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.

Temporal variations in meibomian gland structure-A pilot study.

PURPOSE: To investigate whether there is a measurable change in meibomian gland morphological characteristics over the course of a day (12 h) and over a month. METHODS: The study enrolled 15 participants who attended a total of 11 study visits spanning a 5-week period. To assess diurnal changes in meibomian glands, seven visits were conducted on a single day, each 2 h apart. For monthly assessment, participants attended an additional visit at the same time of the day every week for three consecutive weeks. Meibography using the LipiView® II system was performed at each visit, and meibomian gland morphological parameters were calculated using custom semi-automated software. Specifically, six central glands were analysed for gland length ratio, gland width, gland area, gland intensity and gland tortuosity. RESULTS: The average meibomian gland morphological metrics did not exhibit significant changes during the course of a day or over a month. Nonetheless, certain individual gland metrics demonstrated notable variation over time, both diurnally and monthly. Specifically, meibomian gland length ratio, area, width and tortuosity exhibited significant changes both diurnally and monthly when assessed on a gland-by-gland basis. CONCLUSIONS: Meibomian glands demonstrated measurable structural change over short periods of time (hours and days). These results have implications for innovation in gland imaging and for developing precision monitoring of gland structure to assess meibomian gland health more accurately.

Morphological Changes of Meibomian Glands in Men With Benign Prostate Hyperplasia.

PURPOSE: Meibomian glands are subject to regulation by sex hormones. We have now investigated the possible relation between benign prostate hyperplasia (BPH) and meibomian gland dysfunction (MGD). METHODS: Men diagnosed with BPH and receiving treatment with tamsulosin and age-matched male control subjects who attended Itoh Clinic, Saitama, Japan, were enrolled. An ocular symptom score, lid margin abnormality score, and superficial punctate keratopathy score as well as the meiboscore (0-6), meibum grade, breakup time of the tear film, and Schirmer test values were evaluated. Male pattern baldness was also graded according to the Hamilton-Norwood scale. RESULTS: Forty-four eyes of 44 men with BPH (mean age ± SD, 76.1 ± 2.2 years) and 46 eyes of 46 control subjects (mean age ± SD, 75.3 ± 6.2 years) were enrolled. The meiboscore in the BPH group (4.5 ± 1.4) was significantly higher than that in the control group (1.8 ± 1.5, P < 0.0001). Breakup time of the tear film was significantly shorter (3.6 ± 1.7 vs. 5.6 ± 2.5 seconds, P < 0.0001), and Schirmer test value was significantly smaller (9.8 ± 4.8 vs. 13.3 ± 8.0 mm, P = 0.048) in the BPH group than that in the control group. Other ocular parameters did not differ significantly between the 2 groups. The proportion of men with androgenic alopecia was also higher in the BPH group than that in the control group. CONCLUSIONS: BPH was associated with meibomian gland loss and instability of the tear film as well as with the presence of androgenic alopecia.

In Vivo Confocal Microscopy Morphometric Analysis of Meibomian Glands in Patients With Graves Ophthalmopathy.

PURPOSE: To characterize meibomian glands (MGs) features in patients with Graves ophthalmopathy (GO) by in vivo confocal microscopy (IVCM) and to further investigate possible correlations with ocular surface characteristics. METHODS: Consecutive patients with GO and controls were enrolled. The following ocular surface parameters were measured: tear break-up time, Schirmer test, and corneal fluorescein staining (Oxford score) were performed on each subject. IVCM of MGs was performed, and the scans were analyzed with ImageJ software for the calculation of the following: acinar unit density, total gland area, total lumen area (TLA), acinar longest diameter, and acinar shortest diameter. A nonparametric Mann-Whitney U test was used to compare variables between patients with GO and controls. The Spearman correlation analysis was used to evaluate the correlations between ocular surface and IVCM parameters. RESULTS: Twenty-one patients with GO and 24 sex- and age-matched healthy controls were included. Acinar unit density was significantly lower in patients with GO compared with controls (24.5 ± 8.1 vs. 34.2 ± 7.5 U/mm; P < 0.001). In addition, patients with GO showed significantly higher values of TLA, acinar longest diameter, and acinar shortest diameter compared with controls (respectively, 3104.7 ± 1713.3 vs. 1393.8 ± 448.0 µm, 94.4 ± 21.2 vs. 64.3 ± 10.1 µm and 56.6 ± 15.3 vs. 42.2 ± 12.3 µm; always P < 0.05). In patients with GO, TLA showed a significant inverse correlation with Schirmer test (Rs = -0.467; P = 0.038). CONCLUSIONS: IVCM allowed to detect distinctive features of MGs in patients with GO and could represent a surrogate tool for the assessment of MG status in these patients.

Effect of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Inhibitors on the Meibomian Gland Morphology in Patients with Dyslipidemia.

PURPOSE: Previous studies have suggested an association between dyslipidemia and meibomian gland dysfunction (MGD). The aim of this prospective, nonrandomized clinical study is to evaluate the possible association of dyslipidemia and its treatment with meibomian gland (MG) morphologic changes by standardized meibography. DESIGN: Prospective, nonrandomized clinical study. METHODS: Two groups of participants were enrolled: group 1, comprised of patients under regular 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment for dyslipidemia, and group 2, those with newly diagnosed dyslipidemia who were under lifestyle interventions. Meibography was performed at baseline and at both the 6- and 12-month visits and were graded by meiboscores. Participants underwent slit lamp examination for signs of changes in meibum quality and MG lid morphologic features. The Ocular Surface Disease Index questionnaire was given to measure subjective symptoms of ocular surface disease. Dry eye parameters including tear meniscus height, noninvasive first and average tear film break-up time, and Schirmer test results were also recorded. RESULTS: Ninety-eight participants completed this longitudinal study over 12 months. There were statistically significant changes in total meiboscores (P = .01) and upper eyelid meiboscores (P = .012), lid margin abnormality scores (P = .0059), and meibum quality (P = .0002) in the statin group during follow-up visits. Similar changes of upper eyelid meiboscores (P = .046) and meibum quality (P = .046) were noted in the nonstatin group. CONCLUSION: Meibomian gland atrophy and deterioration of meibum quality continued in the long term among participants with dyslipidemia even under statin usage.

Evaluating Dry Eye and Meibomian Gland Dysfunction With Meibography in Patients With Stevens-Johnson Syndrome.

PURPOSE: To investigate ocular surface and meibomian gland characteristics using infrared meibography in patients with Stevens-Johnson syndrome (SJS). METHODS: This is a single-center, prospective, noncontrolled, observational study. Thirty-two Thai patients (64 eyes) with SJS for 1 year or longer (1-44 years) were enrolled in the study. All participants underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy, tear meniscus height, fluorescein tear breakup time, ocular surface fluorescein staining, eyelid morphology, Schirmer 1 test, meibomian gland expressibility, and upper and lower eyelid meibography using a noncontact infrared meibograph mounted on a slit-lamp biomicroscope. RESULTS: The mean age was 42.2 ± 17.7 years (range, 4-68 years). Twenty-nine patients (90.6%) had a history of severe ocular complications in the acute stage of the disease. Medications were the most common cause of SJS (93.8%). Meibum quality could not be assessed in 23 patients (71.9%) due to no glands expressible. Partial or complete loss of the meibomian glands in either the upper or lower eyelid was found in all patients. The degree of meibomian gland dropout significantly correlated with tear breakup time (P < 0.001), meibum quality (P < 0.001), meibum expressibility (P < 0.001), ocular surface staining (P < 0.001), and presence of long-term ocular sequelae including symblepharon (P = 0.027) and limbal stem cell deficiency (P = 0.003). CONCLUSIONS: SJS is associated with obstructive meibomian gland dysfunction. The severity of meibomian gland dropout has a relationship with abnormal dry eye tests, subjective meibomian gland evaluation, and other ocular sequelae of SJS.

Evaluation of the tear clearance rate by dacryoscintigraphy in patients with obstructive meibomian gland dysfunction.

PURPOSE: To measure tear clearance values in patients with meibomian gland dysfunction (MGD) with a dynamic nuclear medicine method, namely, dacryoscintigraphy (DSCI). METHODS: Twenty-four MGD patients and 24 healthy volunteers were examined. During DSCI one drop of a solution with 100 MBq/mL99mTc sodium pertechnetate was instilled with a micropipette into the lacrimal lake of both eyes. Measurements were performed according to a dynamic data acquisition protocol, which resulted in summed DSCI images. Data were also evaluated separately in special regions of interest (ROI), and consecutive time activity curves were created. Tear clearance (T½) values were calculated based on the activity curves. In addition, tear osmolarity measurements, tear breakup time (tBUT), and Schirmer I (STI) tests were performed prior to DSCI examination. RESULTS: The T½ values were 29.91 ± 11.61 min in MGD patients and 6.26 ± 1.5 min in healthy controls. Tear osmolarity parameters were 308 ± 9.41 mOsm/L and 288.9 ± 6.4 mOsm/L, tBUT values were 5.54 ± 2.73 s and 11.4 ± 2.7 s, while the STI test values were 6.17 ± 2.78 mm and 13.58 ± 3.8 mm, respectively. The differences were significant (p < 0.01) in all cases. CONCLUSIONS: Although the MGD patients' lacrimal drainage systems were patent their tear clearance values were significantly higher than those of healthy volunteers, which may be caused by decreased drainage of tears from the eyes towards the nasal cavity. The understanding of new features regarding the altered physico-chemical characteristics of MGD tears has been augmented by the results of this study.

The influence of meibomian gland loss on ocular surface clinical parameters.

PURPOSE: To assess the relationship between the meibomian gland loss (MGL) and relevant ocular surface clinical parameters as well as the influence of age in this relationship. METHODS: A total of 161 participants (mean age; 42±17 years) were enrolled in this study. Infrared meibography was performed using Keratograph 5M (K5M; Oculus GmbH, Wetzlar). Participants were divided into five groups according to total meiboscore and the ocular surface parameters of each MGL group were studied. In addition, the relationship between MGL and the ocular surface parameters was established including age as covariant. RESULTS: Both eyelids were taken into account since no association between the MGL from upper and lower eyelid was found (k value=0.2; p=0.3) despite they were significantly correlated (r= 0.3; p<0.001). No statistically significant differences were found in symptomatology among different MGL groups. Statistically significant differences were found among MGL groups in tear osmolarity (p=0.02), bulbar redness (p=0.04), corneal and conjunctival staining (p=0.01 and p=0.004, respectively). Despite this, only corneal staining showed a significant correlation with MGL when age was covariant (r=0.2; p=0.04). CONCLUSIONS: MGL higher than 50% seems to be accompanied by signs on the ocular surface. Furthermore, age demonstrated to be a relevant factor when assessing MGL. For this reason, future studies should compare age-matched groups in order to know the contribution of the MGL on the ocular surface and establish valid cut-off values for dry eye diagnosis.

Evaluation of dry eye disase and meibomian gland dysfunction with meibography in seborrheic dermatitis.

PURPOSE: To evaluate the dry eye disase and meibomian gland dysfunction with meibography of Seborrheic Dermatit patients. METHODS: A hundred-ten of 50 patients with Seborrheic Dermatitis (group 1) and 100 eyes of 50 healthy individuals (group 2) were enrolled in this prospective study. All subjects were performed a comprehensive ophthalmic examination including lid margin alterations and meibomian gland obstruction assessment, Ocular Surface Disease Index assessment, tear film break-up time test, corneal and conjunctival fluorescein staining assessment, Schirmer test. In addition, upper and lower lids were evaluated for meibomian gland loss with non-contact meibography. The Meibomian glands were graded from grade 0 (no loss of Meibomian glands) to grade 3 (gland loss >2/3 of the total Meibomian glands). RESULTS: The mean ages of Group 1 and Group 2 were 29.1 ± 9.1(range, 18-48) and 30.6 ± 6.3(range, 20-49) years, respectively. MGD(n = 19, %34.5), Meibium gland loss(%36.4 ± 18.1), upper meiboscore (0.7 ± 0.8), lower meiboscore(0.6 ± 0.7) and DED (n = 10, %18.2) were significantly higher in the SD patients compared with the control participants (p = 0.002, p < 0.001, p = 0.011, p = 0.005, p = 0.048, respectively). There was significant relationship between age with Meibomian gland loss, MGD and DED (p = 0.017, p = 0.004, p = 0.002, respectively). CONCLUSIONS: Seborrheic Dermatitis may influence meibomian gland morphology and as a result causing meibomian gland dysfunction and dry eye disase. For this reason, patients with Seborrheic Dermatitis should be evaluated for meibomian gland dysfunction and dry eye disase, and start treatment when needed.

In vivo confocal microscopy classification in the diagnosis of meibomian gland dysfunction.

AIM: Meibomian gland dysfunction (MGD) is one of the most common disorders in ophthalmology. The aim of this study was to evaluate the use of this in vivo confocal microscopy (IVCM)-MGD description to classify patients affected by clinical MGD and measure the correlation with standard clinical criteria and subjective symptoms. METHODS: One hundred eyes of 100 patients suffering from MGD and 15 eyes of normal subjects were included. A comprehensive evaluation with the ocular surface disease index (OSDI), Schirmer test, tear break-up time (TBUT), tear osmolarity, Oxford score, Meibomian gland expression, palpebral IVCM, and meibography was performed. Then each patient was classified using a new IVCM classification: type 0 for normality, type 1 for meibum obstruction, type 2 for inflammation, and type 3 for fibrosis. RESULTS: The mean age of patients was 52 ± 20 years old, the OSDI was 38 ± 23, the BUT 5 ± 2.6 s, the Schirmer test 13 ± 7 mm, tear osmolarity 300 ± 11 osmol/L, the Oxford score 0.5 ± 0.6, the meibum expression score 1.7 ± 1.02, and the meibography score 1.3 ± 0.9. The IVCM MG classification of the 15 normal subjects was 0. For MGD patients, 29% were in type 1, 40% were type 2, and 31% were type 3. The patients in IVCM MG type 2 had a higher OSDI (p = 0.001) compared with the other types. There was a strong correlation between the IVCM score and the meibography score (r = 0.71 p < 0.0001). CONCLUSION: This new IVCM classification provided a practical pathophysiological system for MGD. By giving objective criteria, this IVCM classification may help advance the understanding of patients' symptoms and enhance treatment effectiveness in MGD.

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.

Evaluation of Ocular Surface and Meibomian Glands Alterations with Meibography in Patients with Inactive Behçet's Uveitis.

PURPOSE: To evaluate the ocular surface and meibography of patients with inactive Behçet's uveitis. METHODS: Twenty-five right eyes of 25 patients with inactive Behçet's uveitis (Group 1) and 25 right eyes of 25 healthy individuals (Group 2) were enrolled. Detailed eye examination along with Schirmer 1 test, tear film break-up time (t-BUT), ocular surface staining with fluorescein and Oxford scoring, and ocular surface disease index (OSDI) score assessment were performed. Lower and upper eyelid Meibomian glands were examined with infrared filter of slit-lamp biomicroscope (SL-D701 with DC-4 digital camera and BG-5 background illuminator, TOPCON, Tokyo, Japan (from grade 0 (no dropout of Meibomian glands) to grade 3 (gland dropout >2/3 of the total Meibomian glands)). RESULTS: The mean ages were 36.84 ± 7.39 (range, 23-59) and 33.88 ± 8.25 (range, 18-55) in Group 1 and Group 2, respectively (p = 0.547). When compared with Group 2, in Group 1, best-corrected visual acuity (0.28 vs. 0.00 logMAR, p < 0.001), Schirmer 1 test (18.68 vs. 23.69, p = 0.017) and mean tear film break-up time (10.76 vs. 13.36, p = 0.026) were significantly lower; Oxford scale and OSDI scores were higher (p = 0.039 and p < 0.001, respectively). No significant difference in lower, upper and total (upper + lower) meiboscores were detected in between groups (p = 0.062, p = 0.228 and p = 0.152, respectively). CONCLUSION: Despite the tendency toward dry eye syndrome, Behçet's uveitis does not seem to be associated with quantitative Meibomian gland changes, which is demonstrated by gland drop-out with meibography.