 0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p = 0.006) in the upper lid. CONCLUSION: In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.

Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.