Reiko Arita

The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee

Diagnostic tests of meibomian gland dysfunction (MGD) and of MGD-related disorders are based on the demonstration of abnormal anatomy and physiology of the glands and the detection of specific pathologic events. For this reason, this subcommittee report is divided into two sections. In part I, those aspects of meibomian anatomy and physiology that are relevant to currently available tests are described; a fuller account of the anatomy and physiology is provided in the report of the Anatomy Subcommittee of this workshop. In part II, each test and its performance is described in detail. In part III, the practical application of selected tests is summarized and recommendations for future approaches are made. Additional recommendations and a summary of pertinent literature and concepts are presented in Appendices 1 to 17.

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.

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.

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 Schirmers 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.

TFOS DEWS II Diagnostic Methodology report

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

The TFOS International Workshop on Contact Lens Discomfort: Report of the contact lens interactions with the ocular surface and adnexa subcommittee

Efron, N., Jones, L., Bron, A. J., Knop, E., Arita, R., Barabino, S., … Markoulli, M. (2013). The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Interactions With the Ocular Surface and Adnexa Subcommittee. Investigative Opthalmology & Visual Science, 54(11), TFOS98. https://doi.org/10.1167/iovs.13-13187

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

PurposeTo 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).MethodsTwenty-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.ResultsOcular 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.ConclusionsAlthough 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.

Topical diquafosol for patients with obstructive meibomian gland dysfunction

Aims To evaluate the effect of topical diquafosol in patients with meibomian gland dysfunction (MGD) using tear film parameters and quantitatively analyse the meibomian gland morphology. Subjects and Methods The subjects were 19 eyes of 10 patients diagnosed with obstructive MGD. All subjects were given 3% diquafosol ophthalmic solution with instructions to use one drop four times a day. Ocular symptoms were scored from 0 to 14. Lid margin abnormalities were scored from 0 to 4. Changes in the meibomian glands were scored using non-contact meibography (meiboscore). Superficial punctate keratopathy (SPK) was scored from 0 to 3. Meibum was graded from 0 to 3. Tear film production was evaluated by Schirmers test. Quantitative image analysis of the meibomian glands was performed using the original software. Results 10 patients completed more than 4 months of therapy. Ocular symptoms, lid margin abnormalities, SPK score and meibum grade were decreased. Break-up time and tear film meniscus were increased. Mean ratio of the meibomian gland area was significantly increased after treatment (p<0.0001). Conclusions Quantitative image analysis was useful for evaluating the morphological changes of the meibomian glands. Topical diquafosol therapy was effective for patients with obstructive MGD.

Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss: A Multicenter Cross-sectional Study

PURPOSE To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. DESIGN Multicenter, cross-sectional, observational case series. PARTICIPANTS Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). METHODS Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmers test. MAIN OUTCOME MEASURES Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmers test value. RESULTS The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmers test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmers test value only in the MGD group (ρ = 0.508, P = 8.3×10(-6)). CONCLUSIONS An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

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 &bgr;-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.