Jpn J Ophthalmol (2012) 56:14–19 DOI 10.1007/s10384-011-0103-6
CLINICAL INVESTIGATION
Association of contact lens-related allergic conjunctivitis with changes in the morphology of meibomian glands Reiko Arita • Kouzo Itoh • Shuji Maeda Koshi Maeda • Atsuo Tomidokoro • Shiro Amano
•
Received: 24 March 2011 / Accepted: 5 October 2011 / Published online: 23 November 2011 Ó Japanese Ophthalmological Society 2011
Abstract Purpose To observe morphological changes in the meibomian glands of patients with contact lens-related allergic conjunctivitis (CLAC) and to assess the relations between the morphological changes and eyelid and tear film parameters. Methods We observed subjects in four groups: 64 eyes of 64 contact lens (CL) wearers with CLAC, 77 eyes of 77 CL wearers without CLAC, 55 eyes of 55 patients with perennial allergic conjunctivitis (perennial AC), and 47 eyes of 47 healthy volunteers. The following tests were performed: slit-lamp examination, measurement of tear film breakup time, grading of morphological changes in meibomian glands (meiboscore) as assessed by noncontact meibography, grading of meibomian gland distortion in meibography, tear production as assessed by Schirmer’s I test, and grading of meibum expression. Results The mean score for meibomian gland distortion was significantly higher in the CL wearers with CLAC than in the CL wearers without CLAC (p \ 0.0001); it was also significantly higher in the non-CL wearers with perennial AC than in the non-CL wearers without perennial AC (p \ 0.0001). There was no significant difference between
R. Arita (&) K. Itoh Itoh Clinic, 626-11 Minaminakano, Minuma-ku, Saitama, Saitama 337-0042, Japan e-mail:
[email protected] R. Arita A. Tomidokoro S. Amano Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan S. Maeda K. Maeda Maeda Ophthalmic Clinic, 3-30 Nakamachi, Aizuwakamatsu, Fukushima, Japan
123
the mean scores for meibomian gland distortion of the nonCL wearers with perennial AC and the CL wearers with CLAC (p = 0.27). The score for meibomian gland distortion was significantly positively correlated with the meibum score in the CL wearers with CLAC and with the meiboscore in the CL wearers without CLAC. Conclusion CLAC is associated with an increase in meibomian gland distortion. Allergic reaction, rather than CL wear, appears to be responsible for the increase in meibomian gland distortion in patients with CLAC. Keywords Contact lens Allergic conjunctivitis Meibomian glands Meibography
Introduction Contact lens-related allergic conjunctivitis (CLAC) is a common cause of ocular discomfort in contact lens wearers, which sometimes causes contact lens (CL) intolerance. CLAC inflammation induces various reactions and symptoms, such as papillary formation, conjunctival hyperemia, mucus discharge, and itchy sensations. Severe CLAC involves the formation of giant papillary conjunctivitis (GPC), which is reported to be associated with decreased meibomian gland function [1]. Mathers and Billborough [1] report that CL wearers with GPC have significantly more meibomian gland dropout and greater meibum viscosity than those without GPC. Moreover, allergic conjunctivitis (AC) without CL is also reported to be associated with tear film instability and dry eye [2, 3]. Toda et al. [2] report that AC decreases goblet cell density, which leads to tear film instability. Suzuki et al. [3] report that seasonal AC is associated with advanced tear instability and thickening of the tear film lipid layer. Because the conjunctival tissue lies adjacent to
Allergy and meibomian glands
the meibomian glands, CLAC may also affect the meibomian glands [4, 5], resulting in tear film instability. The purpose of the present study was to observe the morphological changes in the meibomian glands of patients with CLAC using noncontact meibography [6], and to assess the relations between the morphological changes and eyelid and tear film parameters.
Subjects and methods Subjects The subjects comprised four groups: 64 eyes of 64 CL wearers with CLAC (32 men and 32 women; mean age 31.1 ± 9.4 years), 77 eyes of 77 CL wearers without CLAC (31 men and 46 women; 32.5 ± 8.1 years old), 55 eyes of 55 patients with perennial AC (29 men and 26 women; 32.3 ± 15.0 years), and 47 eyes of 47 healthy volunteers (22 men and 25 women; 32.8 ± 9.5 years). Perennial AC was diagnosed both in the non-CL wearers and the CL wearers based on complaints of an itchy sensation and observation of papillary formation in the conjunctiva. Exclusion criteria for the AC and control groups included blepharitis, obvious eyelid or ocular surface disorders, CL wear, continuous eye drop use, history of eye surgery, and either systemic or ocular diseases that could interfere with either tear film production or function. Data used in this study were obtained from the right eye of each subject. When the right eye (but not the left eye) was excluded from the study, data from the left eye were used. Written informed consent was obtained from all subjects before examination. When subjects were younger than 20 years of age, written informed consent was obtained from their parents. This study was approved by the institutional review board of Itoh Clinic and adhered to the tenets of the Declaration of Helsinki. Examinations After CL removal, the following tests were performed sequentially: a slit-lamp examination of the cornea and conjunctiva both before and after fluorescein staining, measurement of tear film breakup time (BUT), meibography, tear production by Schirmer’s I test, and grading of meibum expression. Superficial punctate keratopathy in the cornea was scored from 0 to 3. Tear film BUT was measured three 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 (meiboscore) for
15
each eyelid, as previously described [6]: grade 0: no loss of meibomian glands, grade 1: area of loss \1/3 of the total area of meibomian glands, grade 2: area of loss between 1/3 and 2/3 of the total area, grade 3: area of loss [2/3 of the total area. Meiboscores for the upper and lower eyelids were summed to obtain a score between 0 and 6 for each eye. The presence of distortion was determined when distortion of [45° in at least one meibomian gland in the upper or lower eyelid was confirmed by meibography. Meibomian gland (MG) distortion score was graded for MG distortion in the upper eyelid from 0 to 2; grade 0: no distortion of the meibomian glands; grade 1: 1–4 meibomian glands with distortion; grade 2: more than five MGs with distortion (Fig. 1). Tear film production was evaluated by Schirmer’s test without applying topical anesthetic. Digital pressure was applied to the upper tarsus, and the degree of ease with which meibomian secretion (meibum) was expressed was evaluated semiquantitatively as follows [7]: grade 0, clear meibum that was expressed easily; grade 1, cloudy meibum that was expressed with mild pressure; grade 2, cloudy meibum that was expressed with more than moderate pressure; and grade 3, meibum that was not expressed, even with hard pressure. The unpaired t test and Mann–Whitney U test were used to compare variables between the two groups. Spearman correlation analysis was used to examine the correlation between the MG distortion score and the other parameters in subjects wearing contact lens both with and without allergic conjunctivitis. Kruskal– Wallis test or analysis of variance (ANOVA) was used to compare variables among three or more groups. The Tukey–Kramer test was used as a post hoc test after ANOVA. The Mann–Whitney U test with Bonferroni’s correction for multiple comparisons was used as a post hoc test after the Kruskal–Wallis test. A probability level of \0.05 was considered statistically significant.
Statement of ethics We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research.
Results Mean age (p = 0.72) and sex ratio (p = 0.50) did not differ significantly among the four groups. In the CLAC group, 16 patients used rigid gas-permeable lenses and 48 patients used hydrogel lenses (conventional hydrogel lenses, n = 8; disposable hydrogel lenses, n = 40). In the CL wearers without CLAC, 28 patients used rigid
123
16
R. Arita et al.
Fig. 1 Representative cases of each grade of meibomian gland distortion, scored using the following grades: grade 0, no distortion; grade 1, 1–4 distortions;grade 2, more than five distortions
grade 0
grade 1 grade 2
gas-permeable lenses and 49 used hydrogel lenses (conventional hydrogel lenses, n = 11; disposable hydrogel lenses, n = 38). The ratio of rigid gas-permeable lens wearers to hydrogel lens wearers did not differ significantly between CL wearers with and those without CLAC (p = 0.22). The average duration of CL wear among CL wearers with CLAC was 11.2 ± 8.2 years, and 13.1 ± 7.3 years in those without CLAC (p = 0.16). Comparison of the meibomian gland changes and tear film-related factors among the four groups Table 1 shows the results of the examinations in the four groups. There were no significant differences in the meibum scores (p = 0.25, Kruskal–Wallis test), meiboscores (p = 0.051, Kruskal–Wallis test), or Schirmer’s values (p = 0.16, ANOVA) among the four groups. The BUT (p = 0.0002, ANOVA) and superficial punctate keratopathy scores (p \ 0.0001, Kruskal–Wallis test) differed significantly among the four groups. The BUT was significantly shorter in the CL wearers without CLAC than in the normal volunteers (p = 0.0002, Tukey–Kramer test). The superficial punctate keratopathy scores were significantly lower in the normal volunteers than in the patients with perennial AC (p = 0.0076) and in the CL wearers without CLAC (p \ 0.0001). In all four groups, all MG distortions were observed in the upper eyelid (Fig. 2). Table 2 shows a comparison of
123
the MG distortion scores. The mean MG distortion score was significantly higher in the CL wearers with CLAC than in the CL wearers without CLAC (p \ 0.0001). The mean MG distortion scores were significantly higher in the nonCL wearers with perennial AC than in the non-CL wearers without perennial AC (p \ 0.0001). There was no significant difference between the mean MG distortion scores of the non-CL wearers with perennial AC and the CL wearers with CLAC (p = 0.27). In the CL wearers with CLAC, there was no significant difference between the mean MG distortion scores of the 16 rigid gas-permeable lens wearers (0.31 ± 0.70) and the 48 hydrogel lens wearers (0.63 ± 0.84) (p = 0.15); nor was there any significant difference between the mean MG distortion scores of the 28 rigid gas-permeable lens wearers (0.036 ± 0.19) without CLAC and the 49 hydrogel lens wearers (0.12 ± 0.39) without CLAC (p = 0.29). Correlations between the meibomian gland distortion score and other factors in CL wearers Table 3 shows the results of a Spearman correlation analysis between the MG distortion scores and the other parameters in contact lens wearers with or without allergic conjunctivitis. The MG distortion score showed significantly positive correlations with meibum score in CL wearers with CLAC and with meiboscore in CL wearers without CLAC.
Allergy and meibomian glands
17
Table 1 Mean (±standard deviation) values of parameters in each group CL wear ?
Parameters
AC? (n = 64) BUT (s) Schirmer’s value (mm)
CL wear AC- (n = 77)
AC? (n = 55)
p value AC- (n = 47)
4.3 ± 2.1
4.1 ± 2.1
5.2 ± 2.4
5.3 ± 2.1
15.0 ± 8.9
21.3 ± 10.5
17.5 ± 10.2
15.9 ± 10.1
0.17 \0.0001
0.0002
SPK score
0.56 ± 0.53
0.52 ± 0.53
0.38 ± 0.51
0.10 ± 0.31
Meibum score
0.34 ± 0.54
0.30 ± 0.51
0.57 ± 0.63
0.21 ± 0.46
0.25
1.8 ± 1.5
1.5 ± 0.9
1.3 ± 1.5
0.7 ± 1.1
0.051
Meiboscore
The p values refer to the superficial punctate keratopathy (SPK) scores, meibum scores, meiboscores (Kruskal–Wallis test), BUTs, and Schirmer’s value (ANOVA) among the four groups. CL contact lens, AC allergic conjunctivitis, BUT tear film breakup time, SPK superficial punctate keratopathy Fig. 2a–h Representative meibography results. a An image with meibography and b a color photograph of a CL wearer with contact lens-related allergic conjunctivitis (CLAC). Meibomian gland distortion is observed. Meibomian gland distortion score: 2. Papilla formation and edematous conjunctiva are observed. c A meibography image and d a color photograph of a CL wearer without CLAC. A shortening of the meibomian glands is observed without any distortion. Neither papilla formation nor edematous conjunctiva are observed. e A meibography image and f a color photograph of a non-CL wearer with perennial allergic conjunctivitis (perennial AC). Meibomian gland distortion is observed. Meibomian gland distortion score: 2. Papilla formation is also observed. g A meibography image and h a color photograph of a normal volunteer. No meibomian gland distortion is observed. Neither papilla formation nor edematous conjunctiva are observed
Table 2 Mean (±standard deviation) meibomian gland distortion score in each group AC?
AC-
p value
CL wear -
0.75 ± 0.89
0.11 ± 0.31
\0.0001
CL wear ?
0.55 ± 0.82
0.091 ± 0.33
\0.0001
p value
0.27
0.61
CL contact lens, AC allergic conjunctivitis
Discussion Although AC is reported to be associated with tear film instability and dry eye [2, 3], morphological changes of the MG in patients with AC have not been investigated. In the present study, we examined MG morphology using noncontact meibography in patients with CLAC and perennial AC, and assessed the relations between observed morphological changes and eyelid and tear film parameters.
123
18
R. Arita et al.
Table 3 Correlations of meibomian gland distortion score with other parameters in contact lens wearers with or without allergic conjunctivitis Parameters
CL? R value
AC? group p value
BUT
-0.16
0.19
Schirmer’s
-0.16
0.21
CL? R value 0.080 -0.20
AC- group p value 0.49 0.78
SPK score
0.028
0.82
0.083
0.47
Meibum score
0.40
0.0017
0.14
0.24
0.030
0.81
0.27
0.019
-0.0080
0.53
-0.021
0.85
Meiboscore CL wear length
R value represents correlation coefficient obtained using Spearman correlation analysis BUT tear film breakup time, SPK superficial punctate keratopathy
In the present study, MG distortion was observed significantly more frequently in patients with CLAC than in CL wearers without CLAC. Moreover, MG distortion was more frequent in patients with perennial AC than in normal volunteers. There was no significant difference in the frequency of MG distortion between patients with perennial AC and the CLAC group or between CL wearers without CLAC and the normal volunteers. These findings suggest that AC, but not CL wear, is associated with MG distortion. Although the exact mechanism underlying the association between AC and MG distortion is unclear, inflammatory changes in the conjunctival tissue might induce pressure on the MG in the tarsus [4, 5], resulting in tear film instability, and leading to cornification and obstruction. Histologic examination of the distorted MG in patients with AC may be necessary to elucidate the relevant mechanism. Because patients with AC frequently rub their eyes, the rubbing could induce MG distortion. Furthermore, because distortion was confined to the upper eyelid and was not present in the lower eyelid, the rubbing quite possibly led to the distortion of the MG ducts of the upper eyelid [8]. There was a marginal difference in meiboscores among the four groups (p = 0.051). The meiboscores of the CL wearers both with and without CLAC tended to be higher than those of the non-CL wearers. These findings are in agreement with the findings of our previous study: that CL wear is associated with a decrease in the number of MGs [9]. On the other hand, as shown in the present study, CL wear is not associated with MG distortion. Therefore, CL wear is likely to decrease the number of meibomian glands, but it is not likely to induce meibomian gland distortion. The meibum score was significantly higher in the CL wearers with CLAC than in the CL wearers without CLAC. Moreover, in our recent study [8], the meibum score was significantly higher in perennial AC patients with MG distortion than in perennial AC patients without MG distortion. According to a previous report, distortion occurs in
123
the first stage of morphological changes of the MG [10]. Taken together, these findings indicate that MG distortion might decrease meibum expression during blinking. The abovementioned distortion was related to the meibum score, but not to the meiboscore. It is likely that the meiboscore reflects not the changes in shape but the lost area of the MG [6]. Although the BUT and superficial punctate keratopathy scores differed significantly among the four groups in the present study, these differences existed between the normal volunteer group and the other groups. Because CL wear causes tear film instability [11], it is reasonable that BUT was shorter in the CL wearers without CLAC than in the normal volunteers. The average BUT in the control group was short (5.3 s). People who typically have a shorter BUT, such as workers who frequently use a video display terminal, might have formed part of the control group [12]. It is also reasonable that the superficial punctate keratopathy score was lower in the normal volunteers than in the CL wearers without CLAC and the perennial AC group, because both CL wear and the presence of AC could induce superficial punctate keratopathy. In the present study, most of the MG distortions were observed in the upper eyelids. This finding is consistent with the fact that allergic inflammation such as GPC is observed in the upper tarsal conjunctiva more often than in other areas. Additionally, MG are much longer in the upper eyelids than in the lower eyelids, which may explain the greater incidence of MG distortion in the upper eyelids. There are two limitations of our study. One is that we did not observe the morphology of meibomian glands before either CL wear or AC. We did not examine whether those who had originally had duct distortions tended to suffer from AC. The other is that we did not examine the correlation between the MG duct distortions and either the quality or the quantity of meibum, as we graded the meibum score only in the center part of the upper eyelid, and graded the meibomian gland distortion score in the whole
Allergy and meibomian glands
upper eyelid. Therefore, we did not confirm whether a meibomian gland with duct distortion had any dysfunctions. In a future study, we plan to observe whether the MG distortion decreases with the treatment of allergic conjunctivitis. In conclusion, increased distortion and therefore allergic reaction, and not CL, appears to be responsible for the increase in MG distortion in patients with CLAC and with perennial allergic conjunctivitis.
References 1. Mathers WD, Billborough M. Meibomian gland function and giant papillary conjunctivitis. Am J Ophthalmol. 1992;114: 188–92. 2. Toda I, Shimazaki J, Tsubota K. Dry eye with only decreased tear break-up time is sometimes associated allergic conjunctivitis. Ophthalmology. 1995;102:302–9. 3. Suzuki S, Goto E, Dogru M, Asano-Kato N, Matsumoto Y, Hara Y, et al. Tear film lipid layer alteration in allergic conjunctivitis. Cornea. 2006;25:277–80.
19 4. Knop E, Knop N. Meibomian glands: part IV. Functional interactions in the pathogenesis of meibomian gland dysfunction (MGD). Ophthalmologe. 2009;106:980–7 (in German). 5. Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee for anatomy, physiology and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. 2011;52:1938–78. 6. 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. 7. Shimazaki J, Goto E, Ono M, Shimmura S, Tsubota K. Meibomian gland dysfunction in patients with Sjo¨gren syndrome. Ophthalmology. 1998;105:1485–8. 8. Arita R, Itoh K, Maeda S, Maeda K, Furuta A, Tomidokoro A, et al. Meibomian gland duct distortion in patients with perennial allergic conjunctivitis. Cornea. 2010;29:858–60. 9. Arita R, Itoh K, Inoue K, Kuchiba A, Yamaguchi T, Amano S. Contact lens wear is associated with decrease of meibomian glands. Ophthalmology. 2009;116:379–84. 10. Mathers WD, Shield WJ, Sachdev MS, Petroll WM, Jester JV. Meibomian gland dysfunction in chronic blepharitis. Cornea. 1991;10:277–85. 11. Nichols JJ, Sinnott LT. Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci. 2006;47:1319–28. 12. Tsubota K, Nakamori K. Dry eyes and video display terminals. N Eng J Med. 1993;328:584.
123
