Shiraishi, Atsushi M.D., Ph.D.; Yamaguchi, Masahiko M.D., Ph.D.; Ohashi, Yuichi M.D., Ph.D.
Lid-wiper epitheliopathy (LWE) is defined as an epitheliopathy of a portion of the marginal conjunctiva of the upper eyelid.1 Korb et al.1 reported that the presence of LWE was correlated with dry eye symptoms in contact lens (CL) wearers. They studied LWE patients with or without dry eye intensively and showed that LWE occurs more frequently in patients with dry eye symptoms than without dry eyes.2,3 In their recent report, they showed that the prevalence of LWE was higher in dry eye disease and suggested that LWE may be a diagnostic sign of dry eye disease.2 However, their results also showed that LWE occurs in subjects without the conventional dry eye signs such as the Schirmer test and tear break-up time (BUT).3 Although LWE may be caused by an alteration of the lubrication between the epithelium of the lid wiper and the ocular surface, the cause remains elusive.
It has been reported that the epithelial alterations occur only in upper eyelid as LWE, and Doughty et al.4 demonstrated a similar staining with lissamine green (LG) at the lower eyelid margin. We also found a similar epitheliopathy at the lower eyelid margin.5 Knop et al.6,7 described the anatomical changes of the lid margins and showed that the characteristics of the lid-wiper region were similar for the upper and lower eyelids. Thus, the LWE-like staining in the lower eyelid margin may have the same or similar pathological basis as the LWE of the upper eyelid margin. However, the mechanism causing the LWE for either eyelid has not been definitively determined.
Thus, the purpose of this study was to determine the prevalence and degree of LWE (upper-LWE) and LWE-like staining in the lower eyelid (lower-LWE) in a large number of CL wearers and non-wearers. We also determined if there were significant correlations between the prevalence and degree of LWEs and the age, sex, corneal and conjunctival staining, and CL wear.
MATERIALS AND METHODS
The total number of the subjects was 508, including 229 non-CL wearers, 137 soft contact lens (SCL) wearers, and 71 rigid gas permeable contact lens (RGPCL) wearers. All were patients of the outpatient clinic of the Department of Ophthalmology, Ehime University Hospital. The presence of LWEs was determined in all patients who visited two experienced ophthalmologists (A.S. and M.Y.) on the same day. Subjects with acute inflammatory ocular surface disorders, eyelid closure failure, deformed eyelids, conjunctival concretions, abnormal blinking disorders, or a history of any type of eye surgery were excluded.
Fluorescein (FL; 1%) staining of the corneal and conjunctival staining with scores ranging from 0 to 9 (FL-S), and the tear film break-up time (BUT in sec) were measured according to the 2006 Japanese Dry Eye Diagnostic Criteria.8 The measurements were made by the same two ophthalmologists (A.S. and M.Y.).
The presence of LWEs at the upper and lower eyelid margins was also determined by FL (1%) and LG staining (2%) (grades 0 to 3 after Korb et al.1–3). The correlations between the prevalence and the grade of LWEs, and age, sex, BUT, and FL-S were determined.
All data are presented as the means±standard error of the means. Statistical analyses were performed with JMP for Windows, Version 8 (SAS Institute, Cary, NC). A P value less than 0.05 was considered statistically significant.
Lid-Wiper Epitheliopathy in Non-Contact Lens Wearers
Four hundred forty-three eyes of 229 non-CL wearers (100 men and 129 women, age 3–94 years with a mean of 52.1±24.0 years [mean±SD]) were studied. The upper-LWE (grades 1–3) was detected in 55 (12.5%) of 443 eyes along the margin of the upper eyelid and in 174 (39.5%) of 443 eyes along the lower eyelid margin (lower-LWE) in non-CL wearers (Fig. 1).
The prevalence of lower-LWE was significantly higher in these non-CL wearers than that of upper-LWE (P<0.001; Table 1). The average LWE grade of the upper-LWE was 0.21±0.03, which was significantly lower than the lower-LWE score of 0.79±0.05 (P<0.001; Table 1).
All of the subjects were divided into those with LWE [LWE(+)] and those without LWE [LWE(−)], and the significance of the differences in the different parameters of the subjects was determined for these two groups. The LWE(+) group was significantly younger than that of LWE(−) group for both upper- and lower-LWE. No significant difference was detected for sex and BUT between the two groups. However, the FL staining scores were significantly higher in the LWE(+) group than in the LWE(−) group for both the upper- and lower-LWE (Table 2).
Because a significant difference was found in the ages between the LWE(+) and LWE(−) groups, the prevalence and average LWE scores of the eyes with LWE were examined in more detail by dividing the subjects into 20-year age groups. Both the prevalence and average LWE grading scores decreased significantly with increasing age (P<0.0001), and the most significant difference was detected between the 0 to 19 years and 20 to 39 years for the upper-LWE and between the 20 to 39 and 40 to 59 years for the lower-LWE (Fig. 2A, B). When the subjects were divided into younger (≤39 years) and older (>40 years) groups, both the prevalence and average LWE scores were significantly higher in the younger groups for both upper-LWE and lower-LWE (Fig. 2C, D).
Lid-Wiper Epitheliopathy in CL Wearers
Two hundred seventy eyes of 137 SCL wearers (35 men and 102 women, age 9–61 years, and mean 26.5±10.5 years) and 135 eyes of 71 RGPCL wearers (11 men and 60 women, age 14–61 year, and mean 37.0±11.8 years) were studied. The prevalence and grade of either type of LWE was significantly higher in the CL wearers than in the non-CL wearers. The prevalence and grade of upper-LWE was RGPCL>SCL while that of the lower-LWE was similar in RGPCL and SCL (Fig. 3).
The FL staining score was significantly higher in the LWE(+) group but not in the lower-LWE(+) group of the RGPCL wearers. No difference was detected in BUT scores in either the LWE(+) and LWE(−) groups, but the BUT score was higher in the upper-LWE group (−) of the SCL wearers (Table 3).
Our results showed that LWE was relatively common in CL wearers and non-CL wearers. One of new findings was that LWE-like staining was found at the lower eyelid margins (lower-LWE) and not only in the upper lid margins. However, the prevalence of lower-LWE was higher than upper-LWE. Another new finding was that a higher prevalence of both upper- and lower-LWE was present in younger than older individuals, and the prevalence and severity of LWE decreased with increasing age. We found that upper-LWE was present in 12.5% of non-CL wearers. Because we did not question the subjects about having dry eye symptoms or having been diagnosed with the dry eye syndrome, the prevalence of upper-LWE in this study may be more comparable with that in nonsymptomatic subjects in the earlier studies.2,3,9
As Korb et al.2,7 mentioned, the probable cause of LWE is a compromised tear film resulting from inadequate lubrication between the eyelid and ocular surface.9 The higher prevalence of LWEs in CL wearers supports this suggestion because the tear film instability during CL wear has been well documented.10–13 Another possibility of the higher prevalence of LWEs in CL wearers may be because of higher shear stress between the eyelids and CL because the surface of CL has more friction compared with corneas. The higher prevalence of LWEs in younger generations may support the hypothesis of higher shear stress. In a recent study, we demonstrated that the eyelid pressure was higher in younger individuals and decreased with increasing age. In addition, both the upper and lower eyelid pressures were significantly and negatively correlated with age.14 Although eyelid pressure does not directly reflect the shear stress generated by the eyelids, it may partly be related to the share stress generated by the eyelids. These findings support the hypothesis that shear stress from the eyelids was involved in the development of LWEs.
One of the purposes of this study was to determine the cause of or the risk factors for LWE. Upper-LWE has been observed frequently in patients with dry eye or dry eye symptoms,1–3,5,9 and thus, dry eye has been considered to be a risk factor of LWE. However, not all patients with LWE had tear deficiency in the earlier studies.5,9 In our study, no difference was detected in the BUT values between LWE(+) and LWE(−) groups, and longer BUTs were detected in the lower-LWE(+) group than the LWE(−) groups among the SCL wearers. These results confirmed an earlier report that no difference was detected in any of dry eye tests, including the Shirmer test, BUT, and DR-1 among LWE(+) and LWE(−) groups.5 Thus, these results indicate that dry eye may not be the only risk factor for LWEs although patients with LWEs can have dry eye. It will be necessary to examine and determine whether dry eye causes LWEs or LWEs cause the dry eye symptoms.
Interesting findings in this study were that the prevalence and grade of lower-LWE were significantly higher than those of upper-LWE. During a blink, the upper eyelid has a large vertical movement while the lower lid has a shorter horizontal nasalward movement.15 Because of the large excursion of the upper eyelid, most investigators have paid more attention to the pressures generated by the upper eyelid movements. Among the limited number of studies that examined the effects of lower eyelid movements, Shore16 reported that the decrease in lower eyelid movement with aging was closely correlated with the increase in eyelid laxity. However, it should also be remembered that the lower eyelid moves horizontally meaning that the eyelid margin rubs over the same area of the cornea and conjunctival surface. Thus, the friction of the eyelid movements on a restricted area of ocular surface might be greater by the lower eyelid than the upper eyelid. The lower-LWE is generally found at the nasal margin of the palpebral conjunctiva in the vicinity of the lower punctum (Fig. 1). This area moves against the surface of the bulbar conjunctiva, whereas the area of predilection of the upper-LWE is the middle of the eyelid that moves over a smooth corneal surface. These different locations of the movements may be another reason for the higher prevalence of lower-LWE. This hypothesis may be partly supported by some of the reports discussing lid-parallel conjunctival folds (LIPCOF), which are subclinical folds in the lateral, lower quadrant of the conjunctiva parallel to the lower lid margin, and are suggested to be the first mild stages of conjunctivochalasis. In a series of reports,17,18 the presence of LIPCOF was significantly correlated with dry eye symptoms along with LWE (upper-LWE). Thus, it has been suggested that both clinical signs are related to mechanical stress caused by rubbing.18–20 Among those, Pult et al.18 reported that nasal LIPCOF was related to dry eye symptoms. Although no report has reported on the relationship between lower-LWE and nasal LIPCOF, they may be significantly correlated. Future clinical studies including impression cytology are needed to understand the pathogenesis of LWE and LIPCOF.
Regarding the cause of LWE, we had a 33-year-old woman who presented with eye redness, discharge, asthenopia, and headaches. On her first visit, she wore SCL on her right eye but had not been worn SCL on left eye for 1 month because of severe eye pain. Slitlamp examination revealed upper-LWE on her right eye but not on her left eye (Fig. 4A, B), whereas lower-LWE was detected on both eyes (Fig. 4A, B). She was directed to stop wearing SCL and also to use 0.1% hyaluronic acid eye drops. These treatments resulted in the disappearance of the upper-LWE, but the lower-LWE remained on her right eye (Fig. 4C). In addition, most of the symptoms abated. Because she felt better, she expressed a desire to wear SCL again. Under informed consent that re-wearing SCL might induce LWE and the symptoms, she should be examined regularly if she chose to wear SCL again. Two months later she visited us after she had been wearing SCL on both eyes for 3 consecutive days. Slitlamp examination showed upper-LWE and unchanged lower-LWE on both eyes (Fig. 5A, B). The course of this case, that is, the disappearance of upper-LWE by discontinuing SCL on her right eye, and re-appearance of upper-LWE on both eyes by re-wearing SCL, proved the involvement of SCL as the cause of upper-LWE. An interesting finding in this case was the presence of lower-LWE regardless of SCL wear. It is likely that the palpebral conjunctival epithelium of the lower eyelid margin is more sensitive or fragile to the higher eyelid pressure and continuous friction. The presence of lower-LWE may be a risk factor of upper-LWE when wearing a CL.
In conclusion, we found that the prevalence of LWEs in randomly selected patients who visited the ophthalmological outpatient clinic was higher for lower-LWE than upper-LWE. The higher prevalence of lower-LWE may be caused by the continuous friction of the lower eyelid on the same region of the cornea during blinking. More attention should be paid to the lower eyelid margins and movements during blinking.
Involved in design and conduct of study (A.S.); data collection (A.S., M.Y.); analysis and interpretation of the data (A.S); writing (A.S.); critical revision (Y.O.); and literature search (A.S.) of the manuscript. The study was approved by the Institutional Review Board of Ehime University. An informed consent for the examination was obtained from all subjects, and the procedures used conformed to the tenets of the Declaration of Helsinki.
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