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.

Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients.

Menthol is thought to stimulate lacrimation via activation of cold-sensitive primary afferent neurons in the cornea. We evaluated a warm compress containing menthol as a potential treatment for dry eye by examining its effects on the tear film in healthy subjects (n = 20) and dry eye patients (n = 35). Disposable eyelid-warming steamers that either did (MH) or did not (HO) contain menthol were applied to one eye of each subject either once only for 10 min or repeatedly over 2 weeks. Single application of MH significantly increased tear meniscus volume (P = 8.6 × 10-5, P = 1.3 × 10-5) and tear film breakup time (P = 0.006, P = 0.002) as well as improved meibum condition in healthy subjects and dry eye patients, respectively. Repeated application of MH significantly increased tear meniscus volume (P = 0.004, P = 1.7 × 10-4) and tear film breakup time (P = 0.037, P = 0.010) in healthy subjects and dry eye patients, respectively. Repeated application of MH thus induced persistent increases in tear fluid volume and tear film stability in dry eye patients, suggesting that repeated use of a warm compress containing menthol is a potential novel treatment for dry eye disease.

Tear Interferometric Patterns Reflect Clinical Tear Dynamics in Dry Eye Patients.

PURPOSE: We investigated whether the tear interferometric pattern was able to identify differences in tear film kinetics among clinical subtypes of dry eye. METHODS: A total of 138 eyes of 76 subjects (38 men and 38 women; mean age ± SD, 61.6 ± 16.2 years) with or without dry eye who visited Itoh Clinic from May to August 2015 were enrolled in a cross-sectional study. Clinical diagnosis of dry eye subtype was based on tear film parameters. The pattern of tear film kinetics determined by interferometry was classified as 0 (monotonous gray or multicolor interferometric fringe with a noninvasive breakup time [NIBUT] of ≥5 seconds), 1 (multicolor interferometric fringe with a NIBUT of <5 seconds), or 2 (grayish amorphous interferometric fringe with a NIBUT of <5 seconds), and reliability of classification was evaluated. Lipid layer thickness (LLT) for the tear film was also determined by interferometry. RESULTS: Interrater κ values for evaluation of interferometric patterns ranged from 0.57 to 0.94 for both physicians and nonphysicians with reference to a dry eye expert, the latter of whom showed an intrarater reliability of 0.90. The distribution of eyes among interferometric patterns 0, 1, and 2 coincided well with the clinical subgroups of normal tear condition, non-Sjögren syndrome aqueous-deficient dry eye, and meibomian gland dysfunction, respectively. A multicolor interferometric fringe was essentially observed only at an LLT of >70 nm. CONCLUSIONS: Tear interferometry was able to reliably distinguish clinical subtypes of dry eye by reflecting the balance between the lipid and aqueous layers of the tear film.

A newly developed noninvasive and mobile pen-shaped meibography system.

PURPOSE: To examine the usefulness of a newly developed noninvasive mobile pen-shaped meibography system. METHODS: This study evaluated a newly developed noninvasive mobile pen-shaped meibography system comprising an infrared light-emitting diode as the light source and a highly sensitive complementary metal oxide semiconductor image camera. The images were recorded digitally. The utility of this system was compared with that of the previously developed noncontact infrared meibography system for examination of the upper and lower eyelids in 20 healthy volunteers (range, 2-91 years) and 23 patients with meibomian gland dysfunction, 17 patients with dry eyes who wore contact lenses, and 14 patients with allergic conjunctivitis accompanied by itching. RESULTS: Using the newly developed noninvasive mobile pen-shaped meibography system, clear images of the meibomian glands were obtained in all age groups. The quality of the images obtained was similar between the two meibography systems. The quantitative analysis of the images obtained showed no statistically significant difference between the two meibography systems. CONCLUSIONS: The newly developed noninvasive mobile pen-shaped meibography system is a useful tool that provides meibomian gland images of the same quality and quantity as the noncontact meibography system equipped with a slit lamp. This new system is convenient and applicable for examination of meibomian glands in patients of all ages.

Comparison of the long-term effects of various topical antiglaucoma medications on meibomian glands.

PURPOSE: To examine the effects of long-term antiglaucoma eye drop treatment on meibomian glands. METHODS: The subjects were 71 eyes of 71 glaucoma patients (group 1) receiving one type of antiglaucoma eye drops, 61 eyes of 61 glaucoma patients (group 2) receiving two types of antiglaucoma eye drops, and 30 eyes of 30 glaucoma patients (group 3) receiving three types of antiglaucoma eye drops. Controls comprised 75 eyes of 75 healthy volunteers. Subjective symptoms were evaluated by questionnaire, and lid margin and superficial punctate keratopathy were evaluated by slit lamp examination. Meibomian glands of upper and lower eyelids were observed and scored using noncontact meibography (meiboscore). Tear film break-up time (BUT) was measured and meibum was graded. RESULTS: Lid margin abnormality, superficial punctate keratopathy, meiboscore, and meibum scores were significantly higher in glaucoma patients than in controls (P < 0.001). BUT and Schirmer scores were significantly lower in glaucoma patients than in controls (P < 0.001). Subgroup analysis of the parameters in group 1 revealed no significant difference between patients receiving prostaglandin and those receiving ß-blockers, or among groups 1, 2, and 3. Multivariate regression analysis demonstrated that meiboscore significantly correlated with lid margin abnormality score (P = 0.007) and BUT (P = 0.045) in group 1; with BUT (P = 0.004), symptom score (P = 0.003), and age (P = 0.026) in group 2; and with lid margin abnormality score (P = 0.001) in group 3. CONCLUSIONS: Long-term use of antiglaucoma eye drops was associated with alterations in meibomian gland morphology and function.

Effects of long-term topical anti-glaucoma medications on meibomian glands.

OBJECTIVE: To examine effects of long-term topical anti-glaucoma medications on meibomian gland morphology and function and assess their relationship with slit-lamp findings. METHODS: This was a cross-sectional observational case series of 31 patients with glaucoma (mean age ± standard deviation, 65.0 ± 13.0 years; mean duration of eye drop use, 7.9 ± 6.0 years) treated with topical anti-glaucoma drugs in only one eye for more than 1 year: 13 receiving prostaglandin analogues (PGs) alone, eight receiving ß-blockers alone, and ten receiving multiple treatments. Untreated contralateral eyes served as controls. Lid margin (lid margin abnormality score: 0-4) and superficial punctate keratopathy (SPK score: 0-1) were observed with a slit lamp. Upper and lower eyelids were turned over to observe meibomian glands using non-contact meibography. Meibomian gland loss was scored for each eyelid from grade 0 (no loss of meibomian glands) through grade 3 (loss >2/3 of total meibomian gland area). Meibomian lipid content (meibum) was scored (meibum score: 0-3). RESULTS: Treated eyes had significantly higher scores for lid margin abnormality (P= 0.001), SPK (P< 0.001), meibo-score (P< 0.001), and meibum (P< 0.001) than control eyes. Tear film break-up time (BUT) was significantly shorter in treated eyes than in control eyes (P= 0.001). Schirmer values were significantly lower in treated eyes than in control eyes (P= 0.0039). Subgroup analysis indicated a significantly higher meibo-score in eyes treated with PGs (P= 0.0046) and in eyes treated with ß-blockers (P= 0.0231) than in the corresponding controls. CONCLUSIONS: Long-term anti-glaucoma eye drop use affects meibomian gland morphology and function.

Association of contact lens-related allergic conjunctivitis with changes in the morphology of meibomian glands.

PURPOSE: To observe morphological changes in the meibomian glands of patients with contact lens-related allergic conjunctivitis (CLAC) and to assess the relations between the morphological changes and eyelid and tear film parameters. METHODS: We observed subjects in four groups: 64 eyes of 64 contact lens (CL) wearers with CLAC, 77 eyes of 77 CL wearers without CLAC, 55 eyes of 55 patients with perennial allergic conjunctivitis (perennial AC), and 47 eyes of 47 healthy volunteers. The following tests were performed: slit-lamp examination, measurement of tear film breakup time, grading of morphological changes in meibomian glands (meiboscore) as assessed by noncontact meibography, grading of meibomian gland distortion in meibography, tear production as assessed by Schirmer's I test, and grading of meibum expression. RESULTS: The mean score for meibomian gland distortion was significantly higher in the CL wearers with CLAC than in the CL wearers without CLAC (p < 0.0001); it was also significantly higher in the non-CL wearers with perennial AC than in the non-CL wearers without perennial AC (p < 0.0001). There was no significant difference between the mean scores for meibomian gland distortion of the non-CL wearers with perennial AC and the CL wearers with CLAC (p = 0.27). The score for meibomian gland distortion was significantly positively correlated with the meibum score in the CL wearers with CLAC and with the meiboscore in the CL wearers without CLAC. CONCLUSION: CLAC is associated with an increase in meibomian gland distortion. Allergic reaction, rather than CL wear, appears to be responsible for the increase in meibomian gland distortion in patients with CLAC.

Efficacy of diagnostic criteria for the differential diagnosis between obstructive meibomian gland dysfunction and aqueous deficiency dry eye.

PURPOSE: To evaluate diagnostic criteria for obstructive meibomian gland dysfunction (MGD) using three parameters (symptom score, lid margin abnormality score, and meibomian gland morphologic change scores) for differentiating obstructive MGD from aqueous deficiency dry eye (ADDE). METHODS: Twenty-five eyes of 25 patients (mean age, 66.6 years) diagnosed with obstructive MGD and 15 eyes of 15 patients (mean age, 61.3 years) diagnosed with ADDE were analyzed. Ocular symptoms were scored from 0 to 14 according to the number of symptoms. Lid margin abnormality was scored from 0 to 4 according to the number of abnormalities. Meibomian gland changes were scored from 0 to 6 using noncontact meibography (meibo-score). Superficial punctate keratopathy was scored from 0 to 3. Meibum was graded from 0 to 3 according to volume and quality. Tear film break-up time was measured consecutively three times after instillation of fluorescein, and the median value was adopted. Tear film production was evaluated using the Schirmer test. RESULTS: Ocular symptom and lid margin abnormality scores and tear film break-up time did not differ significantly between the obstructive MGD and ADDE groups. The meibum score and meibo-score were significantly higher in the obstructive MGD group than in the ADDE group. The Schirmer value was significantly lower in the ADDE group than in the obstructive MGD group. When obstructive MGD was diagnosed on the basis of three scores (ocular symptom score, lid margin abnormality score, and meibo-score) all being abnormal, the sensitivity and specificity for differentiating between obstructive MGD and ADDE were 68.0% and 80%, respectively. CONCLUSIONS: Although the criteria were moderately reliable for differentiating patients with obstructive MGD from those with ADDE when the diagnosis of obstructive MGD was made on the basis of three abnormal scores, they do not provide comprehensive diagnostic tools for differentiating MGD, ADDE, and healthy individuals. We need to add other parameters such as the Schirmer test value and the meibum score to the diagnostic criteria to enhance their reliability for differentiating MGD and ADDE.

Proposed diagnostic criteria for seborrheic meibomian gland dysfunction.

PURPOSE: To compare clinical findings between patients with seborrheic meibomian gland dysfunction (MGD) and normal controls and to propose diagnostic criteria for seborrheic MGD. METHODS: Thirty eyes of 30 patients [13 men and 17 women; age (mean +/- SD) 73.9 +/- 9.9 years] diagnosed with seborrheic MGD and 60 eyes of 60 healthy volunteers (22 men and 38 women; age: 71.0 +/- 9.3 years) as a control group were included in this study. Ocular symptoms were scored from 0 to 14 according to the number of symptoms present. Lid margin abnormality was scored from 0 to 4 depending on the number of abnormalities present. Meibomian gland changes were scored from 0 to 6 on the basis of noncontact meibography (meiboscore). Superficial punctate keratopathy was scored from 0 to 3. Tear film production was evaluated by Schirmer test. Receiver operating characteristic curves with calculations of the area under the curve were used to describe the accuracy of each parameter to differentiate patients with seborrheic MGD from normal eyes. RESULTS: Ocular symptom score and lid margin abnormality score were significantly higher in the seborrheic MGD group than in the control group (P < 0.0001 for both scores). Area under the curve values indicated that the lid margin abnormality score had the highest diagnostic power as a single parameter followed by the ocular symptom score. When the diagnosis for seborrheic MGD was made on the basis of the 2 scores (ocular symptom score and lid margin abnormality score) being abnormal, the sensitivity was 100% and the specificity was 98.3%. CONCLUSIONS: On the basis of these findings, we recommend that physicians use ocular symptom score and lid margin abnormality score in the diagnosis of seborrheic MGD. Seborrheic MGD should be considered very likely when both of the 2 scores are abnormal.

Meibomian gland duct distortion in patients with perennial allergic conjunctivitis.

PURPOSE: To observe morphologic changes of meibomian glands in patients with and without perennial allergic conjunctivitis (AC) and to assess the relation between morphologic changes of the meibomian glands of both eyelids and tear film parameters. METHODS: In this study, 55 eyes of 55 patients with perennial AC and 47 eyes of 47 healthy volunteers as controls were included. The following tests were performed: a slit-lamp examination, measurement of tear film breakup time, grading of meibomian gland morphologic changes (meibography score) assessed with a noncontact meibography, meibomian gland duct distortion in meibography, tear production by the Schirmer I test, and grading of meibum expression. RESULTS: The frequency of meibomian gland duct distortion was significantly greater in patients with AC (45%) than that in controls (8.5%; P < 0.0001). The meibum (P = 0.049) and superficial punctate keratopathy scores (P = 0.0076) were significantly higher in patients with AC than those in controls. There was no significant difference in meibography score, breakup time, or Schirmer value between the 2 groups. The meibomian expression score was significantly higher in patients with AC with meibomian gland duct distortion than in patients with AC without meibomian gland duct distortion (P = 0.0012). CONCLUSION: Perennial AC is associated with increased meibomian gland duct distortion.

Proposed diagnostic criteria for obstructive meibomian gland dysfunction.

PURPOSE: To compare clinical findings between patients with obstructive meibomian gland dysfunction (MGD) and normal controls and to propose diagnostic criteria for obstructive MGD. DESIGN: Cross-sectional, observational case series. PARTICIPANTS: Fifty-three eyes of 53 patients (18 men, 35 women; age [mean +/- standard deviation] 71.4 +/- 10.0 years) who were diagnosed with obstructive MGD and 60 eyes of 60 healthy volunteers (22 men, 38 women; 71.0 +/- 9.3 years) as a control group. METHODS: Ocular symptoms were scored from 0 to 14 according to the number of existing symptoms. Lid margin abnormality was scored from 0 to 4 depending on the number of existing abnormalities. Meibomian gland changes were scored from 0 to 6 based on noncontact meibography (meibo-score). Superficial punctuate keratopathy (SPK) was scored from 0 to 3. Meibum was graded from 0 to 3 depending on the volume and quality. Tear film production was evaluated by Schirmer's test. Receiver operating characteristic curves with calculations of area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate obstructive MGD from normal eyes. MAIN OUTCOME MEASURES: Ocular symptom score, lid margin abnormality score, meibo-score, meibum score, SPK score, tear film breakup time (BUT), and the Schirmer value. RESULTS: Ocular symptom score, lid margin abnormality score, meibo-score, meibum score, and SPK score were significantly higher in the obstructive MGD group than in the control group (P<0.0001 for all scores). The BUT was significantly shorter in the obstructive MGD group than in the control group (P<0.0001). The AUC values indicated that the ocular symptom score had the highest diagnostic power as a single parameter, followed by the lid margin abnormality score, meibo-score, and BUT. CONCLUSIONS: Based on these findings, we recommend that physicians use the ocular symptom score, lid margin abnormality score, and meibo-score to diagnose MGD. Obstructive MGD should be suspected when any 2 of the 3 scores are abnormal. Obstructive MGD is very likely when all 3 scores are abnormal.

Contact lens wear is associated with decrease of meibomian glands.

PURPOSE: Approximately 30% to 50% of contact lens (CL) wearers report dry eye symptoms. Meibomian gland dysfunction has been recognized as a possible cause of CL-related dry eye. This study investigated the influence of CL wear on the meibomian glands using a newly developed meibographic technique. DESIGN: Cross-sectional observational case series. PARTICIPANTS: Contact lens wearers (n=121; 47 men, 74 women; mean age+/-standard deviation, 31.8+/-8.0 years) and healthy volunteers (n=137; 71 men, 66 women; mean age+/-standard deviation, 31.4+/-15.1 years). METHODS: The following tests were performed: slit-lamp examinations of the eyelids, corneal and conjunctival staining using fluorescein, measurement of the tear film breakup time, evaluation of the meibomian glands using noncontact meibography, and measurement of tear production using the Schirmer I test. Partial or complete loss of the meibomian glands was scored for each eyelid using 4 grades (meiboscores): grade 0 (no loss of meibomian glands) through grade 3 (the area characterized by gland dropout was more than 66% of the total area containing the meibomian glands). The meiboscores for the upper and lower eyelids were summed for each subject. MAIN OUTCOME MEASURES: Score of meibomian gland changes (meiboscore), tear film breakup time, and Schirmer test value. RESULTS: The meiboscore was significantly higher (P<0.0001) in CL wearers (mean, 1.72; 95% confidence interval, 1.47-1.96) than in the control group (mean, 0.96; 95% confidence interval, 0.73-1.19). The average meiboscore of CL wearers was similar to that of a 60- to 69-year-old age group from the normal population. A significant positive correlation was observed between the duration of CL wear and the meiboscore. CONCLUSIONS: Contact lens wear is associated with a decrease in the number of functional meibomian glands. This decrease is proportional to the duration of CL wear.

Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population.

PURPOSE: To examine the morphologic changes in meibomian glands associated with aging and gender using a novel meibography system and to assess their relation with slit-lamp findings regarding eyelid and tear film function in a normal population. DESIGN: Cross-sectional observation case series. PARTICIPANTS: Two hundred thirty-six healthy volunteers (114 men, 122 women; mean age+/-standard deviation, 41.2+/-23.1 years; range, 4-98 years). METHODS: The upper and lower eyelids were turned over and the meibomian glands were observed using the noncontact meibography system, which consisted of a slit lamp equipped with an infrared charge-coupled device video camera and an infrared transmitting filter. A transilluminating light probe was not necessary. Partial or complete loss of the meibomian glands was scored for each eyelid from grade 0 (no loss of meibomian glands) through grade 3 (the lost area was more than two thirds of the total meibomian gland area). The tear film break-up time (BUT) was measured and tear film production was evaluated by Schirmer test. MAIN OUTCOME MEASURES: Score of meibomian gland changes (meiboscore), tear film BUT, and Schirmer test value. RESULTS: Using the meibography system, clear images of the meibomian glands were obtained in all subjects, including children. There were significant positive correlations between age and meiboscore in the entire subject population (R = 0.428; P<0.0001), as well as in males (R = 0.462; P<0.0001) and females (R = 0.418; P<0.0001). There were significant negative correlations between age and tear film BUT (R = -0.153; P = 0.019) and the Schirmer test value (R = -0.289; P<0.0001). The meiboscore was significantly positively correlated with the lid margin abnormality score (R = 0.359; P<0.0001). CONCLUSIONS: The noncontact meibography system is a useful, quick, and patient-friendly method for obtaining information on the meibomian gland structure. Using this method, the authors found that changes in meibomian glands increase with age.