Assessment of Meibomian Gland Function in Dry Eye Using Meibometry

CLINICAL SCIENCES Assessment of Meibomian Gland Function in Dry Eye Using Meibometry

Norihiko Yokoi, MD, PhD; Federico Mossa, MD; John M. Tiffany, PhD; Anthony J. Bron, FRCOphth

Objective: To study meibomian gland function in dry eye, and 268.5 ± 6.3 for controls, showing lower val- eyes using meibometry. ues in the MGD group relative to all others (PϽ.001). Results of IM gave similar results (PϽ.001, P = .01, Methods: Forty-two patients with clinically diagnosed and PϽ.001, respectively). Lipid layers appeared lower dry eye that was reclassified as meibomian gland dys- for the MGD group than others. function (MGD [n = 12]), aqueous-tear deficiency (AD [n = 10]), MGD combined with AD (n = 2), “incom- Conclusions: Compared with controls, lid lipid levels plete” dry eye (n = 12), and non–dry eye (6 eyes) were are reduced in patients with MGD, and increased in compared with 41 healthy control subjects. The follow- women with AD. Lipid layer thickness is increased in ing 2 techniques of meibometry were applied: direct mei- women with AD compared with patients with MGD. Both bometry (DM) measuring lipid imprints using the Mei- meibometric techniques may be useful for evaluating bometer, and integrated meibometry (IM) using image- MGD. Although DM requires special equipment (the Mei- scanning and computer densitometry. Tear film lipid layer bometer), it provides a record of immediate diagnostic thickness was assessed using interference microscopy. value. Although IM is less effective than DM, it offers visual documentation of the lipid imprint, which may it- Results: Imprints were homogeneous for all subjects self be of diagnostic value, and uses equipment avail- except those with MGD. Mean ± SE readings on able in many laboratories. results of DM were 127.24 ± 24.4 for MGD, 306.4 ± 9.2 for AD, 248.6 ± 13.2 for incomplete dry Arch Ophthalmol. 1999;117:723-729

EIBOMIAN gland dis- tear evaporation and ocular surface dam- ease is a common con- age due to increased osmolality.8,10,11 dition that is often It is important to be able to classify symptomatic.1,2 Meibo- and quantify MGD for diagnostic reasons mian gland dysfunc- and to observe the effects of treatment. The tion (MGD) is a term adopted by Jester et diagnosis of MGD is difficult, but various M3 al chiefly to describe obstructive meibo- methods are now available to assess mei- mian gland disease. The primary disease bomian gland status. Simple clinical tests is common, but there is a strong associa- include grading the clinical features of mei- tion between MGD and certain forms of bomian gland disease1 and grading the ex- skin disease such as atopic and sebor- pressibility and quality of the meibomian rheic dermatitis and acne rosacea.4 It also oil.1,12 More specialized methods are the may be caused by systemic retinoid detection of “gland dropout” using mei- therapy5 or less commonly by polychlor- bography1,2,10-13 and the measurement of From the Department of inated biphenyl.6 Obstructive MGD may casual oil levels at the lid margin and lipid Ophthalmology, Kyoto be focal, with patchy involvement of delivery rate using meibometry.14-16 In ad- Prefectural University of glands, or diffuse, when oil expression is dition, thickness of the preocular oil layer Medicine, Kyoto, Japan impaired in all glands.7 Cicatricial and non- can be gauged using interferometry,17-19 (Dr Yokoi), and Nuffield cicatricial forms of MGD exist.7 and evaporative water loss can be mea- Laboratory of Ophthalmology, Obstructive MGD may give rise to sured using evaporimetry.10,20,21 University of Oxford, Oxford, symptoms directly, because of local lid Meibometry is a simple test for quan- England (Drs Mossa, Tiffany, margin changes, or indirectly, by induc- tifying the amount of lipid at the lid mar- and Bron). The authors do not 8 have any commercial or ing an evaporative dry eye. It is consid- gin and has been used successfully in 15 proprietary interest in any ered to be the major cause of evaporative healthy subjects. It involves the blot- product or company discussed dry eye.9 In this condition, a decreased de- ting of lipid onto a loop of translucent plas- herein. livery of meibomian oil causes increased tic tape from the central region of the lower

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 PARTICIPANTS AND METHODS INTEGRATED MEIBOMETRY Integrated meibometry (IM) is performed on the imprint ob- STANDARD MEIBOMETRY tained by DM. Immediately after the meibometry reading, the tape loop is opened and attached to a strip of exposed Standard meibometry uses the clinical Meibometer (MB 35-mm negative film to provide a black backing. The blot 550; Courage & Khazaka Electronic GmbH, Cologne, Ger- appears as a dark line on the uniform gray tape (Figure 2). many). Lipid is blotted from the central third of the lower The oil imprint is scanned using a handheld scanner (Scan- lid with a force of 15 g onto a handheld loop of plastic tape Man; Logitech Inc, Fremont, Calif) into a computer (Mac- 8 mm wide, supplied by the manufacturers. Contact is intosh PowerBook 5300cs; Apple Computers Inc, Cuper- maintained for 10 seconds. The oil creates a translucent tino, Calif) for densitometric analysis using the Scananalysis band across the tape. The tape is then scanned across the densitometric program (Biosoft, Cambridge, England). An reading window of the photosensor of the Meibometer, automated background subtraction method is applied. The and the maximum reading is taken from the densest part program provides an integrated analysis of densities over the of the blot as it passes the line of the window.14-16 In whole area of the imprint. To prevent spread of oil over the healthy subjects with an even distribution of meibomian tape in warm weather, tapes were scanned as soon as pos- oil, the readings have been used to calculate average rest- sible after the DM reading. ing values for meibomian lipid at the lid margin (the For this study, DM and IM readouts are given in arbi- casual level).15 trary instrument units, and all measurements were performed 5 times and averaged. All data are given as mean ± SE. DIRECT MEIBOMETRY PARTICIPANTS The standard technique of meibometry was modified as follows (ie, direct meibometry [DM]). A preformed loop After explanation of all procedures and with fully of meibometry tape is placed in the reading head of the informed consent, 42 patients (8 men and 34 women; Meibometer to establish the zero reading. The loop is mean age, 63.4 ± 2.2 years) who had received a clinical formed by heat-sealing the tape at a predetermined point diagnosis of dry eye were recruited from the external to give a loop length of 20 mm. The handle is clipped to disease clinic. An additional 41 healthy control subjects the prism housing of a Goldman applanation tonometer (16 men and 25 women; mean age, 56.4 ± 2.1 years) (Keeler, Windsor, England) mounted on the slitlamp were enrolled into the study. Exclusion criteria for con- biomicroscope. This permits controlled placement of trols were biomicroscopic abnormality of the cornea, the probe on the lid margin under direct vision. The conjunctiva, or meibomian glands; lacrimal drainage tonometer is set at zero for each impression. With the problems; signs of dry eye; and a history of contact lens subject looking upward without blinking, the lower lid wear or use of eye drops for any reason during the pre- is gently everted (avoiding stretching, which might ceding 3 months. This research conformed to the tenets express oil), and the loop is pressed onto the central of the Declaration of Helsinki and was approved by Cen- third of the lid margin with sufficient pressure to obtain tral Oxford Research Ethics Committee, Oxford Univer- an imprint across the width of the tape, without bending sity, Oxford, England. the handle of the loop. A line of contact is seen across the full width of the tape (Figure 1), and contact is ASSESSMENT OF THE LID MARGIN maintained for 3 seconds. After blotting, the tape is kept AND OCULAR SURFACE in air for 3 minutes to allow evaporation of any tears picked up from the lid. The loop is placed in the reading The following assessments were made successively on the head of the Meibometer, and a reading is taken in the left eye of all subjects. The order of the test was chosen to standard way. minimize the effect of one test on succeeding tests. First,

lid. An index of the resting amount of lipid on the lid the sampled area, which could result in erratically low margin (the casual level) is obtained by a spot photo- meibometry values in patients with MGD. metric reading taken from the center of the lipid im- We therefore devised 2 modifications to the stan- print.14,15 The technique has been used to establish nor- dard meibometry technique, which allowed us to assess mal casual levels for male and female subjects across the the full range of oil deposition on a segment of the lid age span.15 The use of meibometry for the diagnosis of margin. We herein describe the methods and their ap- MGD is of interest, but the standard technique has cer- plication to the study of a mixed population of patients tain disadvantages. The tape used is 8 mm wide and with dry eye. samples the pool of oil along the central third of the lower lid margin (and also the corresponding region of the up- RESULTS per lid, since lipid is exchanged during eye closure). Mei- bomian gland dysfunction may be focal or diffuse, and CLASSIFICATION OF DRY EYE therefore there is a possibility that the sampled area will not represent changes along the full extent of the lid. A Following clinical examination of the 42 patients with related consideration is that patchy, focal, obstructive dis- diagnosis of dry eye, 36 diagnoses were reclassified as ease along the central third of the upper and lower lids MGD (n = 12 [6 men and 6 women]; mean age, 70.0 ± could give rise to a nonuniform distribution of oil over 3.6 years), AD (n = 10 [all women]; mean age, 54.7 ± 4.5

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 observation and classification of tear lipid interference pat- “incomplete” (ID), or AD combined with MGD. The diag- terns were as previously reported.22 Second, biomicro- nosis of AD was based on abnormal results of tear flow or scopic lid margin abnormalities (including irregularity of volume assessments (Schirmer I [Յ5 mm] or cotton-thread lid margin, vascularity, plugging of meibomian orifices, and test [Յ10 mm]), an arbitrary score of 2 or greater for sur- retroplacement of mucocutaneous junction using a modi- face staining using the Oxford grading scheme,24,25 and nor- fication of the approach reported elsewhere)1 were scored. mal oil expression. The diagnosis of MGD was based on ab- Signs were evaluated as positive or negative, a positive score normal findings on the lid marsh (Ͼ3 positive findings1), being applied when the finding was regarded as promi- reduced oil expression (a negative score), an Oxford stain- nent. Third, lipid sampling using meibometry was per- ing grade of 2 or greater, but no abnormalities in the Schirmer formed. Fourth, after an interval of at least 5 minutes, the and cotton-thread test results. Diagnosis of ID was based on cotton-thread test23 (measurement of wetted length for 15 the presence of abnormal tear breakup time (Յ5 seconds), seconds with the eye open and blinking normally) was per- abnormal ocular surface staining (Ͼ2), normal results of the formed. Fifth, results of ocular surface fluorescein stain- Schirmer and cotton-thread tests, normal oil expression from ing using the Oxford grading system were evaluated.24 A the middle third of the lower lid (positive score), and 3 or Fluoret paper (Chauvin Pharmaceuticals Ltd, Romford, En- fewer biomicroscopic features of MGD on the lid margin.1 gland) is wetted with a single drop of unpreserved, iso- This group could include patients with a minor degree of tonic sodium chloride (Minims, Chauvin Pharmaceuti- MGD. Tear breakup time was not an entry criterion, but mean cals Ltd), shaken free of excess fluid, and touched gently times were 3 seconds or less in each diagnostic group onto the lateral tarsal plate. The field is illuminated with (Table 1). blue light from the slitlamp and observed through a yel- low barrier filter (Kodak Wratten 12; Eastman Kodak Co, CLASSIFICATION OF TEAR LIPID LAYER Rochester, NY), which allows staining of cornea and con- INTERFERENCE PATTERNS junctiva to be compared with a series of staining grades represented on a standard chart.25 A grade of 0 to 5 was as- Tear lipid interference colors were observed using inter- signed to each of the 2 exposed conjunctival zones and to ferometry in a 2-mm diameter zone of the central cornea. the cornea, and the 3 grades were summed to give a total The interference colors were recorded with a videocas- maximum score of 15. Sixth, tear breakup time was mea- sette recorder (C-14VT20; Sanyo Electric Co, Osaka, Ja- sured.26 Seventh, Schirmer I test27 without anesthesia (pa- pan) and later classified into the following grades22: grade pers inserted laterally; eyes open and blinking spontane- 1 indicates a somewhat gray color with uniform distribu- ously) was performed. Finally, meibomian gland expression tion; grade 2, a somewhat gray color with nonuniform dis- was performed with distal pressure applied moderately tribution; grade 3, a few colors with nonuniform distribu- through the tarsus of the central third of the lower eye- tion; grade 4, many colors with nonuniform distribution; lid.2,12 Expression was evaluated as positive or negative by and grade 5, corneal surface partially exposed. one of us (F.M.) throughout the study; a negative value was assigned where application of moderate distal pressure STATISTICAL ANALYSIS showed a partial or total lack of expression from the glands in the central third of the lower lid. A positive value was The results were expressed as mean ± SE, and the values ob- assigned when there was complete and uniform expres- tained for each group were compared using a 1-way analysis sion of oil. Oil quality (ie, clarity) was not evaluated to avoid of variance (ANOVA) and Scheffe´ test with respect to DM or adding a further subjective element to the observation. IM values. The Mann-Whitney test was used to compare the distribution of interference grades and DM between 2 groups. CLASSIFICATION OF DRY EYE Simple regression analysis was used to compare DM with IM findings. The Fisher exact probability test was also used to Following examination of patients as described above, dry compare the distribution of interference grades. A P value of eye was classified as MGD, aqueous tear-deficient (AD), .05 or less was considered to be significant.

years), ID (n = 12 [2 men and 10 women]; mean age, 65.2 ues were statistically lower in the MGD group com- ± 3.6 years), and MGD plus AD (n = 2 [1 man and 1 pared with the AD, ID, and control groups (Scheffe´ test, woman]; aged 71 and 80 years, respectively). Eyes in the PϽ.001 for each). Two patients had combined AD and remaining 6 patients (6 women; mean age, 55.8 ± 5.5 MGD. Of these, the man showed a faint oil imprint and years) regarded clinically as having dry eye could not be a marked reduction in meibometry readings using both classified as such at the time of assessment. Dry eye data techniques. In the woman, the oil imprint was spotty and for all groups are summarized in Table 1. In all patients irregular, but showed a reduction on results of DM alone. with MGD, the findings in the upper lid were fully con- Casual oil levels were statistically higher in the AD group sistent with those in the lower lid. (all women) than in the female control group. Results are shown in Figure 3 and Table 2. CASUAL OIL LEVEL USING DM CASUAL OIL LEVEL USING IM Mean casual oil levels measured using DM in each group were 127.2 ± 24.4 U in the MGD group, 306.4 ± 9.2 U in Before the densitometric analysis, the oil imprints were the AD group, 248.6 ± 13.2 U in the ID group, and 268.5 qualitatively assessed for regularity and homogeneity. Rep- ± 6.3 U in the control group. There was a significant dif- resentative images are shown in Figure 2. Meibomian im- ference among the 4 groups (ANOVA, PϽ.001); the val- prints from the MGD group showed partial blots of oil

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 across the tape, with irregularity in 9 patients (75%) and tribute to this result, the loss of data due to the limited a faint, diffuse imprint in 3 (25%). However, in the other reading window when using DM may also be a factor. groups, there were more homogeneous blots with fewer irregularities, and there were only 2 patients (17%) with CLASSIFICATION OF TEAR LIPID LAYER slight irregularity in the AD group and no irregularity in INTERFERENCE PATTERNS the control group. In the ID group, there was 1 patient (8%) with some irregularity. Meibomian gland dysfunction was classified as grades 2 Mean casual oil levels measured using densitom- (6 eyes) and 3 (6 eyes), whereas AD was classified as etry in each group, expressed as raw values divided by grades 2 (1 eye), 3 (3 eyes), 4 (4 eyes), and 5 (2 eyes). 100, were 450.6 ± 51.7 in the MGD group, 1082.3 ± 135.1 Incomplete dry eye was classified as grades 2 (5 eyes), 3 in the AD group, 806.8 ± 91.5 in the ID group, and 913.1 (5 eyes), and 4 (2 eyes). There was a significant differ- ± 31.6 in the control group. In the blots used for densi- ence in the distribution of grades between the MGD and tometry, the pixel density was always less than the maxi- AD (P = .001) and between the AD and ID groups (P = .02), mum represented by the black backing film, ie, there was and no difference was found between the MGD and ID no saturation of the image. There was a significant dif- groups (P = .36). ference among the 4 groups (ANOVA, PϽ.001); the values were significantly lower in the MGD group com- COMMENT pared with the AD, ID, and control groups (Scheffe´ test, PϽ.001, P = .01, and PϽ.001, respectively). Results are Our study examined the meibomian oil of the tear film shown in Figure 4, and distribution of age and meibo- and lid margin using interferometry and meibometry in metric results with respect to sex are also summarized a selected population of patients with dry eye. A propor- in Table 2. tion of patients with AD is known to suffer from meibomian gland obstruction,28 and in our study, patients with RELATIONSHIP BETWEEN DM AND IM MGD were distinguished from those with AD alone (or with only minor degrees of MGD). It is generally ac- In the control group, there was a significant linear cor- cepted that the effect of obstructive meibomian gland dis- relation between DM and IM (R2 = 0.35 [PϽ.001]). In the ease, the chief cause of evaporative dry eye,9 arises from MGD, AD, and ID groups, in contrast, there was no sig- a loss of barrier function of the preocular lipid, due to nificant correlation between DM and IM (R2 = 0.19 qualitative or quantitative changes in the meibomian se- [P = .15], R2 = 0.11 [P = .36], and R2 = 0.20 [P = .08], re- cretion.1,2,29-31 Previous studies in healthy subjects have spectively). Although small sample numbers may con- suggested that the amount of meibomian oil distributed along the lid margins (about 300 µg) provides an ample reservoir for distribution over the preocular tear film (9 µg).14 Such studies have failed, however, to show a cor-

A B C D

Figure 2. Representative examples of oil imprints from a healthy control subject (A), 2 patients with meibomian gland dysfunction (B and C), and a Figure 1. A view of the system for taking oil imprints from the lid margin. patient with aqueous-deficient dry eye (D). Part B shows an irregular imprint; The imprint is clearly seen. part C, a faint imprint.

Table 1. Results of Dry Eye Examinations*

Interference Positive Results of No. of Grading of Tear Lid Margin Cotton-Thread Test, Fluorescein Tear Breakup Schirmer I Test, Negative Lipid Group Patients Lipid Layer Findings mm per 15 s Staining Score Time, s mm per 5 min Expression MGD 12 2.5 ± 0.2 4.0 ± 0.0 26.1 ± 3.5 3.2 ± 0.8 2.5 ± 0.2 16.3 ± 2.6 12 AD 10 3.7 ± 0.3 0.9 ± 0.4 12.3 ± 2.5 7.9 ± 1.3 2.1 ± 0.3 1.5 ± 0.6 0 ID 12 2.7 ± 0.2 1.5 ± 0.5 21.2 ± 1.8 4.1 ± 0.8 3.0 ± 0.3 19.5 ± 3.3 0 AD + MGD 2 3.5 ± 1.5 3.5 ± 0.5 10.5 ± 2.5 4.5 ± 2.5 2.0 ± 1.0 2.0 ± 2.0 2

*Unless otherwise indicated, data are given as mean ± SE (for AD + MGD, mean ± range). MGD indicates meibomian gland dysfunction; AD, aqueous tear deficiency; and ID, “incomplete” dry eye. Positive lid margin findings include irregularity of lid margin, vascularity, plugging of meibomian orifices, and retroplacement of mucocutaneous junction. Fluorescein staining scores were summed between cornea and conjunctiva. Scores and findings are described in the “Assessment of the Lid Margin and Ocular Surface” subsection of the “Patients and Methods” section.

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 relation between the size of the lid margin reservoir and anticipated that this would provide a more complete the preocular lipid thickness, although there is a posi- description of lipid amount and distribution on the tive trend.32 It is intuitive, however, that obstructive MGD sampled region of the lid. However, in its present form, of sufficient degree will cause a measurable reduction in IM does not measure transmission in the same manner lid margin oil and that, at some point, this will be re- as does DM. This may account for some discrepancies flected by a reduced delivery of lipid to the tear film. Our in our findings. study supports this hypothesis. There was an excellent correlation between values The 2 meibometric techniques that we used evolved obtained using DM and IM in controls (R2 = 0.35; from standard meibometry, in which the uptake of lipid PϽ.001), but there was loss of agreement when these onto the sampling tape is achieved by applying the hand- techniques were used in the MGD group (R2 = 0.19; held tape to the lid with a standard force of 15 g for a P = .15). Although the lack of correlation between mea- duration of 10 seconds. The revised technique used herein surements made on identical imprints could reflect the applied the least force required to create an imprint loss of data predicted with irregular imprints using DM, under direct vision. By reducing the time of application it was only with this technique that we were able to to 3 seconds, we reduced the risk of contamination of show a significant difference in lipid values between the imprint with tears, which can occur with more pro- women with AD and female controls on the one hand, longed application. Comparison of DM with IM has and women with ID on the other (Table 2), which sug- been facilitated by analyzing identical imprints by each gested that DM was providing more information in these technique. situations. We presume that the most likely cause for Like standard meibometry, DM measures peak this discrepancy is that information is lost in the scan- transmission only within a narrow band across the ning process in IM. The major findings of our study imprint. The IM technique integrates area and transmis- were that, compared with controls, lid lipid levels are sion over the whole extent of the imprint, and we reduced in MGD in both sexes; lid lipid levels are increased in women with AD; and preocular tear film

400 lipid thickness is increased in women with AD compared with patients with MGD. Using either form of meibometry, casual oil levels were quantitatively lower in patients with obstructive

300 MGD than in controls, patients with AD without marked MGD, or patients with ID. Levels in MGD were about half those found in controls (Table 2). These findings are in keeping with the decreased meibomian lipid expres- 200 sion from the central third of the lid in this group of patients, which was a diagnostic criterion for MGD. Be- cause meibometry in its present form is an incomplete sampling technique (confined to the central part of the 100 lid), we recognize that the failure to show a fall would Spot MeibometryArbitrary Value, Units not exclude the presence of significant disease. Further study of a larger, more representative sample of patients with MGD would appear to be justified to explore the 0 scope of the technique. MGD AD ID Controls Meibometry and meibomian expression are not Figure 3. Comparison of direct meibometry readings in healthy control equivalent techniques. Meibometry records the natural subjects and patients with dry eye. The values were significantly lower in level of lipid on the lid margin in response to the nor- patients with meibomian gland dysfunction (MGD) than in those with aqueous deficiency (AD) or “incomplete” dry eye (ID) and controls mal conditions of delivery, whereas expression records (all, PϽ.001). Values are shown as mean ± SE. the ability to achieve visible delivery by increasing in-

Table 2. Results of Meibometry in Each Group*

Age, y Direct Meibometry Integrated Meibometry Patients, Group No. M/F Men Women Men Women Men Women MGD 6:6 69.0 ± 7.1 71.0 ± 2.8 161.4 ± 40.5 93.0 ± 22.4 498.2 ± 69.1 402.9 ± 78.1 AD 0:10 NA 54.7 ± 4.5 NA 306.4 ± 9.2†‡ NA 1082.3 ± 135.1§࿣ ID 2:10 54.5 ± 7.5 67.3 ± 3.8 264.3 ± 29.7 245.4 ± 15.2‡ 671.8 ± 283.6 833.8 ± 100.1࿣ AD + MGD 1:1 71 80 23.3 119.6 90.7 958.0 Control 16:25 58.5 ± 2.6 53.1 ± 3.5 266.6 ± 10.6 269.7 ± 7.9† 891.2 ± 34.7 949.2 ± 60.7§

*Unless otherwise indicated, data are given as mean ± SE. MGD indicates meibomian gland dysfunction; AD, aqueous deficiency; ID, “incomplete” dry eye; and NA, not applicable because the AD group consisted of women only. †P = .01, vs female controls undergoing direct meibometry. ‡P = .008, vs women with ID undergoing direct meibometry. §P = .06, vs female controls undergoing integrated meibometry. ࿣P = .15, vs women with ID undergoing integrated meibometry.

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©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 1400 ings. Another explanation is that the hyperemic lid margin of the patient with dry eye is at a higher temperature than normal, leading to greater oil fluidity. This could in- 1200 fluence the level of oil on the lid margin and the ease of transfer onto the tear film. Since a minor degree of ptosis 1000 is common in patients with dry eye, it should also be considered that a thickening of the preocular oil film could be 800 due to a reduced interpalpebral area. In our study, assessment of interference patterns of the tear lipid layer showed

600 that a thicker layer (grade 4) was more frequently present in patients with AD (who were lipid sufficient) than in lipid- deficient (aqueous-sufficient) patients with MGD (P = .03). 400 This is consistent with the difference in casual oil levels in

Integrated MeibometryArbitrary Value, Units these groups of patients shown on results of DM and IM. 200 It must be anticipated that in patients with dry eye with combined AD and MGD, oil gland obstruction will come 0 to dominate the picture. MGD AD ID Controls We found that in patients with MGD, imprints were Figure 4. Comparison of integrated meibometry readings in healthy control invariably irregular and incomplete compared with the subjects and patients with dry eye. The values were significantly lower in patients with meibomian gland dysfunction (MGD) than in those with uniform band-shaped imprint achieved in controls. It may aqueous deficiency (AD) or “incomplete” dry eye (ID) and controls ( PϽ.001, be that simple observation of the imprint with the na- P = .01, and P = .02, respectively). Values are shown as mean ± SE. ked eye would be a useful, rough-and-ready way of de- tecting reduced oil delivery. Direct and integrated mei- traductal pressure. Although we may reasonably expect bometry were able to demonstrate a quantitative reduction reduced casual levels to equate with reduced express- of meibomian oil in the selected patients with MGD un- ibility, the reverse is not necessarily the case; increased dergoing assessment. Both techniques were found to be expressibility (the criterion for meibomian seborrhea) of diagnostic value. Direct meibometry was easier to per- could indicate hypersecretion or the release of secre- form and offers data of immediate significance in a clini- tions dammed back by partial obstruction.7 Meibom- cal setting. Integrated meibometry involves the use of a etry and expressibility are in fact complementary tests, scanner and a computer with software for densitometric since theoretically, at least, they could distinguish a hy- analysis. It offers excellent visual documentation and use- persecretory state as one in which the casual level and ful additional information, and is therefore recom- expressibility are higher than normal. Expression also mended when reviewing clinical data. We are presently gives additional information concerning the quality of ex- generating normative data for this technique. pressed oil.1,12 In 1997, Lee and Tseng33 demonstrated distinctive As shown in Table 2, a significantly higher casual ocular surface changes in patients with MGD, including oil level was demonstrated using DM in women with AD rose bengal staining in the nonexposed portion of the in- compared with controls with a similar age distribution ferior bulbar conjunctiva and a “lytic” shape on results (P = .01); the same trend was seen using IM, but did not of impression cytology. Our patients did not undergo as- reach significance (P = .06). The oil levels were also sig- sessment from this point of view, but it will be of inter- nificantly lower using DM in women with ID compared est to relate lid and preocular oil availability to such with women with AD (P = .008). This difference is not changes in the future. explained by the greater age of patients in the ID group, since in male and female controls, meibometry readings Accepted for publication January 6, 1999. rise with age.15 The difference between AD and ID val- We thank Elaine Grande and Paul Parker for their tech- ues was not shown using IM (P = .15). Table 2 shows that nical assistance in preparing photographs, and all the sub- meibometry values in the ID group were lower than in jects who participated in the study. the control group using either method of analysis, al- Reprints: Anthony J. Bron, FRCOphth, Nuffield Labo- though this difference did not reach significance. The ID ratory of Ophthalmology, University of Oxford, Walton group could include patients with a minor degree of MGD. Street, Oxford OX2 6WA, England (e-mail: anthony Although it is not possible from our data to infer that oil [email protected]). deficiency in this group contributed to its clinical features, the possibility does exist. REFERENCES In a previous study using interferometry, it was observed that the tear lipid layer was thicker in the preocu- 19,22 1. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease: classification and lar tear film of patients with AD than in controls. It was grading of lid changes. Eye. 1991;5:395-411. hypothesized then that the lower aqueous tear volume in 2. Shimazaki J, Sakata M, Tsubota K. Ocular surface changes and discomfort in patients with AD and consequent reduction in the for- patients with meibomian gland dysfunction. Arch Ophthalmol. 1995;113:1266- ward displacement of lid oil as the tear film was com- 1270. 3. 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Correction

Error in Byline. In the article titled “Ischemic Scalp Necrosis Preceding Loss of Visual Acuity in Giant Cell Arteritis,” in the December issue of the ARCHIVES (Arch Ophthalmol. 1998;116:1690-1691), there were 2 errors in the byline. The MD degree was omitted for Robert C. Sergott, and Ralph C. Eagle, Jr, MD, was omitted from the list of authors. The journal regrets the errors.

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