- Email: [email protected]
Contact Lens Wear Is Associated with Decrease of Meibomian Glands
Contact Lens Wear Is Associated with Decrease of Meibomian Glands Reiko Arita, MD, PhD,1,2 Kouzo Itoh, MD, PhD,1 Kenji Inoue, MD, PhD,3 Aya Kuchiba, PhD,4 Takuhiro Yamaguchi, PhD,5 Shiro Amano, MD, PhD2 Purpose: Approximately 30% to 50% of contact lens (CL) wearers report dry eye symptoms. Meibomian gland dysfunction has been recognized as a possible cause of CL-related dry eye. This study investigated the influence of CL wear on the meibomian glands using a newly developed meibographic technique. Design: Cross-sectional observational case series. Participants: Contact lens wearers (n ⫽ 121; 47 men, 74 women; mean age⫾standard deviation, 31.8⫾8.0 years) and healthy volunteers (n ⫽ 137; 71 men, 66 women; mean age⫾standard deviation, 31.4⫾15.1 years). Methods: The following tests were performed: slit-lamp examinations of the eyelids, corneal and conjunctival staining using fluorescein, measurement of the tear film breakup time, evaluation of the meibomian glands using noncontact meibography, and measurement of tear production using the Schirmer I test. Partial or complete loss of the meibomian glands was scored for each eyelid using 4 grades (meiboscores): grade 0 (no loss of meibomian glands) through grade 3 (the area characterized by gland dropout was more than 66% of the total area containing the meibomian glands). The meiboscores for the upper and lower eyelids were summed for each subject. Main Outcome Measures: Score of meibomian gland changes (meiboscore), tear film breakup time, and Schirmer test value. Results: The meiboscore was significantly higher (P⬍0.0001) in CL wearers (mean, 1.72; 95% confidence interval, 1.47–1.96) than in the control group (mean, 0.96; 95% confidence interval, 0.73–1.19). The average meiboscore of CL wearers was similar to that of a 60- to 69-year-old age group from the normal population. A significant positive correlation was observed between the duration of CL wear and the meiboscore. Conclusions: Contact lens wear is associated with a decrease in the number of functional meibomian glands. This decrease is proportional to the duration of CL wear. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009;116:379 –384 © 2009 by the American Academy of Ophthalmology.
There are approximately 125 million contact lens (CL) wearers in the world.1 Although CLs are useful for correcting refractive errors without affecting the appearance of the wearer, CL use induces various complications, including infection, allergic conjunctivitis, corneal disorders, and dry eye. Among these complications, dry eye is particularly troubling because 30% to 50% of CL wearers report dry eye symptoms,2–5 and the discomfort associated with dry eye may lead to intolerance to CL wear. Several causative mechanisms have been proposed for dry eye in CL wearers including inflammation,6 – 8 increased evaporation and osmolarity of the tear film,9 –11 and dewetting of the CL surface.12,13 The meibomian glands are specialized sebaceous glands that secrete the oily layer of the tear film and prevent its evaporation; dysfunction of these glands leads to alterations in the lipid layer thickness and tear film instability. Therefore, abnormally functioning meibomian glands have been investigated as a possible cause for dry eye in CL wearers, although the potential association between CL wear and meibomian gland changes is controversial. Some studies have reported that obstruction of the meibomian gland orifices is observed more frequently in CL intolerant patients © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
than in CL wearers14 and is more prevalent in CL wearers than in nonwearers.15 However, another study found no significant difference between the meibomian gland lipids of CL wearers and nonwearers.16 Furthermore, Nichols and Sinnott17 examined various factors associated with selfreported CL-related dry eye and found no significant structural changes in the meibomian glands of CL wearers reporting dry eye compared with those of unaffected CL wearers. Thorough examinations for potential morphologic changes in the meibomian glands of CL wearers, however, have not been performed, because conventional meibography has a narrow observation area and is uncomfortable and painful for examinees.18 The authors have developed a noncontact, patient-friendly meibographic technique using an infrared filter and an infrared charge-coupled device (CCD) camera, which enables performance of quick and thorough examinations for morphologic changes in meibomian glands throughout the eye.19 The purpose of this study was to compare changes observed in the meibomian glands of CL wearers and nonwearers and to analyze the relationship between these changes and other factors including CL type, duration of CL wear, tear film function, and ocular surface epitheliopathy. ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2008.10.012
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Figure 1. Representative results of meibography in (A, B) contact lens (CL) wearers and (C) a control subject. A, In a 23-year-old man who had used rigid gas-permeable CLs for 8 years, most meibomian glands in both the upper and lower eyelids were shortened. The areas in which meibomian glands were absent are encircled with dotted white lines. The shortening of the meibomian glands began not from the orifice side but from the distal side. B, In a 28-year-old woman who had used hydrogel CLs for 12 years, shortening and dropout of meibomian glands were observed in both the upper and lower eyelids. The areas where meibomian glands were absent are encircled with dotted white lines.
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Arita et al 䡠 Contact Lens Association with Decreased Meibomian Glands
Figure 1. (Continued.) C, A 29-year-old nonwearer. Shortening or dropout of meibomian glands was not observed.
Patients and Methods The study examined 121 eyes from 121 CL wearers (47 males and 74 females) and 137 eyes from 137 nonwearers (71 males and 66 females) as control samples. Both CL wearers and the control subjects were consecutive volunteer cases. Written informed consent was obtained from each subject before the examination. When subjects were younger than 20 years old, written informed consent was obtained from their parents. This study was approved by the institutional review board of the Inouye Eye Hospital and adhered to the tenets of the Declaration of Helsinki. The mean ages⫾standard deviations of the CL wearers and the control group were 31.8⫾8.0 years and 31.4⫾15.1 years, respectively. The entry criteria for CL wearers included volunteers who had been wearing CLs for at least 1 year and had no evidence of ocular diseases other than those associated with CL-related changes, such as superficial punctuate keratopathy (SPK) and giant papillary conjunctivitis. Data used in this study were obtained from the right eye of each subject. When the right eye was excluded from the study, data from the left eye were used. The entry criteria for the control group included volunteers who had not worn CLs and had no ocular diseases. After the CL was removed, the following examinations were performed in sequence: manifest refraction, slit-lamp examination of the eyelids, SPK staining observed with a blue-free filter after
instillation of fluorescein, measurement of the tear film breakup time (BUT), grading of meibomian gland dropout, and measurement of tear production using the Schirmer test without topical anesthetic. Lid margin abnormalities were scored from 0 to 4 based on the presence of 4 criteria: irregular lid margin, vascular engorgement, plugging of meibomian gland orifices, and shift of the mucocutaneous junction. An absolute scale (score 0 or 1) was chosen for each of the 4 criteria, and the severity in each criterion was not taken into consideration. The examiners were masked to which subjects were CL wearers and which were control subjects. The SPK staining was graded as 0 (no staining), 1 (mild staining with a few disseminated stains and limited to less than one third of the cornea), 2 (moderate staining with severity between 1 and 3), or 3 (severe staining with confluent stains and occupying half or more of the cornea).20 The tear film BUT was measured 3 consecutive times after the instillation of fluorescein. Upper and lower eyelids were turned over and the meibomian glands were observed with the novel noncontact infrared meibographic method. Partial or complete loss of the meibomian glands was scored using the following grades (meiboscores) for each eyelid: grade 0 (no loss of meibomian glands), grade 1 (the affected area was less than 33% of the total area occupied by the meibomian glands), grade 2 (the affected area was between 33% and 66% of the total area occupied by the meibomian glands), grade 3 (the affected area was more
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Ophthalmology Volume 116, Number 3, March 2009 Table 1. Mean Meiboscores in Contact Lens Wearers and Nonwearers Mean Meiboscore (95% Confidence Interval)
Total Upper eyelid Lower eyelid
Contact Lens Wearers
Nonwearers
P Value
1.72 (1.47–1.96) 0.86 (0.71–1.01) 0.87 (0.68–1.05)
0.96 (0.73–1.19) 0.32 (0.24–0.40) 0.62 (0.48–0.76)
⬍0.0001 ⬍0.0001 0.036
than 66% of the total area occupied by the meibomian glands).19 Meiboscores for upper and lower eyelids were summed for each eye.
Statistical Analysis The average scores for SPK and lid margin abnormality, the average BUTs, and Schirmer values in CL wearers and nonwearers were compared using the Mann–Whitney U test. The meiboscore differences between CL-wearers and nonwearers and between rigid gas permeable (RGP) lens wearers and hydrogel lens wearers were estimated using an analysis of covariance, adjusted for age and gender because a previous study found that age and gender affect meibomian gland loss.19 The meiboscores from the upper and lower eyelids were compared using the generalized estimating equations method to account for intrasubject correlation of the meiboscores. In CL wearers, multiple regression analyses, including such independent variables as age, gender, and each predictor parameter, were performed to examine the relationship between meiboscores and each predictor variable.
Results Factors Related to Contact Lens Wear Among the CL wearers, 39 subjects used RGP lenses and 82 used hydrogel lenses (15 conventional hydrogel lenses and 67 disposable hydrogel lenses). Fourteen individuals had used both RGP lenses and hydrogel lenses at some point. Because each of these 14 subjects had used their current type of lenses for more than 3 years, they were deemed to be either RGP lens wearers or hydrogel lens wearers depending on the type of lenses they were using at the time of the examinations. The average duration of CL wear was 12.3⫾7.2 years (range, 1– 40 years) and the average spherical equivalent was ⫺5.1⫾2.7 diopters.
Comparison of Tear Film-Related Factors in Contact Lens Wearers and the Control Group The mean SPK scores⫾standard deviations in CL wearers and nonwearers were 0.58⫾0.59 and 0.13⫾0.36, respectively (P⬍0.0001). The mean scores⫾standard deviations for the lid margin in CL wearers and nonwearers were 0.40⫾0.50 and 0.24⫾0.53, respectively (P ⫽ 0.036). The mean⫾standard deviation BUTs in CL wearers and nonwearers were 4.8⫾2.6 s and 6.7⫾3.1 seconds, respectively (P⬍0.0001). The mean⫾standard deviation Schirmer values in CL wearers and nonwearers were 20.4⫾10.1 mm and 20.2⫾11.3 mm, respectively (P ⫽ 0.953).
similarly shortened clusters of meibomian glands. The shortening of the meibomian glands in CL wearers occurred not at the side with the orifices, but instead was observed on the distal side; the length of the affected meibomian glands was less than half that observed for normal glands. These patterns of meibomian gland changes were rare in the control samples. Analyses of covariance for the meiboscores with adjustments for age and gender are shown in Table 1. The average upper eyelid, lower eyelid, and total (upper eyelid plus lower eyelid) meiboscores in CL wearers were significantly higher than those in nonwearers. The average differences between the meiboscores of CL wearers and nonwearers in the upper and lower eyelids were 0.54 (95% confidence interval, 0.37– 0.71; P⬍0.0001) and 0.25 (95% confidence interval, 0.02 to 0.48; P ⫽ 0.036), respectively. This suggests that the wearing of CLs produces different effects on the upper and lower eyelids (P ⫽ 0.012, test for interaction).
Contact Lens Type and the Affected Meibomian Gland Area The results of the analyses of covariance for meiboscores in RGP lens and hydrogel lens wearers, adjusted for age and gender, are shown in Table 2. There was no significant difference in the average meiboscores from RGP lens wearers and hydrogel lens wearers.
Relationship between the Meiboscore and Other Factors in Contact Lens Wearers and Nonwearers Table 3 displays the results from multiple regression analyses for each variable. The duration of CL wear was the only variable that was significantly associated with the meiboscores. The regression coefficient between meiboscores and duration of CL wear was 0.066.
Discussion In this study, thorough examinations of meibomian glands in CL wearers and control subjects were performed using a novel noncontact meibographic technique, and the results showed that CL wearers have a significantly greater degree of meibomian gland loss than nonwearers. This suggests that the meibomian gland loss is one of the mechanisms underlying CL-related dry eye. A recent study examined parameters related to the tear film, CL wear, clinical presentation, including meibomian gland structure, and patient characteristics to determine their relationship with self-reported CLrelated dry eye; multivariate modeling showed that several factors were associated with dry eye status, including female Table 2. Average Meiboscores in Rigid Gas Permeable Lens Wearers and Hydrogel Lens Wearers Mean Meiboscore (95% Confidence Interval)
Comparison of the Meibomian Gland Changes Observed in Contact Lens Wearers and the Control Group Figure 1 shows representative cases from the CL wearers and the normal control group. Contact lens wearers commonly showed
382
Total Upper eyelid Lower eyelid
Rigid Gas Permeable Lens Wearers
Hydrogel Lens Wearers
P Value
2.04 (1.54–2.55) 0.98 (0.71–1.25) 1.06 (0.69–1.43)
1.52 (1.17–1.86) 0.77 (0.60–0.94) 0.75 (0.54–0.95)
0.092 0.193 0.145
Arita et al 䡠 Contact Lens Association with Decreased Meibomian Glands Table 3. Results from Multiple Regression Analyses for Meiboscores in Contact Lens Wearers Variables Duration of contact lens wear (yrs) Spherical component of refraction (D) Cylindrical component of refraction (D) Lid margin score Superficial punctuate keratopathy score Tear breakup time (seconds) Schirmer value (mm)
Coefficient
Standard Error
P Value
0.066
0.028
0.020
0.064
0.054
0.240
0.177
0.231
0.446
⫺0.071 0.440
0.285 0.238
0.802 0.067
⫺0.084
0.055
0.130
⫺0.007
0.014
0.602
D ⫽ diopters.
gender, rapid prelens tear film thinning, and increased tear film osmolarity.17 The data did not show that the extent of meibomian gland dropout was related to dry eye status in CL wearers. The study, however, only examined the meibomian glands in the central area of the lower eyelid, whereas this study examined the meibomian glands throughout the upper and lower eyelids. These results show that the effects of CL wear on meibomian glands are significantly greater in the upper eyelid than in the lower eyelid. Thus, meibomian gland changes in the central area of lower eyelid do not necessarily represent the full extent of changes in these glands, indicating that these results are likely to be more reliable than those previously published.17 Among the examined parameters, the duration of CL wear was the only variable that was significantly associated with the meiboscore. In the previous study using the same meibographic method, the authors found that aging increased the severity of meibomian gland changes in normal individuals.19 Thus, both aging and CL wear produce similar dropout effects on the meibomian glands. Moreover, the current study showed that CL wearers have a significantly higher degree of meibomian gland loss than nonwearers. Taken together, these results suggest that CL wear accelerates age-related changes in the meibomian glands. In fact, CL wearers in this study (mean age, 31.8 years) had an average meiboscore of 1.72, which is similar to that observed in a 60- to 69-year-old age group from the normal population.19 The results of analyses of covariance for meiboscores in RGP lens and hydrogel lens wearers, adjusted for age and gender, showed no significant difference in the average meiboscores. This result suggests that lens materials do not play a significant role in CL-related dry eye. Two hypotheses have been proposed as causative mechanisms for meibomian gland loss in CL wearers. Ong and Larke15 suggested that mechanical trauma from the CLs causes duct blockage in the meibomian glands. However, Henriquez and Korb14 and Korb and Henriquez21 suggested that meibomian gland dysfunction is a result of the aggregation of desquamated epithelial cells at the orifices of the glands. In most of the CL wearers with meibomian gland changes, the clusters of meibomian glands were similarly shortened. Moreover, the
shortening of the meibomian glands in CL wearers began from the distal side. These results suggest that chronic irritation of meibomian glands by CLs through conjunctiva is a major causative mechanism for meibomian gland changes in CL wearers. This hypothesis seems to be consistent with the observation that loss of meibomian glands depends on the duration of CL wear but not on the CL materials. The average difference between the meiboscores of CL wearers and nonwearers was significantly greater for the upper eyelid than for the lower eyelid, suggesting that the effects of CL wear on the meibomian glands are of greater concern in the upper eyelid. Although CLs attach to both the upper and lower eyelids, the upper eyelid may experience more irritation because it makes larger movements during blinking. The greater CL effect on the upper eyelid also supports the hypothesis that chronic CL-mediated irritation of the meibomian glands through conjunctiva is a major contributor to meibomian gland changes in CL wearers. In this study, the tear film BUT in CL wearers was shorter than that in nonwearers, and the SPK score in CL wearers was higher than that in nonwearers. However, the Schirmer values in CL wearers and nonwearers were similar. These results indicate that dry eye resulting from increased evaporation of the tear film is more prevalent in CL wearers than in nonwearers, which agrees with the results of previous studies.9,17 In conclusion, CL wear is associated with a decrease in the number of functional meibomian glands; this decrease is proportional to the duration of CL wear and may contribute to dry eye in CL wearers.
References 1. Barr JT. 2004 Annual Report. Contact Lens Spectrum January 2005. Available at: http://www.clspectrum.com/article.aspx? article⫽12733. Accessed October 8, 2008. 2. Doughty MJ, Fonn D, Richter D, et al. A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada. Optom Vis Sci 1997;74:624 –31. 3. Nichols JJ, Mitchell GL, Nichols KK, et al. The performance of the contact lens dry eye questionnaire as a screening survey for contact lens-related dry eye. Cornea 2002;21:469 –75. 4. Begley CG, Chalmers RL, Mitchell GL, et al. Characterization of ocular surface symptoms from optometric practices in North America. Cornea 2001;20:610 – 8. 5. Begley CG, Caffery B, Nichols KK, Chalmers R. Responses of contact lens wearers to a dry eye survey. Optom Vis Sci 2000;77:40 – 6. 6. Schultz CL, Kunert KS. Interleukin-6 levels in tears of contact lens wearers. J Interferon Cytokine Res 2000;20:309 –10. 7. Pisella PJ, Malet F, Lejeune S, et al. Ocular surface changes induced by contact lens wear. Cornea 2001;20:820 –5. 8. Willcox MD, Lan J. Secretory immunoglobulin A in tears: functions and changes during contact lens wear. Clin Exp Optom 1999;82:1–3. 9. Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21:221–32. 10. Mackie IA. Contact lenses in dry eyes. Trans Ophthalmol Soc U K 1985;104:477– 83.
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Ophthalmology Volume 116, Number 3, March 2009 11. Gilbard JP, Gray KL, Rossi SR. A proposed mechanism for increased tear-film osmolarity in contact lens wearers. Am J Ophthalmol 1986;102:505–7. 12. Holly F, Refojo MF. Wettability of hydrogels. I. Poly (2hydroxyethyl methacrylate). J Biomed Mater Res 1975;9:315–26. 13. Hatfield RO, Jordan DR, Bennett ES, et al. Initial comfort and surface wettability: a comparison between different contact lens materials. J Am Optom Assoc 1993;64:271–3. 14. Henriquez AS, Korb DR. Meibomian glands and contact lens wear. Br J Ophthalmol 1981;65:108 –11. 15. Ong BL, Larke JR. Meibomian gland dysfunction: some clinical, biochemical and physical observations. Ophthalmic Physiol Opt 1990;10:144 – 8. 16. Ong BL. Relation between contact lens wear and meibomian gland dysfunction. Optom Vis Sci 1996;73:208 –10.
17. Nichols JJ, Sinnott LT. Tear film, contact lens, and patientrelated factors associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci 2006;47:1319 –28. 18. Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1:107–26. 19. 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. 20. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 2003;110:1096 –101. 21. Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc 1980;51: 243–51.
Footnotes and Financial Disclosures Originally received: July 31, 2008. Final revision: August 29, 2008. Accepted: October 9, 2008. Available online: January 22, 2009. 1
5
Manuscript no. 2008-921.
Itoh Clinic, Saitama, Japan.
2
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
3
Inouye Eye Hospital, Tokyo, Japan.
4
Genetics Division, Research Institute, National Cancer Center, Tokyo, Japan.
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Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo Hospital, Tokyo, Japan. Financial Disclosure(s): The author(s) have made the following disclosure(s): Drs Arita and Amano are applying for a patent for the meibography system used in this study. Correspondence: Shiro Amano, MD, PhD, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail: [email protected]. Reiko Arita, MD, PhD, 626-11 Minaminakano, Minuma-ku, Saitama city, Saitama, 337-0042, Japan. Email: [email protected].
There are approximately 125 million contact lens (CL) wearers in the world.1 Although CLs are useful for correcting refractive errors without affecting the appearance of the wearer, CL use induces various complications, including infection, allergic conjunctivitis, corneal disorders, and dry eye. Among these complications, dry eye is particularly troubling because 30% to 50% of CL wearers report dry eye symptoms,2–5 and the discomfort associated with dry eye may lead to intolerance to CL wear. Several causative mechanisms have been proposed for dry eye in CL wearers including inflammation,6 – 8 increased evaporation and osmolarity of the tear film,9 –11 and dewetting of the CL surface.12,13 The meibomian glands are specialized sebaceous glands that secrete the oily layer of the tear film and prevent its evaporation; dysfunction of these glands leads to alterations in the lipid layer thickness and tear film instability. Therefore, abnormally functioning meibomian glands have been investigated as a possible cause for dry eye in CL wearers, although the potential association between CL wear and meibomian gland changes is controversial. Some studies have reported that obstruction of the meibomian gland orifices is observed more frequently in CL intolerant patients © 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
than in CL wearers14 and is more prevalent in CL wearers than in nonwearers.15 However, another study found no significant difference between the meibomian gland lipids of CL wearers and nonwearers.16 Furthermore, Nichols and Sinnott17 examined various factors associated with selfreported CL-related dry eye and found no significant structural changes in the meibomian glands of CL wearers reporting dry eye compared with those of unaffected CL wearers. Thorough examinations for potential morphologic changes in the meibomian glands of CL wearers, however, have not been performed, because conventional meibography has a narrow observation area and is uncomfortable and painful for examinees.18 The authors have developed a noncontact, patient-friendly meibographic technique using an infrared filter and an infrared charge-coupled device (CCD) camera, which enables performance of quick and thorough examinations for morphologic changes in meibomian glands throughout the eye.19 The purpose of this study was to compare changes observed in the meibomian glands of CL wearers and nonwearers and to analyze the relationship between these changes and other factors including CL type, duration of CL wear, tear film function, and ocular surface epitheliopathy. ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2008.10.012
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Ophthalmology Volume 116, Number 3, March 2009
Figure 1. Representative results of meibography in (A, B) contact lens (CL) wearers and (C) a control subject. A, In a 23-year-old man who had used rigid gas-permeable CLs for 8 years, most meibomian glands in both the upper and lower eyelids were shortened. The areas in which meibomian glands were absent are encircled with dotted white lines. The shortening of the meibomian glands began not from the orifice side but from the distal side. B, In a 28-year-old woman who had used hydrogel CLs for 12 years, shortening and dropout of meibomian glands were observed in both the upper and lower eyelids. The areas where meibomian glands were absent are encircled with dotted white lines.
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Arita et al 䡠 Contact Lens Association with Decreased Meibomian Glands
Figure 1. (Continued.) C, A 29-year-old nonwearer. Shortening or dropout of meibomian glands was not observed.
Patients and Methods The study examined 121 eyes from 121 CL wearers (47 males and 74 females) and 137 eyes from 137 nonwearers (71 males and 66 females) as control samples. Both CL wearers and the control subjects were consecutive volunteer cases. Written informed consent was obtained from each subject before the examination. When subjects were younger than 20 years old, written informed consent was obtained from their parents. This study was approved by the institutional review board of the Inouye Eye Hospital and adhered to the tenets of the Declaration of Helsinki. The mean ages⫾standard deviations of the CL wearers and the control group were 31.8⫾8.0 years and 31.4⫾15.1 years, respectively. The entry criteria for CL wearers included volunteers who had been wearing CLs for at least 1 year and had no evidence of ocular diseases other than those associated with CL-related changes, such as superficial punctuate keratopathy (SPK) and giant papillary conjunctivitis. Data used in this study were obtained from the right eye of each subject. When the right eye was excluded from the study, data from the left eye were used. The entry criteria for the control group included volunteers who had not worn CLs and had no ocular diseases. After the CL was removed, the following examinations were performed in sequence: manifest refraction, slit-lamp examination of the eyelids, SPK staining observed with a blue-free filter after
instillation of fluorescein, measurement of the tear film breakup time (BUT), grading of meibomian gland dropout, and measurement of tear production using the Schirmer test without topical anesthetic. Lid margin abnormalities were scored from 0 to 4 based on the presence of 4 criteria: irregular lid margin, vascular engorgement, plugging of meibomian gland orifices, and shift of the mucocutaneous junction. An absolute scale (score 0 or 1) was chosen for each of the 4 criteria, and the severity in each criterion was not taken into consideration. The examiners were masked to which subjects were CL wearers and which were control subjects. The SPK staining was graded as 0 (no staining), 1 (mild staining with a few disseminated stains and limited to less than one third of the cornea), 2 (moderate staining with severity between 1 and 3), or 3 (severe staining with confluent stains and occupying half or more of the cornea).20 The tear film BUT was measured 3 consecutive times after the instillation of fluorescein. Upper and lower eyelids were turned over and the meibomian glands were observed with the novel noncontact infrared meibographic method. Partial or complete loss of the meibomian glands was scored using the following grades (meiboscores) for each eyelid: grade 0 (no loss of meibomian glands), grade 1 (the affected area was less than 33% of the total area occupied by the meibomian glands), grade 2 (the affected area was between 33% and 66% of the total area occupied by the meibomian glands), grade 3 (the affected area was more
381
Ophthalmology Volume 116, Number 3, March 2009 Table 1. Mean Meiboscores in Contact Lens Wearers and Nonwearers Mean Meiboscore (95% Confidence Interval)
Total Upper eyelid Lower eyelid
Contact Lens Wearers
Nonwearers
P Value
1.72 (1.47–1.96) 0.86 (0.71–1.01) 0.87 (0.68–1.05)
0.96 (0.73–1.19) 0.32 (0.24–0.40) 0.62 (0.48–0.76)
⬍0.0001 ⬍0.0001 0.036
than 66% of the total area occupied by the meibomian glands).19 Meiboscores for upper and lower eyelids were summed for each eye.
Statistical Analysis The average scores for SPK and lid margin abnormality, the average BUTs, and Schirmer values in CL wearers and nonwearers were compared using the Mann–Whitney U test. The meiboscore differences between CL-wearers and nonwearers and between rigid gas permeable (RGP) lens wearers and hydrogel lens wearers were estimated using an analysis of covariance, adjusted for age and gender because a previous study found that age and gender affect meibomian gland loss.19 The meiboscores from the upper and lower eyelids were compared using the generalized estimating equations method to account for intrasubject correlation of the meiboscores. In CL wearers, multiple regression analyses, including such independent variables as age, gender, and each predictor parameter, were performed to examine the relationship between meiboscores and each predictor variable.
Results Factors Related to Contact Lens Wear Among the CL wearers, 39 subjects used RGP lenses and 82 used hydrogel lenses (15 conventional hydrogel lenses and 67 disposable hydrogel lenses). Fourteen individuals had used both RGP lenses and hydrogel lenses at some point. Because each of these 14 subjects had used their current type of lenses for more than 3 years, they were deemed to be either RGP lens wearers or hydrogel lens wearers depending on the type of lenses they were using at the time of the examinations. The average duration of CL wear was 12.3⫾7.2 years (range, 1– 40 years) and the average spherical equivalent was ⫺5.1⫾2.7 diopters.
Comparison of Tear Film-Related Factors in Contact Lens Wearers and the Control Group The mean SPK scores⫾standard deviations in CL wearers and nonwearers were 0.58⫾0.59 and 0.13⫾0.36, respectively (P⬍0.0001). The mean scores⫾standard deviations for the lid margin in CL wearers and nonwearers were 0.40⫾0.50 and 0.24⫾0.53, respectively (P ⫽ 0.036). The mean⫾standard deviation BUTs in CL wearers and nonwearers were 4.8⫾2.6 s and 6.7⫾3.1 seconds, respectively (P⬍0.0001). The mean⫾standard deviation Schirmer values in CL wearers and nonwearers were 20.4⫾10.1 mm and 20.2⫾11.3 mm, respectively (P ⫽ 0.953).
similarly shortened clusters of meibomian glands. The shortening of the meibomian glands in CL wearers occurred not at the side with the orifices, but instead was observed on the distal side; the length of the affected meibomian glands was less than half that observed for normal glands. These patterns of meibomian gland changes were rare in the control samples. Analyses of covariance for the meiboscores with adjustments for age and gender are shown in Table 1. The average upper eyelid, lower eyelid, and total (upper eyelid plus lower eyelid) meiboscores in CL wearers were significantly higher than those in nonwearers. The average differences between the meiboscores of CL wearers and nonwearers in the upper and lower eyelids were 0.54 (95% confidence interval, 0.37– 0.71; P⬍0.0001) and 0.25 (95% confidence interval, 0.02 to 0.48; P ⫽ 0.036), respectively. This suggests that the wearing of CLs produces different effects on the upper and lower eyelids (P ⫽ 0.012, test for interaction).
Contact Lens Type and the Affected Meibomian Gland Area The results of the analyses of covariance for meiboscores in RGP lens and hydrogel lens wearers, adjusted for age and gender, are shown in Table 2. There was no significant difference in the average meiboscores from RGP lens wearers and hydrogel lens wearers.
Relationship between the Meiboscore and Other Factors in Contact Lens Wearers and Nonwearers Table 3 displays the results from multiple regression analyses for each variable. The duration of CL wear was the only variable that was significantly associated with the meiboscores. The regression coefficient between meiboscores and duration of CL wear was 0.066.
Discussion In this study, thorough examinations of meibomian glands in CL wearers and control subjects were performed using a novel noncontact meibographic technique, and the results showed that CL wearers have a significantly greater degree of meibomian gland loss than nonwearers. This suggests that the meibomian gland loss is one of the mechanisms underlying CL-related dry eye. A recent study examined parameters related to the tear film, CL wear, clinical presentation, including meibomian gland structure, and patient characteristics to determine their relationship with self-reported CLrelated dry eye; multivariate modeling showed that several factors were associated with dry eye status, including female Table 2. Average Meiboscores in Rigid Gas Permeable Lens Wearers and Hydrogel Lens Wearers Mean Meiboscore (95% Confidence Interval)
Comparison of the Meibomian Gland Changes Observed in Contact Lens Wearers and the Control Group Figure 1 shows representative cases from the CL wearers and the normal control group. Contact lens wearers commonly showed
382
Total Upper eyelid Lower eyelid
Rigid Gas Permeable Lens Wearers
Hydrogel Lens Wearers
P Value
2.04 (1.54–2.55) 0.98 (0.71–1.25) 1.06 (0.69–1.43)
1.52 (1.17–1.86) 0.77 (0.60–0.94) 0.75 (0.54–0.95)
0.092 0.193 0.145
Arita et al 䡠 Contact Lens Association with Decreased Meibomian Glands Table 3. Results from Multiple Regression Analyses for Meiboscores in Contact Lens Wearers Variables Duration of contact lens wear (yrs) Spherical component of refraction (D) Cylindrical component of refraction (D) Lid margin score Superficial punctuate keratopathy score Tear breakup time (seconds) Schirmer value (mm)
Coefficient
Standard Error
P Value
0.066
0.028
0.020
0.064
0.054
0.240
0.177
0.231
0.446
⫺0.071 0.440
0.285 0.238
0.802 0.067
⫺0.084
0.055
0.130
⫺0.007
0.014
0.602
D ⫽ diopters.
gender, rapid prelens tear film thinning, and increased tear film osmolarity.17 The data did not show that the extent of meibomian gland dropout was related to dry eye status in CL wearers. The study, however, only examined the meibomian glands in the central area of the lower eyelid, whereas this study examined the meibomian glands throughout the upper and lower eyelids. These results show that the effects of CL wear on meibomian glands are significantly greater in the upper eyelid than in the lower eyelid. Thus, meibomian gland changes in the central area of lower eyelid do not necessarily represent the full extent of changes in these glands, indicating that these results are likely to be more reliable than those previously published.17 Among the examined parameters, the duration of CL wear was the only variable that was significantly associated with the meiboscore. In the previous study using the same meibographic method, the authors found that aging increased the severity of meibomian gland changes in normal individuals.19 Thus, both aging and CL wear produce similar dropout effects on the meibomian glands. Moreover, the current study showed that CL wearers have a significantly higher degree of meibomian gland loss than nonwearers. Taken together, these results suggest that CL wear accelerates age-related changes in the meibomian glands. In fact, CL wearers in this study (mean age, 31.8 years) had an average meiboscore of 1.72, which is similar to that observed in a 60- to 69-year-old age group from the normal population.19 The results of analyses of covariance for meiboscores in RGP lens and hydrogel lens wearers, adjusted for age and gender, showed no significant difference in the average meiboscores. This result suggests that lens materials do not play a significant role in CL-related dry eye. Two hypotheses have been proposed as causative mechanisms for meibomian gland loss in CL wearers. Ong and Larke15 suggested that mechanical trauma from the CLs causes duct blockage in the meibomian glands. However, Henriquez and Korb14 and Korb and Henriquez21 suggested that meibomian gland dysfunction is a result of the aggregation of desquamated epithelial cells at the orifices of the glands. In most of the CL wearers with meibomian gland changes, the clusters of meibomian glands were similarly shortened. Moreover, the
shortening of the meibomian glands in CL wearers began from the distal side. These results suggest that chronic irritation of meibomian glands by CLs through conjunctiva is a major causative mechanism for meibomian gland changes in CL wearers. This hypothesis seems to be consistent with the observation that loss of meibomian glands depends on the duration of CL wear but not on the CL materials. The average difference between the meiboscores of CL wearers and nonwearers was significantly greater for the upper eyelid than for the lower eyelid, suggesting that the effects of CL wear on the meibomian glands are of greater concern in the upper eyelid. Although CLs attach to both the upper and lower eyelids, the upper eyelid may experience more irritation because it makes larger movements during blinking. The greater CL effect on the upper eyelid also supports the hypothesis that chronic CL-mediated irritation of the meibomian glands through conjunctiva is a major contributor to meibomian gland changes in CL wearers. In this study, the tear film BUT in CL wearers was shorter than that in nonwearers, and the SPK score in CL wearers was higher than that in nonwearers. However, the Schirmer values in CL wearers and nonwearers were similar. These results indicate that dry eye resulting from increased evaporation of the tear film is more prevalent in CL wearers than in nonwearers, which agrees with the results of previous studies.9,17 In conclusion, CL wear is associated with a decrease in the number of functional meibomian glands; this decrease is proportional to the duration of CL wear and may contribute to dry eye in CL wearers.
References 1. Barr JT. 2004 Annual Report. Contact Lens Spectrum January 2005. Available at: http://www.clspectrum.com/article.aspx? article⫽12733. Accessed October 8, 2008. 2. Doughty MJ, Fonn D, Richter D, et al. A patient questionnaire approach to estimating the prevalence of dry eye symptoms in patients presenting to optometric practices across Canada. Optom Vis Sci 1997;74:624 –31. 3. Nichols JJ, Mitchell GL, Nichols KK, et al. The performance of the contact lens dry eye questionnaire as a screening survey for contact lens-related dry eye. Cornea 2002;21:469 –75. 4. Begley CG, Chalmers RL, Mitchell GL, et al. Characterization of ocular surface symptoms from optometric practices in North America. Cornea 2001;20:610 – 8. 5. Begley CG, Caffery B, Nichols KK, Chalmers R. Responses of contact lens wearers to a dry eye survey. Optom Vis Sci 2000;77:40 – 6. 6. Schultz CL, Kunert KS. Interleukin-6 levels in tears of contact lens wearers. J Interferon Cytokine Res 2000;20:309 –10. 7. Pisella PJ, Malet F, Lejeune S, et al. Ocular surface changes induced by contact lens wear. Cornea 2001;20:820 –5. 8. Willcox MD, Lan J. Secretory immunoglobulin A in tears: functions and changes during contact lens wear. Clin Exp Optom 1999;82:1–3. 9. Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21:221–32. 10. Mackie IA. Contact lenses in dry eyes. Trans Ophthalmol Soc U K 1985;104:477– 83.
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Ophthalmology Volume 116, Number 3, March 2009 11. Gilbard JP, Gray KL, Rossi SR. A proposed mechanism for increased tear-film osmolarity in contact lens wearers. Am J Ophthalmol 1986;102:505–7. 12. Holly F, Refojo MF. Wettability of hydrogels. I. Poly (2hydroxyethyl methacrylate). J Biomed Mater Res 1975;9:315–26. 13. Hatfield RO, Jordan DR, Bennett ES, et al. Initial comfort and surface wettability: a comparison between different contact lens materials. J Am Optom Assoc 1993;64:271–3. 14. Henriquez AS, Korb DR. Meibomian glands and contact lens wear. Br J Ophthalmol 1981;65:108 –11. 15. Ong BL, Larke JR. Meibomian gland dysfunction: some clinical, biochemical and physical observations. Ophthalmic Physiol Opt 1990;10:144 – 8. 16. Ong BL. Relation between contact lens wear and meibomian gland dysfunction. Optom Vis Sci 1996;73:208 –10.
17. Nichols JJ, Sinnott LT. Tear film, contact lens, and patientrelated factors associated with contact lens-related dry eye. Invest Ophthalmol Vis Sci 2006;47:1319 –28. 18. Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1:107–26. 19. 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. 20. Lin PY, Tsai SY, Cheng CY, et al. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 2003;110:1096 –101. 21. Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc 1980;51: 243–51.
Footnotes and Financial Disclosures Originally received: July 31, 2008. Final revision: August 29, 2008. Accepted: October 9, 2008. Available online: January 22, 2009. 1
5
Manuscript no. 2008-921.
Itoh Clinic, Saitama, Japan.
2
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
3
Inouye Eye Hospital, Tokyo, Japan.
4
Genetics Division, Research Institute, National Cancer Center, Tokyo, Japan.
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Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo Hospital, Tokyo, Japan. Financial Disclosure(s): The author(s) have made the following disclosure(s): Drs Arita and Amano are applying for a patent for the meibography system used in this study. Correspondence: Shiro Amano, MD, PhD, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail: [email protected]. Reiko Arita, MD, PhD, 626-11 Minaminakano, Minuma-ku, Saitama city, Saitama, 337-0042, Japan. Email: [email protected].