- Email: [email protected]
Proposed Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction
Proposed Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction Reiko Arita, MD, PhD,1,2 Kouzo Itoh, MD, PhD,1 Syuji Maeda, MD, PhD,3 Koshi Maeda, MD, PhD,3 Ayumu Furuta, MD,3 Shima Fukuoka, MD,2 Atsuo Tomidokoro, MD, PhD,2 Shiro Amano, MD, PhD2 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. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2009;116:2058 –2063 © 2009 by the American Academy of Ophthalmology.
The meibomian glands secrete a lipid substance that protects the ocular surface by reducing water evaporation.1 Obstructive meibomian gland dysfunction (MGD) is characterized by the condensation of meibomian lipids, which results in the hyposecretion of lipids in tears.2 Obstructive MGD is a major cause of lipid layer deficiency and evaporative dry eye,3– 6 and often results in unstable tear film, damage to the ocular surface epithelium, chronic blepharitis, contact lens intolerance, and giant papillary conjunctivitis.7–12 Obstructive MGD is currently diagnosed by slitlamp examination of the lid margins and ocular surface epithelium,13 meibometry,14,15 assessment of the volume and properties of the meibum,5,16 meibography,17–21 assessment of tear interference,22,23 and assessment of the tear evaporation rate.24,25 To date, however, comprehensive diagnostic criteria for obstructive MGD have not been established. In meibography, the silhouette of the meibomian gland structure is observed by retroillumination of the everted eyelids from the skin side to obtain information on the
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© 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
morphologic characteristics of the meibomian glands. Although this technique was developed ⬎30 years ago, it is not widely used, probably because of the necessity of examiner expertise as well as patient discomfort during the examination, such as glare, heat, and pain induced by direct application of the probe to the eyelid. To address these problems, we developed a noncontact, patient-friendly meibography method that uses an infrared filter and an infrared charge-coupled device video camera.26 This meibography system allows for easy observation of the meibomian gland structures in both the upper and lower eyelids without inducing patient discomfort. Using this meibography system, we found that changes in meibomian glands increase with age and that contact lens wear is associated with a decrease in the number of functional meibomian glands.26,27 Because the noncontact meibography system provides detailed information regarding the status of obstruction of the entire meibomian gland structure, it is likely to facilitate the diagnosis of obstructive MGD. ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.04.037
Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction In the present study, we compared the results of various meibomian gland examination techniques, including the noncontact meibography system, between patients with obstructive MGD and normal controls. Based on our results, we propose diagnostic criteria for obstructive MGD.
Subjects and Methods Subjects The subjects were 53 right eyes of 53 patients (18 men, 35 women; age [mean ⫾ standard deviation] 71.4⫾10.0 years) who were diagnosed with obstructive MGD by an experienced ophthalmologist based on ocular symptoms, ⱖ1 lid margin abnormality (irregular lid margin, vascular engorgement, plugged meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction), and poor meibum expression. As a control group, 60 right eyes of 60 healthy volunteers (22 men, 38 women; age 71.0⫾9.3 years) were recruited. Exclusion criteria for both groups included ocular allergies, contact lens wear, continuous eye drop use, history of eye surgery, and systemic or ocular diseases that might interfere with tear film production or function. Patients whose eyes had excessive meibomian lipid secretion were also excluded. Written informed consent was obtained from all subjects before examination. This study was approved by the institutional review board of the Itoh clinic and adhered to the tenets of the Declaration of Helsinki.
Examinations Examinations were performed sequentially as follows. All patients and controls were questioned regarding the presence of 14 ocular symptoms: ocular fatigue, discharge, foreign body sensation, dryness, uncomfortable sensation, sticky sensation, pain, epiphora, itching, redness, heavy sensation, glare, excessive blinking, and history of chalazion or hordeolum. Symptoms were scored from 0 through 14 according to the number of these symptoms that were present. Four lid margin abnormalities (irregular lid margin, vascular engorgement, plugged meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities present in each eye. Superficial punctuate keratopathy (SPK) in the cornea was scored from 0 to 3. The tear film breakup time (BUT) was measured 3 times consecutively after the instillation of fluorescein and the median value was adopted. Using the noncontact meibography system, the upper and lower eyelids were everted and the meibomian glands were observed. Partial or complete loss of the meibomian glands was scored using the following grades (meibo-score) for each eyelid as previously described: 0, no loss of meibomian glands; 1, lost area was less than one third of the total area of meibomian glands; 2, lost area was between one third and two thirds of the total area of meibomian glands; and 3, lost area was over two thirds of the total area of meibomian glands.26 Meibo-scores for the upper and lower eyelids were summed to obtain a score from 0 through 6 for each eye. Tear film production was evaluated by the Schirmer test without application of topical anesthetics. Digital pressure was applied to the upper tarsus, and the degree of ease with which meibomian secretion (meibum) was induced was evaluated semiquantitatively as follows16: 0, clear meibum easily expressed; 1, cloudy meibum expressed with mild pressure; 2, cloudy meibum expressed with more than moderate pressure; and 3, meibum not expressed, even with hard pressure.
Statistical Analysis The frequency of each ocular symptom was compared between the obstructive MGD group and the control group using the chi-square method. The averages of the parameters were compared between the obstructive MGD group and the control group using the Mann– Whitney U test. The correlations among the parameters in the obstructive MGD group were calculated using Spearman’s correlation analysis. Receiver operating characteristic (ROC) curves with calculations of area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate obstructive MGD from normal subjects. P⬍0.05 was considered significant. Because a Spearman correlation analysis was performed 21 times, P⬍0.0023 was considered significant after the Bonferroni correction.
Results The obstructive MGD group had a significantly higher frequency of all 14 ocular symptoms than the control group (Table 1). The obstructive MGD group had a significantly higher average ocular symptom score than the control group (Table 2). The obstructive MGD group had a significantly higher mean lid margin abnormality score, SPK score, and meibum score than the control group (Table 2). The obstructive MGD group had a significantly shorter BUT than the control group (Table 2). The obstructive MGD group had a significantly higher average meibo-score than the control group (Table 2). Figure 1 shows representative results of meibography in the obstructive MGD group and the control group. Various meibomian gland changes, such as dropout, shortening, distortion, and gland dilation existed in all of the patients in the obstructive MGD group. The average Schirmer value did not significantly differ between the obstructive MGD group and the control group (Table 2). Correlation factors and significance levels among parameters in the obstructive MGD group are shown in Table 3. The meibo-score and the lid margin abnormality score were significantly correlated with the meibum score. The ROC curves and the AUC values are shown in Figure 2 and Table 2, respectively. 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. Table 1. Number of Subjects in the Obstructive Meibomian Gland Dysfunction (MGD; N ⫽ 53) and Control (N ⫽ 60) Groups Answering Affirmatively for Each Symptom on the Questionnaire Symptom
Obstructive MGD
Control
P
Ocular fatigue Discharge Foreign body sensation Dryness Uncomfortable sensation Sticky sensation Pain Epiphora Itching Redness Heavy sensation Glare Excessive blinking History of chalazion or hordeolum
34 15 47 33 31 12 14 16 16 20 16 13 7 8
16 3 2 9 9 1 0 4 1 2 6 5 0 1
⬍0.0001 0.0014 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.0005 ⬍0.0001 0.0012 ⬍0.0001 ⬍0.0001 0.0087 0.0222 0.0040 0.0121
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Ophthalmology Volume 116, Number 11, November 2009 Table 2. Mean Value (⫾ Standard Deviation) of Parameters and Areas Under the Receiver Operating Characteristics Curves (AUC) with 95% Confidence Intervals (CI) Parameters
MGD (n ⴝ 53)
Normal (n ⴝ 60)
P-Value
AUC
95% CI
Symptoms Lid abnormality Meibo-score Meibum SPK BUT Schirmer
5.28⫾2.74 2.62⫾1.08 4.23⫾1.60 1.87⫾1.00 0.64⫾0.79 3.08⫾2.04 12.3⫾7.5
0.88⫾1.17 0.55⫾0.70 1.55⫾0.85 0.72⫾0.72 0⫾0 6.40⫾2.04 10.3⫾5.3
⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.173
0.948 0.933 0.918 0.802 0.736 0.862 0.574
0.912–0.984 0.891–0.974 0.866–0.970 0.722–0.883 0.640–0.832 0.793–0.932 0.467–0.681
BUT ⫽ tear film breakup time; MGD ⫽ meibomian gland dysfunction; SPK ⫽ superficial punctate keratopathy.
A Venn diagram analysis was performed to gain insight into how the 3 scores with the highest AUC (ocular symptom score, lid margin abnormality score, and meibo-score) contribute to the diagnosis of obstructive MGD (Fig 3). The cutoff value for each score was determined as the score whose corresponding point on the ROC curve was nearest to the coordinate (0, 1) on the graph of the ROC curves. An ocular symptom score of ⱖ3, a lid margin score of ⱖ2, and a meibo-score of ⱖ3 was considered abnormal. When a true positive was detected by a single score, it was most often a symptom score (5 cases). On the other hand, the 3 scores were similarly prone to produce a false-positive result (7 cases in symptom score, 5 cases in lid margin abnormality score, and 5 cases in meibo-score). When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores being abnormal, the sensitivity was 100% and the specificity was 68.3%. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, the sensitivity was 84.9% and the specificity was 96.7%. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the sensitivity was 66.0% and the specificity was 100%.
Discussion Patients with obstructive MGD and control subjects differed significantly on all parameters examined in this study, except the Schirmer test. Because the patients in the obstructive MGD group were recruited based on the presence of ocular symptoms, lid margin abnormalities, and poor meibum expression, it is reasonable that the parameters differed significantly between the 2 groups. The meibo-score, SPK score, and BUT also differed significantly between the 2 groups. These results suggest that these parameters, that is, ocular symptom score, lid margin abnormality score, meibum score, meibo-score, SPK score, and BUT, can be used to differentiate patients with obstructive MGD from normal subjects. The frequency of all 14 symptoms was significantly higher in the obstructive MGD group than in the control group. Moreover, ROC analysis indicated that the symptom score had the highest power to differentiate patients with
Figure 1. Representative results of meibography in the obstructive meibomian gland dysfunction (MGD) group (A, B) and the control group (C, D). A, B, A 67-year-old woman in the obstructive MGD group. Gland dropout (area encircled with dotted white lines), shortening (arrows), and distortion (arrowhead) were recognized. The meibo-score was 1 in both upper and lower eyelids, and the total meibo-score was 2. C, D, A 64-year-old woman in the control group. Meibomian gland changes were not observed. Meibo-score was 0 in both upper and lower eyelids, and the total meibo-score was 0.
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Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction Table 3. Correlation Factors and P Values among Variables in the Obstructive Meibomian Gland Dysfunction Group
Symptoms Lid Meibum SPK BUT Meibo-score Schirmer
Symptoms
Lid Score
Meibum
SPK
BUT
Meibo-score
⫺0.07 P ⫽ 0.60 ⫺0.12 P ⫽ 0.40 0.33 P ⫽ 0.02 ⫺0.081 P ⫽ 0.56 ⫺0.23 P ⫽ 0.09 0.12 P ⫽ 0.41
0.50 P ⫽ 0.0003 0.038 P ⫽ 0.79 0.14 P ⫽ 0.32 0.32 P ⫽ 0.02 ⫺0.19 P ⫽ 0.18
0.28 P ⫽ 0.046 0.082 P ⫽ 0.56 0.53 P⬍0.0001 ⫺0.27 P ⫽ 0.06
⫺0.027 P ⫽ 0.85 0.15 P ⫽ 0.29 ⫺0.08 P ⫽ 0.58
0.25 P ⫽ 0.08 ⫺0.04 P ⫽ 0.76
⫺0.14 P ⫽ 0.30
Correlation factors with significance levels after Bonferroni’s correction are indicated in bold. BUT ⫽ tear film breakup time; SPK ⫽ superficial punctate keratopathy.
MGD from normal subjects. These findings indicate that the questionnaire (Appendix 1, available online at http:// aaojournal.org) used in the present study is a potentially useful tool for diagnosing obstructive MGD. However, the current questionnaire seems to need some refinements. First, several symptoms in the questionnaire seem to have overlapping meaning. A same patient is likely to have ocular fatigue, uncomfortable sensation, and heavy sensation. Likewise, a patient with discharge will most likely have itching and sticky sensation causing a score of 3. Although it may be difficult to create a questionnaire with an entirely independent symptoms owing to subjective symptoms’ vague boundaries of meaning, refinement of questions with less overlapping meanings is needed. Second, nonspecific
Figure 2. Receiver operating characteristic curves for the seven parameters related to meibomian gland dysfunction.
symptoms in the questionnaire can be induced by diseases other than MGD, such as aqueous deficiency, endocrinal changes, lid laxity, and lacrimal drainage problems. Because the 14 symptoms addressed in the questionnaire were selected based on questionnaires used for dry eye syndrome,28 the questionnaire is not likely to have a high power for differentiating patients with obstructive MGD from patients with dry eye syndrome caused by other mechanisms such as aqueous deficiency. More refined questionnaire that are specific to obstructive MGD should be developed in future studies. Third, because many elderly persons are likely to have MGD without significant symptoms, the questionnaire alone may not be enough to diagnose MGD. As shown in the results, however, the diagnostic power can be improved by combining the questionnaire with lid margin abnormality score and meibo-score. The lid margin abnormality was scored based on the presence of 4 lid margin findings that are frequently observed in patients with MGD. The lid margin abnormality score was significantly higher in the obstructive MGD group than in the control group, consistent with a previous study.13 The AUC of the lid margin abnormality score in the ROC analysis was the second highest symptom score, indicating that the lid margin abnormality score has a high power to differentiate MGD from the normal population. When the diagnosis for obstructive MGD was made based on a lid margin abnormality score of ⱖ2, the sensitivity was 81.1% and the specificity was 88.3%, which is nearest to the coordinate (0, 1) in the graph of the ROC curves. The meibo-score was significantly higher for obstructive MGD patients than for controls. The ROC analysis indicated that the AUC of the meibo-score was similar to those of the symptom and lid margin abnormality scores, indicating that the meibo-score has a similarly high power to differentiate MGD from the normal population. Moreover, the meibo-score significantly and positively correlated with the lid margin abnormality and meibum scores, suggesting that the meibo-score correlates with meibomian gland function.
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Figure 3. A Venn diagram analysis of 53 eyes with meibomian gland dysfunction (MGD; A) and 60 control eyes (B). When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores (ocular symptom score, lid margin abnormality score, and meibo-score) being abnormal, the sensitivity was 100% and the specificity was 68.3%. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, the sensitivity was 84.9% and the specificity was 96.7%. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the sensitivity was 66.0% and the specificity was 100%.
In our previous study using the same meibography technique, we demonstrated that meibomian gland changes in a normal population increase with age.26 Focal gland dropout was a typical meibomian gland change that occurred with aging. However, among patients with obstructive MGD, various meibomian gland changes were observed, including gland dropout, shortening, distortion, dilation, cut off
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in the middle, and hairpin-loop-like changes; most of these changes began at the orifice side. These differences in the pattern of meibomian gland changes might contribute to differentiate MGD from age-related changes in meibomian glands. Because MGD is characterized by a stagnation of meibomian secretion, the meibum score is expected to have a high power to differentiate patients with obstructive MGD from normal subjects. However, in the present study the power of the meibum score was lower than that of the symptom score, lid margin abnormality score, and meiboscore. There are several possible reasons for the lower power of the meibum score. First, the objectivity and reproducibility of meibum scoring are low because the expression pressure on the eyelid is not easily defined. Second, meibum score is determined by the meibum expressibility solely from pressure at the center of eyelids, although meibomian gland changes in obstructive MGD are diffuse. However, meibo-score, lid margin abnormality score, and symptom score are thought to reflect the whole area of the eyelid, which is likely to contribute to the higher power of these scores to differentiate patients with obstructive MGD from normal subjects. When a more objective and reproducible method to score meibum is developed, the meibum score is likely to have a higher power to differentiate patients with obstructive MGD from normal subjects. The SPK score was higher in patients with obstructive MGD than in the controls; the BUT was also shorter in patients with obstructive MGD than in the controls. These findings are consistent those in previous reports.5,29,30 Both SPK score and BUT, however, had relatively lower power to differentiate MGD from normal subjects. Moreover, because patients with dry eye syndrome are likely to have a higher SPK score and a lower BUT than normal subjects, these scores are likely to have even lower power to differentiate MGD from dry eye syndrome owing to aqueous deficiency. There was no significant difference in the Schirmer values between the obstructive MGD and control groups. This result seems reasonable because the Schirmer test measures the aqueous volume of tear film, which is not related to meibomian gland function. Although this result suggests that most cases in the MGD group did not have aqueous deficiency, several patients with a low Schirmer value were included in the study. If the exclusion criteria should have included a low Schirmer value, this would have made the MGD group more specific for having a single cause for poor tear film instead of a highly possible confounding cause (aqueous deficiency). A limitation of this study is that the diagnostic criteria were based on 1 set of MGD patients and normal subjects and the efficacy of the criteria was not confirmed in another set of MGD patients and normal subjects. The efficacy of the diagnostic criteria proposed in this study should be confirmed in future studies. The findings of the present study suggest that symptom score, lid margin abnormality score, and meibo-score are the best candidate diagnostic criteria for obstructive MGD. Thus, we used Venn diagrams to gain insight into how these 3 scores contribute to the diagnosis of obstructive MGD.
Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores being abnormal, the sensitivity was 100%, but the specificity was relatively low. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, both the sensitivity and specificity were high. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the specificity was 100% but the sensitivity was relatively low. Based on these results, we recommend that physicians use symptom score, lid margin abnormality score, and meiboscore for the diagnosis of 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.
References 1. Mishima S, Maurice DM. The oily layer of the tear film and evaporation from the corneal surface. Exp Eye Res 1961;1: 39 – 45. 2. McCulley JP. Meibomitis. In: Kaufman HE, Barron BA, McDonald MB, Waltman SR, eds. The Cornea. New York: Churchill Livingstone; 1988:125–38. 3. Lemp MA. Report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21: 221–32. 4. Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 1993;100:347–51. 5. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch Ophthalmol 1995;113:1266 –70. 6. Lee SH, Tseng SC. Rose Bengal staining and cytologic characteristics associated with lipid tear deficiency. Am J Ophthalmol 1997;124:736 –50. 7. Mathers WD, Shields WJ, Sachdev MS, et al. Meibomian gland dysfunction in chronic blepharitis. Cornea 1991;10: 277– 85. 8. Mathers WD, Billborough M. Meibomian gland function and giant papillary conjunctivitis. Am J Ophthalmol 1992;114: 188 –92. 9. Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc 1980;51:243–51. 10. Henriquez AS, Korb DR. Meibomian glands and contact lens wear. Br J Ophthalmol 1981;65:108 –11. 11. Zengin N, Tol H, Gunduz K, et al. Meibomian gland dysfunction and tear film abnormalities in rosacea. Cornea 1995;14: 144 – 6. 12. Ong BL. Relation between contact lens wear and Meibomian gland dysfunction. Optom Vis Sci 1996;73:208 –10.
13. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease: classification and grading of lid changes. Eye 1991;5:395– 411. 14. Yokoi N, Mossa F, Tiffany JM, Bron AJ. Assessment of meibomian gland function in dry eye using meibometry. Arch Ophthalmol 1999;117:723–9. 15. Chew CK, Jansweijer C, Tiffany JM, et al. An instrument for quantifying meibomian lipid on the lid margin: the meibometer. Curr Eye Res 1993;12:247–54. 16. Shimazaki J, Goto E, Ono M, et al. Meibomian gland dysfunction in patients with Sjögren syndrome. Ophthalmology 1998;105:1485– 8. 17. Tapie R. Biomicroscopial study of Meibomian glands [in French]. Ann Ocul (Paris) 1977;210:637– 48. 18. Robin JB, Jester JV, Nobe J, et al. In vivo transillumination biomicroscopy and photography of meibomian gland dysfunction: a clinical study. Ophthalmology 1985;92: 1423– 6. 19. Mathers WD, Daley T, Verdick R. Video imaging of the meibomian gland [letter]. Arch Ophthalmol 1994;112:448 –9. 20. Yokoi N, Komuro A, Yamada H, et al. A newly developed video-meibography system featuring a newly designed probe. Jpn J Ophthalmol 2007;51:53– 6. 21. Nichols JJ, Berntsen DA, Mitchell GL, Nichols KK. An assessment of grading scales for meibography images. Cornea 2005;24:382– 8. 22. Korb DR, Greiner JV. Increase in tear film lipid layer thickness following treatment of meibomian gland dysfunction. Adv Exp Med Biol 1994;350:293– 8. 23. Korb DR, Baron DF, Herman JP, et al. Tear film lipid layer thickness as a function of blinking. Cornea 1994;13:354 –9. 24. Mathers WD, Binarao G, Petroll M. Ocular water evaporation and the dry eye: a new measuring device. Cornea 1993;12: 335– 40. 25. Goto E, Endo K, Suzuki A, et al. Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2003;44:533–9. 26. Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008; 115:911–5. 27. Arita R, Itoh K, Inoue K, et al. Contact lens wear is associated with decrease of meibomian glands. Ophthalmology 2009; 116:379 – 84. 28. Toda I, Fujishima H, Tsubota K. Ocular fatigue is the major symptom of dry eye. Acta Ophthalmol (Copehn) 1993;71: 347–52. 29. McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Ophthalmol 1977;84:788 –93. 30. Pflugfelder SC, Tseng CG, Sanabria O, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea 1998;17:38 –56.
Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: February 25, 2009. Accepted: April 11, 2009. Available online: September 10, 2009. 1
Drs Arita and Amano are applying with Topcon for a patent in the meibography technique described in this manuscript. Manuscript no. 2009-51.
Itoh Clinic, Saitama, Japan.
2
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan. 3
Maeda Ophthalmic Clinic, Fukushima, Japan.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Reiko Arita, MD, PhD, 626-11 Minaminakano, Minuma-ku, Saitama city, Saitama, 337-0042, Japan. E-mail: [email protected].
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Appendix 1. Exact English Translation of the Questionnaire 1. 2. 3. 4. 5.
Do Do Do Do Do
2063.e1
you you you you you
have have have have have
ocular fatigue? uncomfortable sensation in your eye? heavy sensation in your eye? discharge? itching sensation in your eye?
6. 7. 8. 9. 10. 11. 12. 13. 14.
Do Do Do Do Do Do Do Do Do
you you you you you you you you you
have have have have have have have have have
sticky sensation in your eye? glare? excessive blinking? dryness in your eye? pain in your eye? foreign body sensation in your eye? epiphora? redness in your eye? a history of chalazion or hordeolum?
The meibomian glands secrete a lipid substance that protects the ocular surface by reducing water evaporation.1 Obstructive meibomian gland dysfunction (MGD) is characterized by the condensation of meibomian lipids, which results in the hyposecretion of lipids in tears.2 Obstructive MGD is a major cause of lipid layer deficiency and evaporative dry eye,3– 6 and often results in unstable tear film, damage to the ocular surface epithelium, chronic blepharitis, contact lens intolerance, and giant papillary conjunctivitis.7–12 Obstructive MGD is currently diagnosed by slitlamp examination of the lid margins and ocular surface epithelium,13 meibometry,14,15 assessment of the volume and properties of the meibum,5,16 meibography,17–21 assessment of tear interference,22,23 and assessment of the tear evaporation rate.24,25 To date, however, comprehensive diagnostic criteria for obstructive MGD have not been established. In meibography, the silhouette of the meibomian gland structure is observed by retroillumination of the everted eyelids from the skin side to obtain information on the
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© 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
morphologic characteristics of the meibomian glands. Although this technique was developed ⬎30 years ago, it is not widely used, probably because of the necessity of examiner expertise as well as patient discomfort during the examination, such as glare, heat, and pain induced by direct application of the probe to the eyelid. To address these problems, we developed a noncontact, patient-friendly meibography method that uses an infrared filter and an infrared charge-coupled device video camera.26 This meibography system allows for easy observation of the meibomian gland structures in both the upper and lower eyelids without inducing patient discomfort. Using this meibography system, we found that changes in meibomian glands increase with age and that contact lens wear is associated with a decrease in the number of functional meibomian glands.26,27 Because the noncontact meibography system provides detailed information regarding the status of obstruction of the entire meibomian gland structure, it is likely to facilitate the diagnosis of obstructive MGD. ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.04.037
Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction In the present study, we compared the results of various meibomian gland examination techniques, including the noncontact meibography system, between patients with obstructive MGD and normal controls. Based on our results, we propose diagnostic criteria for obstructive MGD.
Subjects and Methods Subjects The subjects were 53 right eyes of 53 patients (18 men, 35 women; age [mean ⫾ standard deviation] 71.4⫾10.0 years) who were diagnosed with obstructive MGD by an experienced ophthalmologist based on ocular symptoms, ⱖ1 lid margin abnormality (irregular lid margin, vascular engorgement, plugged meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction), and poor meibum expression. As a control group, 60 right eyes of 60 healthy volunteers (22 men, 38 women; age 71.0⫾9.3 years) were recruited. Exclusion criteria for both groups included ocular allergies, contact lens wear, continuous eye drop use, history of eye surgery, and systemic or ocular diseases that might interfere with tear film production or function. Patients whose eyes had excessive meibomian lipid secretion were also excluded. Written informed consent was obtained from all subjects before examination. This study was approved by the institutional review board of the Itoh clinic and adhered to the tenets of the Declaration of Helsinki.
Examinations Examinations were performed sequentially as follows. All patients and controls were questioned regarding the presence of 14 ocular symptoms: ocular fatigue, discharge, foreign body sensation, dryness, uncomfortable sensation, sticky sensation, pain, epiphora, itching, redness, heavy sensation, glare, excessive blinking, and history of chalazion or hordeolum. Symptoms were scored from 0 through 14 according to the number of these symptoms that were present. Four lid margin abnormalities (irregular lid margin, vascular engorgement, plugged meibomian gland orifices, and anterior or posterior replacement of the mucocutaneous junction) were scored from 0 through 4 according to the number of these abnormalities present in each eye. Superficial punctuate keratopathy (SPK) in the cornea was scored from 0 to 3. The tear film breakup time (BUT) was measured 3 times consecutively after the instillation of fluorescein and the median value was adopted. Using the noncontact meibography system, the upper and lower eyelids were everted and the meibomian glands were observed. Partial or complete loss of the meibomian glands was scored using the following grades (meibo-score) for each eyelid as previously described: 0, no loss of meibomian glands; 1, lost area was less than one third of the total area of meibomian glands; 2, lost area was between one third and two thirds of the total area of meibomian glands; and 3, lost area was over two thirds of the total area of meibomian glands.26 Meibo-scores for the upper and lower eyelids were summed to obtain a score from 0 through 6 for each eye. Tear film production was evaluated by the Schirmer test without application of topical anesthetics. Digital pressure was applied to the upper tarsus, and the degree of ease with which meibomian secretion (meibum) was induced was evaluated semiquantitatively as follows16: 0, clear meibum easily expressed; 1, cloudy meibum expressed with mild pressure; 2, cloudy meibum expressed with more than moderate pressure; and 3, meibum not expressed, even with hard pressure.
Statistical Analysis The frequency of each ocular symptom was compared between the obstructive MGD group and the control group using the chi-square method. The averages of the parameters were compared between the obstructive MGD group and the control group using the Mann– Whitney U test. The correlations among the parameters in the obstructive MGD group were calculated using Spearman’s correlation analysis. Receiver operating characteristic (ROC) curves with calculations of area under the curve (AUC) were used to describe the accuracy of each parameter to differentiate obstructive MGD from normal subjects. P⬍0.05 was considered significant. Because a Spearman correlation analysis was performed 21 times, P⬍0.0023 was considered significant after the Bonferroni correction.
Results The obstructive MGD group had a significantly higher frequency of all 14 ocular symptoms than the control group (Table 1). The obstructive MGD group had a significantly higher average ocular symptom score than the control group (Table 2). The obstructive MGD group had a significantly higher mean lid margin abnormality score, SPK score, and meibum score than the control group (Table 2). The obstructive MGD group had a significantly shorter BUT than the control group (Table 2). The obstructive MGD group had a significantly higher average meibo-score than the control group (Table 2). Figure 1 shows representative results of meibography in the obstructive MGD group and the control group. Various meibomian gland changes, such as dropout, shortening, distortion, and gland dilation existed in all of the patients in the obstructive MGD group. The average Schirmer value did not significantly differ between the obstructive MGD group and the control group (Table 2). Correlation factors and significance levels among parameters in the obstructive MGD group are shown in Table 3. The meibo-score and the lid margin abnormality score were significantly correlated with the meibum score. The ROC curves and the AUC values are shown in Figure 2 and Table 2, respectively. 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. Table 1. Number of Subjects in the Obstructive Meibomian Gland Dysfunction (MGD; N ⫽ 53) and Control (N ⫽ 60) Groups Answering Affirmatively for Each Symptom on the Questionnaire Symptom
Obstructive MGD
Control
P
Ocular fatigue Discharge Foreign body sensation Dryness Uncomfortable sensation Sticky sensation Pain Epiphora Itching Redness Heavy sensation Glare Excessive blinking History of chalazion or hordeolum
34 15 47 33 31 12 14 16 16 20 16 13 7 8
16 3 2 9 9 1 0 4 1 2 6 5 0 1
⬍0.0001 0.0014 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.0005 ⬍0.0001 0.0012 ⬍0.0001 ⬍0.0001 0.0087 0.0222 0.0040 0.0121
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Ophthalmology Volume 116, Number 11, November 2009 Table 2. Mean Value (⫾ Standard Deviation) of Parameters and Areas Under the Receiver Operating Characteristics Curves (AUC) with 95% Confidence Intervals (CI) Parameters
MGD (n ⴝ 53)
Normal (n ⴝ 60)
P-Value
AUC
95% CI
Symptoms Lid abnormality Meibo-score Meibum SPK BUT Schirmer
5.28⫾2.74 2.62⫾1.08 4.23⫾1.60 1.87⫾1.00 0.64⫾0.79 3.08⫾2.04 12.3⫾7.5
0.88⫾1.17 0.55⫾0.70 1.55⫾0.85 0.72⫾0.72 0⫾0 6.40⫾2.04 10.3⫾5.3
⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 0.173
0.948 0.933 0.918 0.802 0.736 0.862 0.574
0.912–0.984 0.891–0.974 0.866–0.970 0.722–0.883 0.640–0.832 0.793–0.932 0.467–0.681
BUT ⫽ tear film breakup time; MGD ⫽ meibomian gland dysfunction; SPK ⫽ superficial punctate keratopathy.
A Venn diagram analysis was performed to gain insight into how the 3 scores with the highest AUC (ocular symptom score, lid margin abnormality score, and meibo-score) contribute to the diagnosis of obstructive MGD (Fig 3). The cutoff value for each score was determined as the score whose corresponding point on the ROC curve was nearest to the coordinate (0, 1) on the graph of the ROC curves. An ocular symptom score of ⱖ3, a lid margin score of ⱖ2, and a meibo-score of ⱖ3 was considered abnormal. When a true positive was detected by a single score, it was most often a symptom score (5 cases). On the other hand, the 3 scores were similarly prone to produce a false-positive result (7 cases in symptom score, 5 cases in lid margin abnormality score, and 5 cases in meibo-score). When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores being abnormal, the sensitivity was 100% and the specificity was 68.3%. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, the sensitivity was 84.9% and the specificity was 96.7%. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the sensitivity was 66.0% and the specificity was 100%.
Discussion Patients with obstructive MGD and control subjects differed significantly on all parameters examined in this study, except the Schirmer test. Because the patients in the obstructive MGD group were recruited based on the presence of ocular symptoms, lid margin abnormalities, and poor meibum expression, it is reasonable that the parameters differed significantly between the 2 groups. The meibo-score, SPK score, and BUT also differed significantly between the 2 groups. These results suggest that these parameters, that is, ocular symptom score, lid margin abnormality score, meibum score, meibo-score, SPK score, and BUT, can be used to differentiate patients with obstructive MGD from normal subjects. The frequency of all 14 symptoms was significantly higher in the obstructive MGD group than in the control group. Moreover, ROC analysis indicated that the symptom score had the highest power to differentiate patients with
Figure 1. Representative results of meibography in the obstructive meibomian gland dysfunction (MGD) group (A, B) and the control group (C, D). A, B, A 67-year-old woman in the obstructive MGD group. Gland dropout (area encircled with dotted white lines), shortening (arrows), and distortion (arrowhead) were recognized. The meibo-score was 1 in both upper and lower eyelids, and the total meibo-score was 2. C, D, A 64-year-old woman in the control group. Meibomian gland changes were not observed. Meibo-score was 0 in both upper and lower eyelids, and the total meibo-score was 0.
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Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction Table 3. Correlation Factors and P Values among Variables in the Obstructive Meibomian Gland Dysfunction Group
Symptoms Lid Meibum SPK BUT Meibo-score Schirmer
Symptoms
Lid Score
Meibum
SPK
BUT
Meibo-score
⫺0.07 P ⫽ 0.60 ⫺0.12 P ⫽ 0.40 0.33 P ⫽ 0.02 ⫺0.081 P ⫽ 0.56 ⫺0.23 P ⫽ 0.09 0.12 P ⫽ 0.41
0.50 P ⫽ 0.0003 0.038 P ⫽ 0.79 0.14 P ⫽ 0.32 0.32 P ⫽ 0.02 ⫺0.19 P ⫽ 0.18
0.28 P ⫽ 0.046 0.082 P ⫽ 0.56 0.53 P⬍0.0001 ⫺0.27 P ⫽ 0.06
⫺0.027 P ⫽ 0.85 0.15 P ⫽ 0.29 ⫺0.08 P ⫽ 0.58
0.25 P ⫽ 0.08 ⫺0.04 P ⫽ 0.76
⫺0.14 P ⫽ 0.30
Correlation factors with significance levels after Bonferroni’s correction are indicated in bold. BUT ⫽ tear film breakup time; SPK ⫽ superficial punctate keratopathy.
MGD from normal subjects. These findings indicate that the questionnaire (Appendix 1, available online at http:// aaojournal.org) used in the present study is a potentially useful tool for diagnosing obstructive MGD. However, the current questionnaire seems to need some refinements. First, several symptoms in the questionnaire seem to have overlapping meaning. A same patient is likely to have ocular fatigue, uncomfortable sensation, and heavy sensation. Likewise, a patient with discharge will most likely have itching and sticky sensation causing a score of 3. Although it may be difficult to create a questionnaire with an entirely independent symptoms owing to subjective symptoms’ vague boundaries of meaning, refinement of questions with less overlapping meanings is needed. Second, nonspecific
Figure 2. Receiver operating characteristic curves for the seven parameters related to meibomian gland dysfunction.
symptoms in the questionnaire can be induced by diseases other than MGD, such as aqueous deficiency, endocrinal changes, lid laxity, and lacrimal drainage problems. Because the 14 symptoms addressed in the questionnaire were selected based on questionnaires used for dry eye syndrome,28 the questionnaire is not likely to have a high power for differentiating patients with obstructive MGD from patients with dry eye syndrome caused by other mechanisms such as aqueous deficiency. More refined questionnaire that are specific to obstructive MGD should be developed in future studies. Third, because many elderly persons are likely to have MGD without significant symptoms, the questionnaire alone may not be enough to diagnose MGD. As shown in the results, however, the diagnostic power can be improved by combining the questionnaire with lid margin abnormality score and meibo-score. The lid margin abnormality was scored based on the presence of 4 lid margin findings that are frequently observed in patients with MGD. The lid margin abnormality score was significantly higher in the obstructive MGD group than in the control group, consistent with a previous study.13 The AUC of the lid margin abnormality score in the ROC analysis was the second highest symptom score, indicating that the lid margin abnormality score has a high power to differentiate MGD from the normal population. When the diagnosis for obstructive MGD was made based on a lid margin abnormality score of ⱖ2, the sensitivity was 81.1% and the specificity was 88.3%, which is nearest to the coordinate (0, 1) in the graph of the ROC curves. The meibo-score was significantly higher for obstructive MGD patients than for controls. The ROC analysis indicated that the AUC of the meibo-score was similar to those of the symptom and lid margin abnormality scores, indicating that the meibo-score has a similarly high power to differentiate MGD from the normal population. Moreover, the meibo-score significantly and positively correlated with the lid margin abnormality and meibum scores, suggesting that the meibo-score correlates with meibomian gland function.
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Figure 3. A Venn diagram analysis of 53 eyes with meibomian gland dysfunction (MGD; A) and 60 control eyes (B). When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores (ocular symptom score, lid margin abnormality score, and meibo-score) being abnormal, the sensitivity was 100% and the specificity was 68.3%. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, the sensitivity was 84.9% and the specificity was 96.7%. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the sensitivity was 66.0% and the specificity was 100%.
In our previous study using the same meibography technique, we demonstrated that meibomian gland changes in a normal population increase with age.26 Focal gland dropout was a typical meibomian gland change that occurred with aging. However, among patients with obstructive MGD, various meibomian gland changes were observed, including gland dropout, shortening, distortion, dilation, cut off
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in the middle, and hairpin-loop-like changes; most of these changes began at the orifice side. These differences in the pattern of meibomian gland changes might contribute to differentiate MGD from age-related changes in meibomian glands. Because MGD is characterized by a stagnation of meibomian secretion, the meibum score is expected to have a high power to differentiate patients with obstructive MGD from normal subjects. However, in the present study the power of the meibum score was lower than that of the symptom score, lid margin abnormality score, and meiboscore. There are several possible reasons for the lower power of the meibum score. First, the objectivity and reproducibility of meibum scoring are low because the expression pressure on the eyelid is not easily defined. Second, meibum score is determined by the meibum expressibility solely from pressure at the center of eyelids, although meibomian gland changes in obstructive MGD are diffuse. However, meibo-score, lid margin abnormality score, and symptom score are thought to reflect the whole area of the eyelid, which is likely to contribute to the higher power of these scores to differentiate patients with obstructive MGD from normal subjects. When a more objective and reproducible method to score meibum is developed, the meibum score is likely to have a higher power to differentiate patients with obstructive MGD from normal subjects. The SPK score was higher in patients with obstructive MGD than in the controls; the BUT was also shorter in patients with obstructive MGD than in the controls. These findings are consistent those in previous reports.5,29,30 Both SPK score and BUT, however, had relatively lower power to differentiate MGD from normal subjects. Moreover, because patients with dry eye syndrome are likely to have a higher SPK score and a lower BUT than normal subjects, these scores are likely to have even lower power to differentiate MGD from dry eye syndrome owing to aqueous deficiency. There was no significant difference in the Schirmer values between the obstructive MGD and control groups. This result seems reasonable because the Schirmer test measures the aqueous volume of tear film, which is not related to meibomian gland function. Although this result suggests that most cases in the MGD group did not have aqueous deficiency, several patients with a low Schirmer value were included in the study. If the exclusion criteria should have included a low Schirmer value, this would have made the MGD group more specific for having a single cause for poor tear film instead of a highly possible confounding cause (aqueous deficiency). A limitation of this study is that the diagnostic criteria were based on 1 set of MGD patients and normal subjects and the efficacy of the criteria was not confirmed in another set of MGD patients and normal subjects. The efficacy of the diagnostic criteria proposed in this study should be confirmed in future studies. The findings of the present study suggest that symptom score, lid margin abnormality score, and meibo-score are the best candidate diagnostic criteria for obstructive MGD. Thus, we used Venn diagrams to gain insight into how these 3 scores contribute to the diagnosis of obstructive MGD.
Arita et al 䡠 Diagnostic Criteria for Obstructive Meibomian Gland Dysfunction When the diagnosis for obstructive MGD was made based on any 1 of the 3 scores being abnormal, the sensitivity was 100%, but the specificity was relatively low. When the diagnosis for obstructive MGD was made based on any 2 of the 3 scores being abnormal, both the sensitivity and specificity were high. When the diagnosis for obstructive MGD was made based on all 3 scores being abnormal, the specificity was 100% but the sensitivity was relatively low. Based on these results, we recommend that physicians use symptom score, lid margin abnormality score, and meiboscore for the diagnosis of 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.
References 1. Mishima S, Maurice DM. The oily layer of the tear film and evaporation from the corneal surface. Exp Eye Res 1961;1: 39 – 45. 2. McCulley JP. Meibomitis. In: Kaufman HE, Barron BA, McDonald MB, Waltman SR, eds. The Cornea. New York: Churchill Livingstone; 1988:125–38. 3. Lemp MA. Report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21: 221–32. 4. Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 1993;100:347–51. 5. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch Ophthalmol 1995;113:1266 –70. 6. Lee SH, Tseng SC. Rose Bengal staining and cytologic characteristics associated with lipid tear deficiency. Am J Ophthalmol 1997;124:736 –50. 7. Mathers WD, Shields WJ, Sachdev MS, et al. Meibomian gland dysfunction in chronic blepharitis. Cornea 1991;10: 277– 85. 8. Mathers WD, Billborough M. Meibomian gland function and giant papillary conjunctivitis. Am J Ophthalmol 1992;114: 188 –92. 9. Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc 1980;51:243–51. 10. Henriquez AS, Korb DR. Meibomian glands and contact lens wear. Br J Ophthalmol 1981;65:108 –11. 11. Zengin N, Tol H, Gunduz K, et al. Meibomian gland dysfunction and tear film abnormalities in rosacea. Cornea 1995;14: 144 – 6. 12. Ong BL. Relation between contact lens wear and Meibomian gland dysfunction. Optom Vis Sci 1996;73:208 –10.
13. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease: classification and grading of lid changes. Eye 1991;5:395– 411. 14. Yokoi N, Mossa F, Tiffany JM, Bron AJ. Assessment of meibomian gland function in dry eye using meibometry. Arch Ophthalmol 1999;117:723–9. 15. Chew CK, Jansweijer C, Tiffany JM, et al. An instrument for quantifying meibomian lipid on the lid margin: the meibometer. Curr Eye Res 1993;12:247–54. 16. Shimazaki J, Goto E, Ono M, et al. Meibomian gland dysfunction in patients with Sjögren syndrome. Ophthalmology 1998;105:1485– 8. 17. Tapie R. Biomicroscopial study of Meibomian glands [in French]. Ann Ocul (Paris) 1977;210:637– 48. 18. Robin JB, Jester JV, Nobe J, et al. In vivo transillumination biomicroscopy and photography of meibomian gland dysfunction: a clinical study. Ophthalmology 1985;92: 1423– 6. 19. Mathers WD, Daley T, Verdick R. Video imaging of the meibomian gland [letter]. Arch Ophthalmol 1994;112:448 –9. 20. Yokoi N, Komuro A, Yamada H, et al. A newly developed video-meibography system featuring a newly designed probe. Jpn J Ophthalmol 2007;51:53– 6. 21. Nichols JJ, Berntsen DA, Mitchell GL, Nichols KK. An assessment of grading scales for meibography images. Cornea 2005;24:382– 8. 22. Korb DR, Greiner JV. Increase in tear film lipid layer thickness following treatment of meibomian gland dysfunction. Adv Exp Med Biol 1994;350:293– 8. 23. Korb DR, Baron DF, Herman JP, et al. Tear film lipid layer thickness as a function of blinking. Cornea 1994;13:354 –9. 24. Mathers WD, Binarao G, Petroll M. Ocular water evaporation and the dry eye: a new measuring device. Cornea 1993;12: 335– 40. 25. Goto E, Endo K, Suzuki A, et al. Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2003;44:533–9. 26. Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008; 115:911–5. 27. Arita R, Itoh K, Inoue K, et al. Contact lens wear is associated with decrease of meibomian glands. Ophthalmology 2009; 116:379 – 84. 28. Toda I, Fujishima H, Tsubota K. Ocular fatigue is the major symptom of dry eye. Acta Ophthalmol (Copehn) 1993;71: 347–52. 29. McCulley JP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Ophthalmol 1977;84:788 –93. 30. Pflugfelder SC, Tseng CG, Sanabria O, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea 1998;17:38 –56.
Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: February 25, 2009. Accepted: April 11, 2009. Available online: September 10, 2009. 1
Drs Arita and Amano are applying with Topcon for a patent in the meibography technique described in this manuscript. Manuscript no. 2009-51.
Itoh Clinic, Saitama, Japan.
2
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan. 3
Maeda Ophthalmic Clinic, Fukushima, Japan.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: Reiko Arita, MD, PhD, 626-11 Minaminakano, Minuma-ku, Saitama city, Saitama, 337-0042, Japan. E-mail: [email protected].
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Appendix 1. Exact English Translation of the Questionnaire 1. 2. 3. 4. 5.
Do Do Do Do Do
2063.e1
you you you you you
have have have have have
ocular fatigue? uncomfortable sensation in your eye? heavy sensation in your eye? discharge? itching sensation in your eye?
6. 7. 8. 9. 10. 11. 12. 13. 14.
Do Do Do Do Do Do Do Do Do
you you you you you you you you you
have have have have have have have have have
sticky sensation in your eye? glare? excessive blinking? dryness in your eye? pain in your eye? foreign body sensation in your eye? epiphora? redness in your eye? a history of chalazion or hordeolum?