BASIC INVESTIGATION
Lid Margin Sensitivity and Staining in Contact Lens Wear Versus No Lens Wear Maria Navascues-Cornago, BSc, MSc, Philip B. Morgan, BSc, PhD, MCOptom, FAAO, and Carole Maldonado-Codina, MSc, PhD, MCOptom, FAAO
Purpose: To map the sensitivity and staining of the marginal conjunctiva in soft contact lens (SCL) wearers and nonwearers and to investigate diurnal changes.
Methods: Thirty-five nonwearers and 35 SCL wearers were recruited. Mechanical sensitivity was measured at 8 locations on the ocular surface and adnexa (cornea, marginal, bulbar, and tarsal conjunctivae) using the Cochet–Bonnet aesthesiometer. Lid margin staining (lissamine green) was assessed through image analysis. Measurements were repeated at 12 hours in 11 nonwearers and 10 symptomatic SCL wearers. Results: The marginal conjunctiva was the most sensitive conjunctival region (all P , 0.001). There was no significant difference in sensitivity at 12 hours (all P . 0.05). There was a significant difference in sensitivity between the 2 groups in the morning for the lower lid tarsal conjunctiva (P = 0.003). After 12 hours, the sensitivity of the lower lid marginal conjunctiva was found to be reduced in SCL wearers compared with nonwearers (all P , 0.05). Lower lid margin staining was greater than upper lid margin staining in both groups (all P , 0.05). In the SCL wearers, a significant increase in lower lid margin staining was found at 12 hours compared with the morning (P = 0.04). After 12 hours, lower lid margin staining was significantly greater in SCL wearers compared with nonwearers (P = 0.03).
Conclusions: This work has demonstrated that the marginal conjunctiva is the most sensitive conjunctival region. After 12 hours, symptomatic lens wearers showed decreased sensitivity of the lower marginal conjunctiva and increased lower lid margin lissamine green staining compared with those of the nonwearers. Key Words: marginal conjunctiva, ocular surface sensitivity, contact lenses, Cochet-Bonnet aesthesiometer, lid margin staining (Cornea 2015;34:808–816)
Received for publication September 23, 2014; revision received February 24, 2015; accepted February 28, 2015. Published online ahead of print May 1, 2015. From Eurolens Research, Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom. This work forms part of a self-funded PhD program of research. The authors have no funding or conflicts of interest to disclose. Reprints: Maria Navascues-Cornago, BSc, MSc, Eurolens Research, Carys Bannister building, The University of Manchester, Dover St, Manchester M13 9PL, United Kingdom (e-mail: maria.navascuescornago@manchester. ac.uk). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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ontact lens discomfort (CLD) is the primary reason for discontinuation from contact lens wear.1,2 CLD is characterized by a series of adverse sensations related to lens wear that may lead to decreased comfortable wearing hours, a reduction in total wearing time and discontinuation from lens wear.3 Many factors have been related to CLD, such as lens modulus, surface properties, design and fit, care system,4 tear film characteristics,5 and contact lens–related pathology such as giant papillary conjunctivitis.6 Comprehensive recent reviews of this area have been provided by the TFOS International Workshop on Contact Lens Discomfort7 and Chalmers.8 Despite this extensive research base and major reviews of the field, the etiology of CLD still remains unclear. One CLD factor that has recently received attention is the lid margin and its interaction with the contact lens surface. The lid margin is divided into 3 distinct anatomical subzones: the skin epidermis extending over the meibomian gland orifices, the mucocutaneous junction (transition region between the skin epidermis and the conjunctival tissue, the surface that represents the line of Marx), and the marginal conjunctiva, also known as the “lid wiper.” The marginal conjunctiva is a prominent epithelial thickening of the inner lid border that gradually decreases toward the subtarsal fold. The marginal conjunctiva is believed to be the only region of the lid margin that is apposed to the globe and to be responsible for the spread of the tear film over the ocular surface (or lens surface) during blinking.9 Staining of the lid margin has been associated with symptoms of discomfort and dryness in soft contact lens (SCL) wearers and in patients with dry eye.10–13 There is no strong evidence of greater lid margin staining in SCL wearers than in nonwearers.11,14 Although the etiology of lid margin staining remains unclear, it has been hypothesized that it may result from increased frictional forces between the lid margin and the ocular or lens surface during blinking when the lubrication is inadequate.10,12,13 Although a correlation between corneal and conjunctival sensitivity and staining of the ocular surface has been reported in patients with dry eye,15 previous studies investigating the relationship between lid margin staining and sensitivity in healthy subjects without contact lenses were unable to find any association.16 Furthermore, the relationship between lid margin staining and conjunctival mechanical thresholds has not been fully investigated in SCL wearers. The purpose of this work was to map the sensitivity of the marginal and tarsal conjunctivae of the upper and lower eyelids and bulbar conjunctival regions in SCL wearers and Cornea Volume 34, Number 7, July 2015
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Cornea Volume 34, Number 7, July 2015
nonwearers and to investigate whether the sensitivity of these areas changed over a 12-hour period. Lid margin staining and its relationship with sensitivity of the marginal conjunctiva were determined.
METHODS Study Design This study was randomized, controlled, and subject masked. Ethical approval for performing this work was obtained from the University of Manchester Committee on the Ethics of Research on Human Beings. The study was conducted in accordance with the tenets of the Declaration of Helsinki. All subjects were given information about the study before they signed a consent form to participate.
Subjects To determine the study sample size, power analysis was performed using data from a previous pilot investigation. If 33 subjects completed the study, the study would have 80% power to detect a 1-cm difference in sensitivity using a Cochet–Bonnet aesthesiometer, assuming an alpha of 0.05, a 2-tailed paired analysis, and an SD of differences 2.0. To allow for subject discontinuations, 35 nonwearers and 35 SCL wearers were recruited for the morning visit. If 10 subjects completed the end-of-day visit, the study would have 80% power to detect a 1-cm difference in sensitivity over the course of the day, assuming an alpha of 0.05, a 2-tailed paired analysis, and an SD of differences 1.0. The exclusion criteria were any systemic or ocular disorder that may affect ocular health, grade 2 or greater of any anterior ocular clinical signs, use of any topical medication such as eye drops or ointment, previous cataract or corneal refractive surgery, and being pregnant or lactating. Nonwearers should never have previously worn contact lenses for more than 2 weeks. Contact lens wearers must be wearing SCLs on a daily wear basis (a minimum of 8 hours per day, 5 days per week) for a period of at least 6 months.
Experimental Protocol All subjects attended a morning visit, and a subset was asked to attend an end-of-day visit. The first 11 nonwearers and 10 symptomatic SCL wearers who satisfied the inclusion criteria and were willing to participate in the second visit at 12 hours were selected. At the morning visit, all measurements were taken at least 2 hours after waking to minimize any issues related to overnight corneal edema.17 Contact lens wearers were asked to attend this visit without any lenses in situ (and not having worn lenses beforehand on the day). Details of the ocular history were recorded, and an anterior eye examination was undertaken. Only SCL wearers completed the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8)18 and were classified as either asymptomatic or symptomatic by the criteria set by Young et al.19 Briefly, subjects were classified as symptomatic or asymptomatic based on their responses to frequency Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Lid Margin Sensitivity and Staining
and intensity of dryness symptoms. Eighteen subjects were classified as symptomatic SCL wearers. The overall subjective comfort for their habitual contact lenses was recorded using an annotated vertical analog grading scale where 0 represented “cannot be tolerated” and 100 represented “cannot be felt.” Lid margin staining was assessed using lissamine green strips (GreenGlo; Hub Pharmaceuticals LLC, Rancho Cucamonga, CA) soaked for 1 minute in 0.9% sterile saline (Eye Care solutions; Crest Medical Ltd, Warrington, United Kingdom) and applied to the conjunctival sac. Four minutes from the first instillation, the same procedure was repeated. One minute from the last instillation, images of the lissamine green staining of the upper and the lower eyelid were taken with a slit lamp (SL-D4; Topcon, Tokyo, Japan), under white light, using ·10 magnification, and a slit-lamp beam width of approximately 14 mm. The area of lissamine green staining was recorded by analyzing digital images of the right eye using ImageJ (V.1.46; National Institutes of Health, USA, http://rsbweb.nih.gov/ij/). The lid margin staining area was defined as the area of lissamine green staining that extended from the lacrimal punctum to the temporal canthus and from the line of Marx to the subtarsal fold.10 The area of the line of Marx, which is represented as a thin line of lissamine green staining (0.1 6 0.1 mm)20 visible in most healthy eyes, was included in the measurement of the lid margin staining area. For the upper lid examination, the upper eyelid was everted, always being careful not to contact the area of the lid margin staining. Mechanical thresholds of the ocular surface were measured using a Cochet–Bonnet aesthesiometer (Luneau Ophtalmologie, Paris, France) with a 0.1 mm-diameter nylon filament. The Cochet–Bonnet aesthesiometer was mounted on a slit lamp to allow accurate application of the stimulus with the aid of the magnification observation system, which ensured that the filament approached the ocular surface smoothly and perpendicularly. Calibration and mechanical thresholds were determined using the ascending method of limits, which has been described in a previous study.21 Four stimuli were presented at each filament length, and the length that gave 2 or more positive responses was taken to be the mechanical threshold. Mechanical thresholds were determined at the following locations: central cornea, temporal bulbar conjunctiva (approximately 3 mm from the limbus), upper and lower marginal conjunctivae (central and temporal approximately 5 mm from the center), and upper and lower tarsal conjunctivae (approximately 2 mm posterior to the line of Marx). Because the measurement of the sensitivity using the Cochet–Bonnet aesthesiometer is a time-consuming procedure for subjects, the sensitivity was only determined at temporal locations (and not at nasal locations), and this was considered representative of the off-center sensitivity. The order of assessment of each of these locations was randomized. Complete eversion of the upper eyelid and partial eversion of the lower eyelid were required to measure the sensitivity of the marginal and tarsal conjunctivae. The exact location of the sensitivity measurement for the marginal conjunctiva depended on whether there was www.corneajrnl.com |
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lissamine green staining of the lid margin. When the lid margin displayed an area of staining, the sensitivity was measured in the middle of the staining (in a vertical direction). If only the line of Marx was stained, the sensitivity was measured approximately 0.1 mm posterior to the line of Marx. An eyepiece graticule (Eyepiece BM 10·; Haag-Streit AG, Koeniz, Switzerland) was used at ·10 magnification to perform these measurements accurately. At the end of the visit, when all clinical measurements were completed, a subgroup of 10 symptomatic SCL wearers used their own contact lenses and wore them for 12 hours during which time they conducted their normal daily routine. Comfort scores were recorded once their contact lenses were worn. Repeated measurements were taken at 12 hours in these subjects and in a further subgroup of 11 nonwearers. Subjective lens comfort was assessed at the start of this end-of-day visit using the 100-point vertical analog scale. Lens fit was assessed by horizontal and vertical centration, movement (in primary gaze after a blink), and corneal coverage.22 Contact lenses were then removed (if applicable), and measurements were immediately repeated for sensitivity and lid margin staining as occurred at the morning visit. All measurements were taken at normal conditions of temperature (range, 18.6– 24.7°C) and relative humidity (range, 30%–54.8%).
TABLE 1. Post Hoc Power Analysis SD Alpha Difference, cm Power Differences in sensitivity between locations Diurnal differences in sensitivity
Nonwearers SCL wearers Nonwearers SCL wearers
1.2 1.4
0.05 0.05
1 1
0.9986 0.9862
0.6 1.1
0.05 0.05
1 1
0.9986 0.7566
and overall lens comfort scores were significantly negatively correlated (Spearman r = 20.58, P , 0.001). There was a decrease in subjective comfort after 12 hours of lens wear in the subgroup of symptomatic SCL wearers (92.8 6 7.8 vs. 68.3 6 15.6, Wilcoxon signed-rank test, P = 0.005). Lens-fitting characteristics after 12 hours of lens wear were optimum to slightly inadequate (centration 0.0 6 0.2; coverage 0.2 6 0.1; and movement 0.1 6 0.1). Clinical measurements were taken in the morning in all subjects. Measurements were repeated at 12 hours in a subgroup of 11 nonwearers (6 women and 5 men; mean age: 28.9 6 9.9 years, range: 22–57 years) and 10 symptomatic SCL wearers (5 women and 5 men; mean age: 26.5 6 7.9 years, range: 20–40 years).
Statistical Analysis
Lid Margin Staining
Only data for the right eye were included in the analyses. Statistical analyses were performed using SPSS Statistic version 20 (IBM Corp, Armonk, NY). The Shapiro–Wilk test showed that variables were not normally distributed, and therefore, nonparametric analysis was performed. The Friedman test was used to analyze sensitivity data at the various ocular locations. Any significant difference was further investigated using the Wilcoxon signed-rank test. Differences in sensitivity at 12 hours and lid margin staining were also analyzed using the Wilcoxon signed-rank test. The Mann–Whitney U test was used to analyze differences in variables between nonwearers and SCL wearers. Correlation between variables was analyzed using Spearman rank correlation coefficients. P , 0.05 was considered statistically significant. Bonferroni correction was used to adjust the level of significance when multiple comparisons were performed to avoid type 1 errors.
Thirty-five nonwearers and 35 SCL wearers were enrolled in the study. Post hoc power analysis was calculated using the typical SD observed in the present data and assuming a 2-tailed analysis and an alpha of 0.05 (Table 1). Demographic details of subjects are shown in Table 2. There were no significant differences in demographics between nonwearers and SCL wearers (all P . 0.05) or between symptomatic and asymptomatic SCL wearers (all P . 0.05). As expected, CLDEQ-8 scores were higher for the symptomatic group compared with the asymptomatic group (unpaired t test, P , 0.001), and there was a significant difference in overall lens comfort between the 2 groups (Mann–Whitney U test, P , 0.001). CLDEQ-8 scores
Digital images that were not considered clear enough to be analyzed with ImageJ were discarded. Therefore, in the nonwearers, the number of images analyzed was as follows: 34 images of the upper eyelid and 34 images of the lower eyelid from the morning visit; and 10 images of the upper eyelid and 11 images of the lower eyelid at the end-of-day visit. All pictures were considered suitable for analysis in the SCL wearers. Figure 1 shows the area of lid margin staining for the nonwearers and SCL wearers in the morning. Lid margin staining was significantly greater for the lower eyelid compared with that of the upper eyelid in the morning for both groups (Wilcoxon signed-rank test, nonwearers, P = 0.002, SCL wearers, P = 0.001) and at the end of the day only for the nonwearers (Wilcoxon signed-rank test, P = 0.005). A comparison of lid margin staining between the morning and the end of the day is represented in Figure 2. In the nonwearers, no significant change was found in lid margin staining over 12 hours (Wilcoxon signed-rank test, all P . 0.05). In the SCL wearers, a significant increase was found at 12 hours only for the lower eyelid (Wilcoxon signed-rank test, P = 0.04). The staining of the upper and lower eyelids was marginally correlated in the nonwearers (Spearman r = 0.33, P = 0.06), and it was positively correlated in the SCL wearers (Spearman r = 0.55, P = 0.001). There was no correlation between lid margin staining and CLDEQ-8 and/or lens comfort scores (Spearman, all P . 0.05). Lid margin staining was not significantly different between symptomatic and asymptomatic SCL wearers (Mann–Whitney U test, all P . 0.05) (Fig. 3).
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RESULTS
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Cornea Volume 34, Number 7, July 2015
Lid Margin Sensitivity and Staining
TABLE 2. Demographic Details of Subjects Attending the Morning Visit Nonwearers (n = 35)
All SCL Wearers (n = 35)
Age (mean 6 SD), yr Gender CL experience (mean 6 SD), yr CL material CL design CL replacement frequency
27.7 6 7.3 20 F, 15 M NA NA NA NA
CLDEQ-8 score (mean 6 SD) Overall lens comfort score (mean 6 SD)
NA NA
25.6 6 7.4 21 F, 14 M 7.4 6 7.1 23 H, 12 SH 29 sphere, 6 toric 18 daily, 14 monthly, 2 bi-weekly, 1 yearly 11.7 6 5.4 80.9 6 15.1
P
Symptomatic SCL Wearers (n = 18)
0.24 25.0 6 6.5 0.81 10 F, 8 M NA 5.7 6 5.6 NA 13 H, 5 SH NA 15 sphere, 3 toric NA 10 daily, 7 monthly, 1 yearly NA NA
15.4 6 3.7 73.0 6 16.4
Asymptomatic SCL Wearers (n = 17) 26.2 6 8.4 11 F, 6 M 9.3 6 8.1 10 H, 7 SH 14 sphere, 3 toric 8 daily, 7 monthly, 2 bi-weekly 7.8 6 4.1 89.2 6 7.3
P 0.62 0.58 0.1 0.4 1 0.76 ,0.001 ,0.001
Bold values indicate a significant difference, P , 0.05. CL, contact lens.
Lid margin staining was not significantly different between nonwearers and SCL wearers in the morning (Mann–Whitney U test, all P . 0.05) (Fig. 1). Twelve hours later, there was no significant difference in lid margin staining between the 2 groups for the upper lid (Mann–Whitney U test, P = 0.08), but the staining of the lower lid was significantly greater in the SCL wearers compared with the nonwearers (Mann–Whitney U test, P = 0.03) (Fig. 2).
Sensitivity Thresholds Table 3 shows mechanical thresholds for the various stimulus locations in the morning and at the end of the day.
There was a significant difference in sensitivity between the various ocular locations in both groups (Friedman, all P , 0.001). In both groups, the cornea was the most sensitive region (Wilcoxon signed-rank test, P , 0.001). The marginal conjunctiva was more sensitive than the bulbar and tarsal conjunctivae (Wilcoxon signed-rank test, P , 0.001). The temporal marginal conjunctiva was more sensitive than the central marginal conjunctiva in nonwearers (Wilcoxon signed-rank test, P , 0.05). The upper tarsal conjunctiva was more sensitive than the lower tarsal conjunctiva in both groups (Wilcoxon signed-rank test, P , 0.05). There was a significant difference in sensitivity between the 2 groups in the morning for the tarsal
FIGURE 1. Box and whisker plots comparing lid margin staining between nonwearers (n = 34) and SCL wearers (n = 35) in the morning. The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Cornea Volume 34, Number 7, July 2015
FIGURE 2. Box and whisker plots comparing lid margin staining in the morning and at the end of the day in nonwearers (n = 10) and symptomatic SCL wearers (n = 10). The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range.
conjunctiva of the lower eyelid (Mann–Whitney U test, Bonferroni-adjusted P , 0.006). Mechanical thresholds measured at the end of the day are compared with those in the morning in Table 4. No significant difference in sensitivity was found between the morning and the end of the day for any of the locations (Wilcoxon signed-rank test, Bonferroni-adjusted, all P . 0.006) within each. After 12 hours, sensitivity of the lower lid marginal conjunctiva was found to be reduced in the SCL wearers compared with the nonwearers (Mann–Whitney U test, Bonferroni-adjusted, all P , 0.006). Mechanical thresholds were not significantly different between asymptomatic and symptomatic SCL wearers at the morning visit (Mann–Whitney U test, Bonferroni-adjusted, all P . 0.006) and were not correlated with CLDEQ-8 and/or comfort scores (Spearman, all P . 0.05). At the end of the day, the mechanical threshold of the temporal marginal conjunctiva of the lower eyelid was negatively correlated with lid margin staining only in the nonwearers (Spearman r = 20.683, P = 0.03).
This study investigated the sensitivity of the cornea and conjunctiva at different locations and compared them across a 12-hour period and between groups of SCL wearers and nonwearers. Lid margin staining and its relationship with sensitivity of the marginal conjunctiva were also determined.
Lid margin staining assessed in the morning was greater for the lower eyelid compared with that of the upper eyelid in both nonwearers and SCL wearers, which has been previously reported in nonwearers.16 Although lid margin staining was similar between SCL wearers and nonwearers in the morning, the staining of the lower lid margin was significantly greater in the symptomatic SCL wearers compared with the nonwearers at the end of the day. Lid margin staining of the upper eyelid is believed to be induced by mechanical microtrauma of the marginal conjunctiva during blinking resulting from inadequate lubrication between the lid margin and the ocular surface.10,12,13 It is reasonable to expect the upper eyelid to display increased staining at the end of the day compared with that at the morning as a result of thousands of daily blinks.23 However, the staining of the upper lid margin did not show a significant diurnal change in this study (for either group), whereas the staining of the lower lid increased at the end of the day in symptomatic SCL wearers. This finding supports the hypothesis that the mechanism for staining of the upper lid margin may be different from that for the lower lid. Indeed, lid margin staining may not be produced as a result of microtrauma. Previous studies have hypothesized that lower lid margin staining may be caused by chemical injury as a result of the pooling of tears in the lower meniscus leading to a longer interaction with the dye and/or to longer exposure to inflammatory mediators of tears,16 although this has not been demonstrated yet. Additionally, the lower eyelid also moves during blinking24 and it is still unknown how this
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DISCUSSION
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Cornea Volume 34, Number 7, July 2015
Lid Margin Sensitivity and Staining
FIGURE 3. Box and whisker plots comparing lid margin staining in the morning between asymptomatic (n = 17) and symptomatic (n = 18) SCL wearers. The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range.
predominantly horizontal movement and its interaction with the contact lens could affect the integrity of the lid margin. Although lid margin staining was numerically greater in the symptomatic SCL wearers compared with the asymptomatic SCL wearers at the morning visit, this difference was not statistically significant. Although staining of the upper lid margin has been consistently associated with symptoms of dryness in SCL wearers,10,11,13 previous investigations have failed to demonstrate such an association for the staining of the lower eyelid.12,13 Differences among studies may be due to disparities in the methodology, that is, the vital dye(s) used and the grading method. Post hoc power analysis for 3 of the 4 variables suggests that the study comfortably held sufficient statistical power for meaningful differences to be detected. For the fourth variable—the diurnal change in sensitivity for the SCL wearers—the calculated power was just below the normal threshold adopted in clinical studies at 0.8. This value may also overestimate statistical power because our power calculations are based on parametric methods and nonparametric approaches were used in our analysis. As such, caution needs to be applied in drawing a conclusion on diurnal sensitivity for this group. A limitation of the Cochet–Bonnet aesthesiometer that may have affected the results of this study is its truncated stimulus intensity range. Previous studies have shown that corneal thresholds in some subjects may be outside the stimulus intensity range delivered by the 0.1-mm-diameter filament, which results in an underestimation of corneal Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
sensitivity.25,26 In this study, thresholds in the morning were at the measurable limit of the filament in 82.9% of nonwearers and 85.7% of SCL wearers for the cornea and 20% to 51.4% of nonwearers and 17.1% to 37.1% of SCL wearers for the marginal conjunctiva. For the subgroup of nonwearers and SCL wearers, thresholds in the morning were at the maximum filament length in 100% and 80% of subjects, respectively, for the cornea and 18.2% to 63.6% and 30% to 50% of subjects, respectively, for the marginal conjunctiva. The large proportion of subjects who had thresholds at the limit of detection may have affected the ability to determine differences in sensitivity between groups and between time points for the most sensitive ocular regions (ie, the cornea and marginal conjunctiva). However, those differences that are reported to be statistically significant can be considered to be real. Despite this limitation, this instrument was considered the most suitable to assess the sensitivity in this study because it was necessary to stimulate very specific ocular regions (particularly the marginal conjunctiva), which only could be achieved using this device. Although the noncontact corneal aesthesiometer may be able to measure at levels below the limits of the Cochet–Bonnet aesthesiometer,25,26 the size and location of the stimulated area is not completely defined.27 In line with previous investigations, the marginal conjunctiva was more sensitive than the bulbar and tarsal conjunctivae.28,29 Morphological studies investigating the sensory innervation of the human eyelid revealed a greater density of nerve endings present in the lid margin area,30 which may explain the increased sensitivity of the marginal www.corneajrnl.com |
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TABLE 3. Comparison of Median (Interquartile Range) Mechanical Thresholds Between Nonwearers and SCL Wearers in the Morning (n = 35 vs. n = 35) and at the End of Day (n = 11 vs. n = 10) Stimulus Location Cornea
Bulbar conjunctiva
Upper lid central marginal conjunctiva Upper lid temporal marginal conjunctiva Lower lid central marginal conjunctiva Lower lid temporal marginal conjunctiva Upper lid tarsal conjunctiva
Lower lid tarsal conjunctiva
Time Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day
Nonwearers, mN
% of Thresholds at the Limit (ie, 6 cm)
SCL Wearers, mN
% of Thresholds at the Limit (ie, 6 cm)
P
0.2 (0.2–0.2) 0.2 (0.2–0.2)
82.9 100
0.2 (0.2–0.2) 0.2 (0.2–0.3)
85.7 70
0.85 0.06
1.2 (0.9–1.9) 0.7 (0.4–1.8)
0 9.1
1.2 (0.7–8.7) 1.0 (0.4–10.6)
2.9 10
0.69 0.62
0.4 (0.2–0.5) 0.2 (0.2–0.3)
25.7 63.6
0.3 (0.2–0.5) 0.3 (0.2–0.5)
37.1 30
0.84 0.1
0.2 (0.2–0.4) 0.2 (0.2–0.3)
51.4 54.5
0.4 (0.2–0.5) 0.3 (0.2–0.6)
34.3 40
0.07 0.35
0.4 (0.3–0.4) 0.2 (0.2–0.3)
20 54.5
0.3 (0.3–0.5) 0.6 (0.4–0.9)
17.1 10
0.95 0.005
0.3 (0.2–0.4) 0.2 (0.2–0.2)
31.4 81.8
0.3 (0.2–0.5) 0.5 (0.3–0.8)
37.1 20
0.56 0.003
0.9 (0.5–1.8) 0.5 (0.4–0.9)
0 0
1.8 (0.7–8.7) 2.4 (0.7–10.6)
5.7 20
0.06 0.08
1.8 (0.7–3.6) 0.9 (0.4–8.7)
2.9 9.1
8.7 (1.8–16.3) 5.3 (0.4–18.5)
2.9 0
0.003 0.32
Bold values indicate a significant difference, Bonferroni-adjusted P , 0.006.
conjunctiva compared with that of the tarsal conjunctiva. In this study, no significant change was found in the ocular surface sensitivity after a 12-hour period in nonwearers. This is contrary to previous studies that have shown an increase in corneal sensitivity throughout the day.17,31 One fact that may explain these differences is that greater changes in corneal sensitivity may occur on eye opening upon awakening,17,31 but in this study, to minimize the effect of overnight corneal swelling on sensitivity measurements, thresholds were measured at least 2 hours after the subjects awoke.17 The wear of contact lenses over a 12-hour period had no significant impact on mechanical thresholds of the ocular surface in the symptomatic subjects. In addition, the sensitivity measured in the morning was similar between nonwearers and SCL wearers for most of the regions, except for the inferior tarsal conjunctiva, which was less sensitive in the SCL wearers. Previous studies using the Cochet–Bonnet aesthesiometer have shown decreased corneal sensitivity after short-term and long-term wear of rigid gas-permeable,32,33 poly-methyl methacrylate (PMMA),32–34 and conventional hydrogel contact lenses.35–37 Reduced sensitivity of the tarsal conjunctiva and lid margin with rigid gas-permeable, PMMA, and conventional hydrogel contact lenses has also been reported.38,39 For silicone hydrogel lenses, previous studies have shown either no change40 or a decrease41 in corneal sensitivity, whereas no change has been reported for the sensitivity of the bulbar conjunctiva.41 The exact mechanism responsible for changes in the ocular surface sensitivity as
a result of contact lens wear is unclear. Sensory changes have been attributed to metabolic disorders caused by lens-induced hypoxia,32,35 neural adaptation to mechanical stimulation,32,41 and neural sensitization in response to inflammation or hyperosmolarity.41 Studies based on x-ray examinations have shown that only the lid margin of the upper eyelid is directly in contact with the ocular surface, whereas the entire tarsal area of the lower eyelid is in close apposition with the globe.42 The interaction between the lens and the tarsal area could have affected the sensitivity of this area. Nonetheless, the difference in sensitivity of the inferior tarsal conjunctiva between SCL wearers and nonwearers was only significant during the morning. Considering that recovery of sensitivity may occur within a few hours after stopping lens wear35,36 and the fact that all lenses were used on a daily wear basis, it is perhaps not unexpected to have found no difference in sensitivity between SCL wearers and nonwearers in the morning. The reduced sensitivity of the lower lid marginal conjunctiva found in SCL wearers compared with nonwearers at the end of the day is a surprising finding considering that such a difference was not found for the upper lid marginal conjunctiva. If we consider a mechanical etiology for the reduction in sensitivity, it would be expected that the upper lid marginal conjunctiva was more affected given its continuous interaction with the lens surface during blinking. However, the movement of the lower eyelid and its interaction with the lens surface could affect the sensitivity of the
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Cornea Volume 34, Number 7, July 2015
Lid Margin Sensitivity and Staining
TABLE 4. Comparison of Median (Interquartile Range) Mechanical Thresholds in the Morning and at the End of Day for Nonwearers (n = 11) and SCL Wearers (n = 10) Location
Group
Cornea
Morning, mN
Nonwearers 0.2 SCL wearers 0.2 Bulbar conjunctiva Nonwearers 0.9 SCL wearers 0.6 Upper lid central marginal conjunctiva Nonwearers 0.3 SCL wearers 0.3 Upper lid temporal marginal conjunctiva Nonwearers 0.2 SCL wearers 0.3 Lower lid central marginal conjunctiva Nonwearers 0.2 SCL wearers 0.3 Lower lid temporal marginal conjunctiva Nonwearers 0.3 SCL wearers 0.3 Upper lid tarsal conjunctiva Nonwearers 0.7 SCL wearers 1.5 Lower lid tarsal conjunctiva Nonwearers 0.9 SCL wearers 12.5
% of Thresholds at Limit % of Thresholds at Limit (ie, 6 cm) End of the Day, mN (ie, 6 cm)
(0.2–0.2) (0.2–0.3) (0.7–1.2) (0.4–4.8) (0.3–0.4) (0.2–0.5) (0.2–0.4) (0.2–0.5) (0.2–0.4) (0.2–0.5) (0.2–0.3) (0.2–0.6) (0.7–1.2) (0.5–16.3) (0.7–1.8) (0.4–16.3)
100 80 0 10 18.2 50 63.6 50 54.5 30 45.5 50 0 10 9.1 10
0.2 0.2 0.7 1.0 0.2 0.3 0.2 0.3 0.2 0.6 0.2 0.5 0.5 2.4 0.9 5.3
(0.2–0.2) (0.2–0.3) (0.4–1.8) (0.4–10.6) (0.2–0.3) (0.2–0.5) (0.2–0.3) (0.2–0.6) (0.2–0.3) (0.4–0.9) (0.2–0.2) (0.3–0.8) (0.4–0.9) (0.7–10.6) (0.4–8.7) (0.4–18.5)
100 70 9.1 10 63.6 30 54.5 40 54.5 10 81.2 20 0 20 9.1 0
P 1 1 0.67 0.31 0.01 0.25 0.79 0.42 0.75 0.01 0.18 0.18 0.07 0.16 0.78 0.88
Bold values indicate a significant difference, Bonferroni-adjusted P , 0.006.
lower lid margin. Further research is needed to understand the exact mechanism for sensory changes related to lens wear. The relationship between discomfort symptoms reported by contact lens wearers and changes in the sensitivity of the ocular surface is poorly understood. Symptomatic and asymptomatic SCL wearers showed similar mechanical thresholds. Investigations using the noncontact corneal aesthesiometer have also reported no clear association between symptoms and ocular sensitivity.43 A more recent investigation found corneal adaptation to suprathreshold stimuli in asymptomatic SCL wearers but not in symptomatic wearers, although there was no difference in thresholds between the 2 groups.44 All these findings show that the understanding of the relationship between CLD and sensitivity of the ocular surface is still limited. In summary, this study has demonstrated that the marginal conjunctiva is the most sensitive of all the conjunctival regions in SCL wearers and nonwearers alike. After a 12-hour period, SCL wearers showed decreased sensitivity of the lower marginal conjunctiva and increased lower lid margin staining compared with that of the nonwearers regardless of the symptom status. This work provides further insight into the interaction between the marginal conjunctiva and the contact lens surface and adds to the growing body of evidence linking the marginal conjunctiva and contact lens comfort.
REFERENCES 1. Richdale K, Sinnott LT, Skadahl EBS, et al. Frequency of and factors associated with contact lens dissatisfaction and discontinuation. Cornea. 2007;26:168–174. 2. Dumbleton K, Woods CA, Jones LW, et al. The impact of contemporary contact lenses on contact lens discontinuation. Eye Contact Lens. 2013; 39:93–99.
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3. Nichols KK, Redfern RL, Jacob JT, et al. The TFOS International Workshop on Contact Lens Discomfort: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2013;54: TFOS14–TFOS19. 4. Jones L, Brennan NA, Gonzalez-Meijome J, et al. The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens materials, design, and care subcommittee. Invest Ophthalmol Vis Sci. 2013;54:TFOS37–TFOS70. 5. Craig JP, Willcox MD, Argueso P, et al. The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the tear film subcommittee. Invest Ophthalmol Vis Sci. 2013;54:TFOS123–TFOS156. 6. Allansmith MR, Korb DR, Greiner JV, et al. Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol. 1977;83:697–708. 7. Nichols JJ, Willcox MDP, Bron AJ, et al. The TFOS International Workshop on Contact Lens Discomfort: executive summary. Invest Ophthalmol Vis Sci. 2013;54:TFOS7–TFOS13. 8. Chalmers R. Overview of factors that affect comfort with modern soft contact lenses. Contact Lens and Anterior Eye. 2014;37:65–76. 9. Knop E, Knop N, Zhivov A, et al. The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: an in vivo confocal and histological study. J Anat. 2011;218:449–461. 10. Korb DR, Greiner JV, Herman JP, et al. Lid-wiper epitheliopathy and dry-eye symptoms in contact lens wearers. CLAO J. 2002;28:211–216. 11. Yeniad B, Beginoglu M, Bilgin LK. Lid-wiper epitheliopathy in contact lens users and patients with dry eye. Eye Contact Lens. 2010;36: 140–143. 12. Berry M, Pult H, Purslow C, et al. Mucins and ocular signs in symptomatic and asymptomatic contact lens wear. Optom Vis Sci. 2008;85:E930–E938. 13. Pult H, Purslow C, Berry M, et al. Clinical tests for successful contact lens wear: relationship and predictive potential. Optom Vis Sci. 2008;85: E924–E929. 14. Jalbert I, Madigan MC, Shao M, et al. Assessing the human lid margin epithelium using impression cytology. Acta Ophthalmol. 2012;90: e547–e552. 15. Toker E, Asfuroglu E. Corneal and conjunctival sensitivity in patients with dry eye: the effect of topical cyclosporine therapy. Cornea. 2010;29: 133–140. 16. Golebiowski B, Chim K, So J, et al. Lid margins: sensitivity, staining, meibomian gland dysfunction, and symptoms. Optom Vis Sci. 2012;89: e1443–e1449.
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17. Du Toit R, Vega JA, Fonn D, et al. Diurnal variation of corneal sensitivity and thickness. Cornea. 2003;22:205–209. 18. Chalmers RL, Begley CG, Moody K, et al. Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance. Optom Vis Sci. 2012;89:1435–1442. 19. Young G, Chalmers R, Napier L, et al. Soft contact lens-related dryness with and without clinical signs. Optom Vis Sci. 2012;89:1125–1132. 20. Hughes C, Hamilton L, Doughty MJ. A quantitative assessment of the location and width of Marx’s line along the marginal zone of the human eyelid. Optom Vis Sci. 2003;80:564–572. 21. Navascues-Cornago M, Maldonado-Codina C, Morgan PB. Mechanical sensitivity of the human conjunctiva. Cornea. 2014;33:855–859. 22. Maldonado-Codina C, Morgan PB, Efron N, et al. Comparative clinical performance of rigid versus soft hyper Dk contact lenses used for continuous wear. Optom Vis Sci. 2005;82:536–548. 23. Bentivoglio AR, Bressman SB, Cassetta E, et al. Analysis of blink rate patterns in normal subjects. Mov Disord. 1997;12:1028–1034. 24. Doane MG. Interactions of eyelids and tears in corneal wetting and the dynamics of the normal human eyeblink. Am J Ophthalmol. 1980;89:507–516. 25. Murphy PJ, Lawrenson JG, Patel S, et al. Reliability of the non-contact corneal aesthesiometer and its comparison with the Cochet-Bonnet aesthesiometer. Ophthalmic Physiol Opt. 1998;18:532–539. 26. Golebiowski B, Papas EB, Stapleton F. Assessing the sensory function of the ocular surface: implications of use of a non-contact air jet aesthesiometer versus the Cochet-Bonnet aesthesiometer. Exp Eye Res. 2011;92:408–413. 27. Golebiowski B, Lim M, Papas E, et al. Understanding the stimulus of an air-jet aesthesiometer: computerised modelling and subjective interpretation. Ophthalmic Physiol Opt. 2013;33:104–113. 28. McGowan DP, Lawrenson JG, Ruskell GL. Touch sensitivity of the eyelid margin and palpebral conjunctiva. Acta Ophthalmol (Copenh). 1994;72:57–60. 29. Norn MS. Conjunctival sensitivity in normal eyes. Acta Ophthalmol. 1973;51:58–66. 30. Munger BL, Halata Z. The sensorineural apparatus of the human eyelid. Am J Anat. 1984;170:181–204. 31. Millodot M. Diurnal variation of corneal sensitivity. Br J Ophthalmol. 1972;56:844–847.
32. Millodot M, Henson DB, O’Leary DJ. Measurement of corneal sensitivity and thickness with PMMA and gas-permeable contact lenses. Am J Optom Physiol Opt. 1979;56:628–632. 33. Douthwaite WA, Connelly AT. The effect of hard and gas permeable contact lenses on refractive error, corneal curvature, thickness and sensitivity. J Br Contact Lens Assoc. 1986;9:14–20. 34. Sanaty M, Temel A. Corneal sensitivity changes in long-term wearing of hard polymethylmethacrylate contact lenses. Ophthalmologica. 1998; 212:328–330. 35. Velasco MJ, Bermudez FJ, Romero J, et al. Variations in corneal sensitivity with hydrogel contact lenses. Acta Ophthalmol (Copenh). 1994;72:53–56. 36. Millodot M. Effect of soft lenses on corneal sensitivity. Acta Ophthalmol (Copenh). 1974;52:603–608. 37. Larke JR, Hirji NK. Some clinically observed phenomena in extended contact lens wear. Br J Ophthalmol. 1979;63:475–477. 38. Lowther GE, Hill RM. Sensitivity threshold of the lower lid margin in the course of adaptation to contact lenses. Am J Optom Arch Am Acad Optom. 1968;45:587–594. 39. Abelson MB, Greiner JV, Chan-Ling T, et al. Adaptive changes in the threshold sensitivity of the tarsus as measured with Cochet-Bonnet aesthesiometer. Invest Ophthalmol Vis Sci. 1993;34:s1006. Abstract. 40. Lum E, Golebiowski B, Gunn R, et al. Corneal sensitivity with contact lenses of different mechanical properties. Optom Vis Sci. 2013;90: 954–960. 41. Situ P, Simpson TL, Jones LW, et al. Effects of silicone hydrogel contact lens wear on ocular surface sensitivity to tactile, pneumatic mechanical, and chemical stimulation. Invest Ophthalmol Vis Sci. 2010;51: 6111–6117. 42. Kessing SV. A new division of the conjunctiva on the basis of x-ray examination. Acta Ophthalmol (Copenh). 1967;45:680–683. 43. Golebiowski B, Papas E, Begley C, et al. Ocular surface sensitivity and symptoms in contact lens wear: Proceedings of the Fifth International Conference on the Tear Film and Ocular Surface: Basic Science and Clinical Relevance. Taormina, Sicily, Italy, September 5–8, 2007;68. 44. Chen J, Simpson TL. A Role of corneal mechanical adaptation in contact lens–related dry eye symptoms. Invest Ophthalmol Vis Sci. 2011;52: 1200–1205.
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Lid Margin Sensitivity and Staining in Contact Lens Wear Versus No Lens Wear Maria Navascues-Cornago, BSc, MSc, Philip B. Morgan, BSc, PhD, MCOptom, FAAO, and Carole Maldonado-Codina, MSc, PhD, MCOptom, FAAO
Purpose: To map the sensitivity and staining of the marginal conjunctiva in soft contact lens (SCL) wearers and nonwearers and to investigate diurnal changes.
Methods: Thirty-five nonwearers and 35 SCL wearers were recruited. Mechanical sensitivity was measured at 8 locations on the ocular surface and adnexa (cornea, marginal, bulbar, and tarsal conjunctivae) using the Cochet–Bonnet aesthesiometer. Lid margin staining (lissamine green) was assessed through image analysis. Measurements were repeated at 12 hours in 11 nonwearers and 10 symptomatic SCL wearers. Results: The marginal conjunctiva was the most sensitive conjunctival region (all P , 0.001). There was no significant difference in sensitivity at 12 hours (all P . 0.05). There was a significant difference in sensitivity between the 2 groups in the morning for the lower lid tarsal conjunctiva (P = 0.003). After 12 hours, the sensitivity of the lower lid marginal conjunctiva was found to be reduced in SCL wearers compared with nonwearers (all P , 0.05). Lower lid margin staining was greater than upper lid margin staining in both groups (all P , 0.05). In the SCL wearers, a significant increase in lower lid margin staining was found at 12 hours compared with the morning (P = 0.04). After 12 hours, lower lid margin staining was significantly greater in SCL wearers compared with nonwearers (P = 0.03).
Conclusions: This work has demonstrated that the marginal conjunctiva is the most sensitive conjunctival region. After 12 hours, symptomatic lens wearers showed decreased sensitivity of the lower marginal conjunctiva and increased lower lid margin lissamine green staining compared with those of the nonwearers. Key Words: marginal conjunctiva, ocular surface sensitivity, contact lenses, Cochet-Bonnet aesthesiometer, lid margin staining (Cornea 2015;34:808–816)
Received for publication September 23, 2014; revision received February 24, 2015; accepted February 28, 2015. Published online ahead of print May 1, 2015. From Eurolens Research, Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom. This work forms part of a self-funded PhD program of research. The authors have no funding or conflicts of interest to disclose. Reprints: Maria Navascues-Cornago, BSc, MSc, Eurolens Research, Carys Bannister building, The University of Manchester, Dover St, Manchester M13 9PL, United Kingdom (e-mail: maria.navascuescornago@manchester. ac.uk). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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ontact lens discomfort (CLD) is the primary reason for discontinuation from contact lens wear.1,2 CLD is characterized by a series of adverse sensations related to lens wear that may lead to decreased comfortable wearing hours, a reduction in total wearing time and discontinuation from lens wear.3 Many factors have been related to CLD, such as lens modulus, surface properties, design and fit, care system,4 tear film characteristics,5 and contact lens–related pathology such as giant papillary conjunctivitis.6 Comprehensive recent reviews of this area have been provided by the TFOS International Workshop on Contact Lens Discomfort7 and Chalmers.8 Despite this extensive research base and major reviews of the field, the etiology of CLD still remains unclear. One CLD factor that has recently received attention is the lid margin and its interaction with the contact lens surface. The lid margin is divided into 3 distinct anatomical subzones: the skin epidermis extending over the meibomian gland orifices, the mucocutaneous junction (transition region between the skin epidermis and the conjunctival tissue, the surface that represents the line of Marx), and the marginal conjunctiva, also known as the “lid wiper.” The marginal conjunctiva is a prominent epithelial thickening of the inner lid border that gradually decreases toward the subtarsal fold. The marginal conjunctiva is believed to be the only region of the lid margin that is apposed to the globe and to be responsible for the spread of the tear film over the ocular surface (or lens surface) during blinking.9 Staining of the lid margin has been associated with symptoms of discomfort and dryness in soft contact lens (SCL) wearers and in patients with dry eye.10–13 There is no strong evidence of greater lid margin staining in SCL wearers than in nonwearers.11,14 Although the etiology of lid margin staining remains unclear, it has been hypothesized that it may result from increased frictional forces between the lid margin and the ocular or lens surface during blinking when the lubrication is inadequate.10,12,13 Although a correlation between corneal and conjunctival sensitivity and staining of the ocular surface has been reported in patients with dry eye,15 previous studies investigating the relationship between lid margin staining and sensitivity in healthy subjects without contact lenses were unable to find any association.16 Furthermore, the relationship between lid margin staining and conjunctival mechanical thresholds has not been fully investigated in SCL wearers. The purpose of this work was to map the sensitivity of the marginal and tarsal conjunctivae of the upper and lower eyelids and bulbar conjunctival regions in SCL wearers and Cornea Volume 34, Number 7, July 2015
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Cornea Volume 34, Number 7, July 2015
nonwearers and to investigate whether the sensitivity of these areas changed over a 12-hour period. Lid margin staining and its relationship with sensitivity of the marginal conjunctiva were determined.
METHODS Study Design This study was randomized, controlled, and subject masked. Ethical approval for performing this work was obtained from the University of Manchester Committee on the Ethics of Research on Human Beings. The study was conducted in accordance with the tenets of the Declaration of Helsinki. All subjects were given information about the study before they signed a consent form to participate.
Subjects To determine the study sample size, power analysis was performed using data from a previous pilot investigation. If 33 subjects completed the study, the study would have 80% power to detect a 1-cm difference in sensitivity using a Cochet–Bonnet aesthesiometer, assuming an alpha of 0.05, a 2-tailed paired analysis, and an SD of differences 2.0. To allow for subject discontinuations, 35 nonwearers and 35 SCL wearers were recruited for the morning visit. If 10 subjects completed the end-of-day visit, the study would have 80% power to detect a 1-cm difference in sensitivity over the course of the day, assuming an alpha of 0.05, a 2-tailed paired analysis, and an SD of differences 1.0. The exclusion criteria were any systemic or ocular disorder that may affect ocular health, grade 2 or greater of any anterior ocular clinical signs, use of any topical medication such as eye drops or ointment, previous cataract or corneal refractive surgery, and being pregnant or lactating. Nonwearers should never have previously worn contact lenses for more than 2 weeks. Contact lens wearers must be wearing SCLs on a daily wear basis (a minimum of 8 hours per day, 5 days per week) for a period of at least 6 months.
Experimental Protocol All subjects attended a morning visit, and a subset was asked to attend an end-of-day visit. The first 11 nonwearers and 10 symptomatic SCL wearers who satisfied the inclusion criteria and were willing to participate in the second visit at 12 hours were selected. At the morning visit, all measurements were taken at least 2 hours after waking to minimize any issues related to overnight corneal edema.17 Contact lens wearers were asked to attend this visit without any lenses in situ (and not having worn lenses beforehand on the day). Details of the ocular history were recorded, and an anterior eye examination was undertaken. Only SCL wearers completed the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8)18 and were classified as either asymptomatic or symptomatic by the criteria set by Young et al.19 Briefly, subjects were classified as symptomatic or asymptomatic based on their responses to frequency Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Lid Margin Sensitivity and Staining
and intensity of dryness symptoms. Eighteen subjects were classified as symptomatic SCL wearers. The overall subjective comfort for their habitual contact lenses was recorded using an annotated vertical analog grading scale where 0 represented “cannot be tolerated” and 100 represented “cannot be felt.” Lid margin staining was assessed using lissamine green strips (GreenGlo; Hub Pharmaceuticals LLC, Rancho Cucamonga, CA) soaked for 1 minute in 0.9% sterile saline (Eye Care solutions; Crest Medical Ltd, Warrington, United Kingdom) and applied to the conjunctival sac. Four minutes from the first instillation, the same procedure was repeated. One minute from the last instillation, images of the lissamine green staining of the upper and the lower eyelid were taken with a slit lamp (SL-D4; Topcon, Tokyo, Japan), under white light, using ·10 magnification, and a slit-lamp beam width of approximately 14 mm. The area of lissamine green staining was recorded by analyzing digital images of the right eye using ImageJ (V.1.46; National Institutes of Health, USA, http://rsbweb.nih.gov/ij/). The lid margin staining area was defined as the area of lissamine green staining that extended from the lacrimal punctum to the temporal canthus and from the line of Marx to the subtarsal fold.10 The area of the line of Marx, which is represented as a thin line of lissamine green staining (0.1 6 0.1 mm)20 visible in most healthy eyes, was included in the measurement of the lid margin staining area. For the upper lid examination, the upper eyelid was everted, always being careful not to contact the area of the lid margin staining. Mechanical thresholds of the ocular surface were measured using a Cochet–Bonnet aesthesiometer (Luneau Ophtalmologie, Paris, France) with a 0.1 mm-diameter nylon filament. The Cochet–Bonnet aesthesiometer was mounted on a slit lamp to allow accurate application of the stimulus with the aid of the magnification observation system, which ensured that the filament approached the ocular surface smoothly and perpendicularly. Calibration and mechanical thresholds were determined using the ascending method of limits, which has been described in a previous study.21 Four stimuli were presented at each filament length, and the length that gave 2 or more positive responses was taken to be the mechanical threshold. Mechanical thresholds were determined at the following locations: central cornea, temporal bulbar conjunctiva (approximately 3 mm from the limbus), upper and lower marginal conjunctivae (central and temporal approximately 5 mm from the center), and upper and lower tarsal conjunctivae (approximately 2 mm posterior to the line of Marx). Because the measurement of the sensitivity using the Cochet–Bonnet aesthesiometer is a time-consuming procedure for subjects, the sensitivity was only determined at temporal locations (and not at nasal locations), and this was considered representative of the off-center sensitivity. The order of assessment of each of these locations was randomized. Complete eversion of the upper eyelid and partial eversion of the lower eyelid were required to measure the sensitivity of the marginal and tarsal conjunctivae. The exact location of the sensitivity measurement for the marginal conjunctiva depended on whether there was www.corneajrnl.com |
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lissamine green staining of the lid margin. When the lid margin displayed an area of staining, the sensitivity was measured in the middle of the staining (in a vertical direction). If only the line of Marx was stained, the sensitivity was measured approximately 0.1 mm posterior to the line of Marx. An eyepiece graticule (Eyepiece BM 10·; Haag-Streit AG, Koeniz, Switzerland) was used at ·10 magnification to perform these measurements accurately. At the end of the visit, when all clinical measurements were completed, a subgroup of 10 symptomatic SCL wearers used their own contact lenses and wore them for 12 hours during which time they conducted their normal daily routine. Comfort scores were recorded once their contact lenses were worn. Repeated measurements were taken at 12 hours in these subjects and in a further subgroup of 11 nonwearers. Subjective lens comfort was assessed at the start of this end-of-day visit using the 100-point vertical analog scale. Lens fit was assessed by horizontal and vertical centration, movement (in primary gaze after a blink), and corneal coverage.22 Contact lenses were then removed (if applicable), and measurements were immediately repeated for sensitivity and lid margin staining as occurred at the morning visit. All measurements were taken at normal conditions of temperature (range, 18.6– 24.7°C) and relative humidity (range, 30%–54.8%).
TABLE 1. Post Hoc Power Analysis SD Alpha Difference, cm Power Differences in sensitivity between locations Diurnal differences in sensitivity
Nonwearers SCL wearers Nonwearers SCL wearers
1.2 1.4
0.05 0.05
1 1
0.9986 0.9862
0.6 1.1
0.05 0.05
1 1
0.9986 0.7566
and overall lens comfort scores were significantly negatively correlated (Spearman r = 20.58, P , 0.001). There was a decrease in subjective comfort after 12 hours of lens wear in the subgroup of symptomatic SCL wearers (92.8 6 7.8 vs. 68.3 6 15.6, Wilcoxon signed-rank test, P = 0.005). Lens-fitting characteristics after 12 hours of lens wear were optimum to slightly inadequate (centration 0.0 6 0.2; coverage 0.2 6 0.1; and movement 0.1 6 0.1). Clinical measurements were taken in the morning in all subjects. Measurements were repeated at 12 hours in a subgroup of 11 nonwearers (6 women and 5 men; mean age: 28.9 6 9.9 years, range: 22–57 years) and 10 symptomatic SCL wearers (5 women and 5 men; mean age: 26.5 6 7.9 years, range: 20–40 years).
Statistical Analysis
Lid Margin Staining
Only data for the right eye were included in the analyses. Statistical analyses were performed using SPSS Statistic version 20 (IBM Corp, Armonk, NY). The Shapiro–Wilk test showed that variables were not normally distributed, and therefore, nonparametric analysis was performed. The Friedman test was used to analyze sensitivity data at the various ocular locations. Any significant difference was further investigated using the Wilcoxon signed-rank test. Differences in sensitivity at 12 hours and lid margin staining were also analyzed using the Wilcoxon signed-rank test. The Mann–Whitney U test was used to analyze differences in variables between nonwearers and SCL wearers. Correlation between variables was analyzed using Spearman rank correlation coefficients. P , 0.05 was considered statistically significant. Bonferroni correction was used to adjust the level of significance when multiple comparisons were performed to avoid type 1 errors.
Thirty-five nonwearers and 35 SCL wearers were enrolled in the study. Post hoc power analysis was calculated using the typical SD observed in the present data and assuming a 2-tailed analysis and an alpha of 0.05 (Table 1). Demographic details of subjects are shown in Table 2. There were no significant differences in demographics between nonwearers and SCL wearers (all P . 0.05) or between symptomatic and asymptomatic SCL wearers (all P . 0.05). As expected, CLDEQ-8 scores were higher for the symptomatic group compared with the asymptomatic group (unpaired t test, P , 0.001), and there was a significant difference in overall lens comfort between the 2 groups (Mann–Whitney U test, P , 0.001). CLDEQ-8 scores
Digital images that were not considered clear enough to be analyzed with ImageJ were discarded. Therefore, in the nonwearers, the number of images analyzed was as follows: 34 images of the upper eyelid and 34 images of the lower eyelid from the morning visit; and 10 images of the upper eyelid and 11 images of the lower eyelid at the end-of-day visit. All pictures were considered suitable for analysis in the SCL wearers. Figure 1 shows the area of lid margin staining for the nonwearers and SCL wearers in the morning. Lid margin staining was significantly greater for the lower eyelid compared with that of the upper eyelid in the morning for both groups (Wilcoxon signed-rank test, nonwearers, P = 0.002, SCL wearers, P = 0.001) and at the end of the day only for the nonwearers (Wilcoxon signed-rank test, P = 0.005). A comparison of lid margin staining between the morning and the end of the day is represented in Figure 2. In the nonwearers, no significant change was found in lid margin staining over 12 hours (Wilcoxon signed-rank test, all P . 0.05). In the SCL wearers, a significant increase was found at 12 hours only for the lower eyelid (Wilcoxon signed-rank test, P = 0.04). The staining of the upper and lower eyelids was marginally correlated in the nonwearers (Spearman r = 0.33, P = 0.06), and it was positively correlated in the SCL wearers (Spearman r = 0.55, P = 0.001). There was no correlation between lid margin staining and CLDEQ-8 and/or lens comfort scores (Spearman, all P . 0.05). Lid margin staining was not significantly different between symptomatic and asymptomatic SCL wearers (Mann–Whitney U test, all P . 0.05) (Fig. 3).
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Lid Margin Sensitivity and Staining
TABLE 2. Demographic Details of Subjects Attending the Morning Visit Nonwearers (n = 35)
All SCL Wearers (n = 35)
Age (mean 6 SD), yr Gender CL experience (mean 6 SD), yr CL material CL design CL replacement frequency
27.7 6 7.3 20 F, 15 M NA NA NA NA
CLDEQ-8 score (mean 6 SD) Overall lens comfort score (mean 6 SD)
NA NA
25.6 6 7.4 21 F, 14 M 7.4 6 7.1 23 H, 12 SH 29 sphere, 6 toric 18 daily, 14 monthly, 2 bi-weekly, 1 yearly 11.7 6 5.4 80.9 6 15.1
P
Symptomatic SCL Wearers (n = 18)
0.24 25.0 6 6.5 0.81 10 F, 8 M NA 5.7 6 5.6 NA 13 H, 5 SH NA 15 sphere, 3 toric NA 10 daily, 7 monthly, 1 yearly NA NA
15.4 6 3.7 73.0 6 16.4
Asymptomatic SCL Wearers (n = 17) 26.2 6 8.4 11 F, 6 M 9.3 6 8.1 10 H, 7 SH 14 sphere, 3 toric 8 daily, 7 monthly, 2 bi-weekly 7.8 6 4.1 89.2 6 7.3
P 0.62 0.58 0.1 0.4 1 0.76 ,0.001 ,0.001
Bold values indicate a significant difference, P , 0.05. CL, contact lens.
Lid margin staining was not significantly different between nonwearers and SCL wearers in the morning (Mann–Whitney U test, all P . 0.05) (Fig. 1). Twelve hours later, there was no significant difference in lid margin staining between the 2 groups for the upper lid (Mann–Whitney U test, P = 0.08), but the staining of the lower lid was significantly greater in the SCL wearers compared with the nonwearers (Mann–Whitney U test, P = 0.03) (Fig. 2).
Sensitivity Thresholds Table 3 shows mechanical thresholds for the various stimulus locations in the morning and at the end of the day.
There was a significant difference in sensitivity between the various ocular locations in both groups (Friedman, all P , 0.001). In both groups, the cornea was the most sensitive region (Wilcoxon signed-rank test, P , 0.001). The marginal conjunctiva was more sensitive than the bulbar and tarsal conjunctivae (Wilcoxon signed-rank test, P , 0.001). The temporal marginal conjunctiva was more sensitive than the central marginal conjunctiva in nonwearers (Wilcoxon signed-rank test, P , 0.05). The upper tarsal conjunctiva was more sensitive than the lower tarsal conjunctiva in both groups (Wilcoxon signed-rank test, P , 0.05). There was a significant difference in sensitivity between the 2 groups in the morning for the tarsal
FIGURE 1. Box and whisker plots comparing lid margin staining between nonwearers (n = 34) and SCL wearers (n = 35) in the morning. The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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FIGURE 2. Box and whisker plots comparing lid margin staining in the morning and at the end of the day in nonwearers (n = 10) and symptomatic SCL wearers (n = 10). The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range.
conjunctiva of the lower eyelid (Mann–Whitney U test, Bonferroni-adjusted P , 0.006). Mechanical thresholds measured at the end of the day are compared with those in the morning in Table 4. No significant difference in sensitivity was found between the morning and the end of the day for any of the locations (Wilcoxon signed-rank test, Bonferroni-adjusted, all P . 0.006) within each. After 12 hours, sensitivity of the lower lid marginal conjunctiva was found to be reduced in the SCL wearers compared with the nonwearers (Mann–Whitney U test, Bonferroni-adjusted, all P , 0.006). Mechanical thresholds were not significantly different between asymptomatic and symptomatic SCL wearers at the morning visit (Mann–Whitney U test, Bonferroni-adjusted, all P . 0.006) and were not correlated with CLDEQ-8 and/or comfort scores (Spearman, all P . 0.05). At the end of the day, the mechanical threshold of the temporal marginal conjunctiva of the lower eyelid was negatively correlated with lid margin staining only in the nonwearers (Spearman r = 20.683, P = 0.03).
This study investigated the sensitivity of the cornea and conjunctiva at different locations and compared them across a 12-hour period and between groups of SCL wearers and nonwearers. Lid margin staining and its relationship with sensitivity of the marginal conjunctiva were also determined.
Lid margin staining assessed in the morning was greater for the lower eyelid compared with that of the upper eyelid in both nonwearers and SCL wearers, which has been previously reported in nonwearers.16 Although lid margin staining was similar between SCL wearers and nonwearers in the morning, the staining of the lower lid margin was significantly greater in the symptomatic SCL wearers compared with the nonwearers at the end of the day. Lid margin staining of the upper eyelid is believed to be induced by mechanical microtrauma of the marginal conjunctiva during blinking resulting from inadequate lubrication between the lid margin and the ocular surface.10,12,13 It is reasonable to expect the upper eyelid to display increased staining at the end of the day compared with that at the morning as a result of thousands of daily blinks.23 However, the staining of the upper lid margin did not show a significant diurnal change in this study (for either group), whereas the staining of the lower lid increased at the end of the day in symptomatic SCL wearers. This finding supports the hypothesis that the mechanism for staining of the upper lid margin may be different from that for the lower lid. Indeed, lid margin staining may not be produced as a result of microtrauma. Previous studies have hypothesized that lower lid margin staining may be caused by chemical injury as a result of the pooling of tears in the lower meniscus leading to a longer interaction with the dye and/or to longer exposure to inflammatory mediators of tears,16 although this has not been demonstrated yet. Additionally, the lower eyelid also moves during blinking24 and it is still unknown how this
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DISCUSSION
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Cornea Volume 34, Number 7, July 2015
Lid Margin Sensitivity and Staining
FIGURE 3. Box and whisker plots comparing lid margin staining in the morning between asymptomatic (n = 17) and symptomatic (n = 18) SCL wearers. The boxes extend from the 25th to 75th percentiles. The median is represented by a horizontal line within the box. The whiskers represent minimum and maximum values within the 1.5 interquartile range (IQR); the points indicate outliers between 1.5 and 3 IQR and the asterisks indicate data points beyond this range.
predominantly horizontal movement and its interaction with the contact lens could affect the integrity of the lid margin. Although lid margin staining was numerically greater in the symptomatic SCL wearers compared with the asymptomatic SCL wearers at the morning visit, this difference was not statistically significant. Although staining of the upper lid margin has been consistently associated with symptoms of dryness in SCL wearers,10,11,13 previous investigations have failed to demonstrate such an association for the staining of the lower eyelid.12,13 Differences among studies may be due to disparities in the methodology, that is, the vital dye(s) used and the grading method. Post hoc power analysis for 3 of the 4 variables suggests that the study comfortably held sufficient statistical power for meaningful differences to be detected. For the fourth variable—the diurnal change in sensitivity for the SCL wearers—the calculated power was just below the normal threshold adopted in clinical studies at 0.8. This value may also overestimate statistical power because our power calculations are based on parametric methods and nonparametric approaches were used in our analysis. As such, caution needs to be applied in drawing a conclusion on diurnal sensitivity for this group. A limitation of the Cochet–Bonnet aesthesiometer that may have affected the results of this study is its truncated stimulus intensity range. Previous studies have shown that corneal thresholds in some subjects may be outside the stimulus intensity range delivered by the 0.1-mm-diameter filament, which results in an underestimation of corneal Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
sensitivity.25,26 In this study, thresholds in the morning were at the measurable limit of the filament in 82.9% of nonwearers and 85.7% of SCL wearers for the cornea and 20% to 51.4% of nonwearers and 17.1% to 37.1% of SCL wearers for the marginal conjunctiva. For the subgroup of nonwearers and SCL wearers, thresholds in the morning were at the maximum filament length in 100% and 80% of subjects, respectively, for the cornea and 18.2% to 63.6% and 30% to 50% of subjects, respectively, for the marginal conjunctiva. The large proportion of subjects who had thresholds at the limit of detection may have affected the ability to determine differences in sensitivity between groups and between time points for the most sensitive ocular regions (ie, the cornea and marginal conjunctiva). However, those differences that are reported to be statistically significant can be considered to be real. Despite this limitation, this instrument was considered the most suitable to assess the sensitivity in this study because it was necessary to stimulate very specific ocular regions (particularly the marginal conjunctiva), which only could be achieved using this device. Although the noncontact corneal aesthesiometer may be able to measure at levels below the limits of the Cochet–Bonnet aesthesiometer,25,26 the size and location of the stimulated area is not completely defined.27 In line with previous investigations, the marginal conjunctiva was more sensitive than the bulbar and tarsal conjunctivae.28,29 Morphological studies investigating the sensory innervation of the human eyelid revealed a greater density of nerve endings present in the lid margin area,30 which may explain the increased sensitivity of the marginal www.corneajrnl.com |
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Cornea Volume 34, Number 7, July 2015
Navascues-Cornago et al
TABLE 3. Comparison of Median (Interquartile Range) Mechanical Thresholds Between Nonwearers and SCL Wearers in the Morning (n = 35 vs. n = 35) and at the End of Day (n = 11 vs. n = 10) Stimulus Location Cornea
Bulbar conjunctiva
Upper lid central marginal conjunctiva Upper lid temporal marginal conjunctiva Lower lid central marginal conjunctiva Lower lid temporal marginal conjunctiva Upper lid tarsal conjunctiva
Lower lid tarsal conjunctiva
Time Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day Morning End of the day
Nonwearers, mN
% of Thresholds at the Limit (ie, 6 cm)
SCL Wearers, mN
% of Thresholds at the Limit (ie, 6 cm)
P
0.2 (0.2–0.2) 0.2 (0.2–0.2)
82.9 100
0.2 (0.2–0.2) 0.2 (0.2–0.3)
85.7 70
0.85 0.06
1.2 (0.9–1.9) 0.7 (0.4–1.8)
0 9.1
1.2 (0.7–8.7) 1.0 (0.4–10.6)
2.9 10
0.69 0.62
0.4 (0.2–0.5) 0.2 (0.2–0.3)
25.7 63.6
0.3 (0.2–0.5) 0.3 (0.2–0.5)
37.1 30
0.84 0.1
0.2 (0.2–0.4) 0.2 (0.2–0.3)
51.4 54.5
0.4 (0.2–0.5) 0.3 (0.2–0.6)
34.3 40
0.07 0.35
0.4 (0.3–0.4) 0.2 (0.2–0.3)
20 54.5
0.3 (0.3–0.5) 0.6 (0.4–0.9)
17.1 10
0.95 0.005
0.3 (0.2–0.4) 0.2 (0.2–0.2)
31.4 81.8
0.3 (0.2–0.5) 0.5 (0.3–0.8)
37.1 20
0.56 0.003
0.9 (0.5–1.8) 0.5 (0.4–0.9)
0 0
1.8 (0.7–8.7) 2.4 (0.7–10.6)
5.7 20
0.06 0.08
1.8 (0.7–3.6) 0.9 (0.4–8.7)
2.9 9.1
8.7 (1.8–16.3) 5.3 (0.4–18.5)
2.9 0
0.003 0.32
Bold values indicate a significant difference, Bonferroni-adjusted P , 0.006.
conjunctiva compared with that of the tarsal conjunctiva. In this study, no significant change was found in the ocular surface sensitivity after a 12-hour period in nonwearers. This is contrary to previous studies that have shown an increase in corneal sensitivity throughout the day.17,31 One fact that may explain these differences is that greater changes in corneal sensitivity may occur on eye opening upon awakening,17,31 but in this study, to minimize the effect of overnight corneal swelling on sensitivity measurements, thresholds were measured at least 2 hours after the subjects awoke.17 The wear of contact lenses over a 12-hour period had no significant impact on mechanical thresholds of the ocular surface in the symptomatic subjects. In addition, the sensitivity measured in the morning was similar between nonwearers and SCL wearers for most of the regions, except for the inferior tarsal conjunctiva, which was less sensitive in the SCL wearers. Previous studies using the Cochet–Bonnet aesthesiometer have shown decreased corneal sensitivity after short-term and long-term wear of rigid gas-permeable,32,33 poly-methyl methacrylate (PMMA),32–34 and conventional hydrogel contact lenses.35–37 Reduced sensitivity of the tarsal conjunctiva and lid margin with rigid gas-permeable, PMMA, and conventional hydrogel contact lenses has also been reported.38,39 For silicone hydrogel lenses, previous studies have shown either no change40 or a decrease41 in corneal sensitivity, whereas no change has been reported for the sensitivity of the bulbar conjunctiva.41 The exact mechanism responsible for changes in the ocular surface sensitivity as
a result of contact lens wear is unclear. Sensory changes have been attributed to metabolic disorders caused by lens-induced hypoxia,32,35 neural adaptation to mechanical stimulation,32,41 and neural sensitization in response to inflammation or hyperosmolarity.41 Studies based on x-ray examinations have shown that only the lid margin of the upper eyelid is directly in contact with the ocular surface, whereas the entire tarsal area of the lower eyelid is in close apposition with the globe.42 The interaction between the lens and the tarsal area could have affected the sensitivity of this area. Nonetheless, the difference in sensitivity of the inferior tarsal conjunctiva between SCL wearers and nonwearers was only significant during the morning. Considering that recovery of sensitivity may occur within a few hours after stopping lens wear35,36 and the fact that all lenses were used on a daily wear basis, it is perhaps not unexpected to have found no difference in sensitivity between SCL wearers and nonwearers in the morning. The reduced sensitivity of the lower lid marginal conjunctiva found in SCL wearers compared with nonwearers at the end of the day is a surprising finding considering that such a difference was not found for the upper lid marginal conjunctiva. If we consider a mechanical etiology for the reduction in sensitivity, it would be expected that the upper lid marginal conjunctiva was more affected given its continuous interaction with the lens surface during blinking. However, the movement of the lower eyelid and its interaction with the lens surface could affect the sensitivity of the
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Lid Margin Sensitivity and Staining
TABLE 4. Comparison of Median (Interquartile Range) Mechanical Thresholds in the Morning and at the End of Day for Nonwearers (n = 11) and SCL Wearers (n = 10) Location
Group
Cornea
Morning, mN
Nonwearers 0.2 SCL wearers 0.2 Bulbar conjunctiva Nonwearers 0.9 SCL wearers 0.6 Upper lid central marginal conjunctiva Nonwearers 0.3 SCL wearers 0.3 Upper lid temporal marginal conjunctiva Nonwearers 0.2 SCL wearers 0.3 Lower lid central marginal conjunctiva Nonwearers 0.2 SCL wearers 0.3 Lower lid temporal marginal conjunctiva Nonwearers 0.3 SCL wearers 0.3 Upper lid tarsal conjunctiva Nonwearers 0.7 SCL wearers 1.5 Lower lid tarsal conjunctiva Nonwearers 0.9 SCL wearers 12.5
% of Thresholds at Limit % of Thresholds at Limit (ie, 6 cm) End of the Day, mN (ie, 6 cm)
(0.2–0.2) (0.2–0.3) (0.7–1.2) (0.4–4.8) (0.3–0.4) (0.2–0.5) (0.2–0.4) (0.2–0.5) (0.2–0.4) (0.2–0.5) (0.2–0.3) (0.2–0.6) (0.7–1.2) (0.5–16.3) (0.7–1.8) (0.4–16.3)
100 80 0 10 18.2 50 63.6 50 54.5 30 45.5 50 0 10 9.1 10
0.2 0.2 0.7 1.0 0.2 0.3 0.2 0.3 0.2 0.6 0.2 0.5 0.5 2.4 0.9 5.3
(0.2–0.2) (0.2–0.3) (0.4–1.8) (0.4–10.6) (0.2–0.3) (0.2–0.5) (0.2–0.3) (0.2–0.6) (0.2–0.3) (0.4–0.9) (0.2–0.2) (0.3–0.8) (0.4–0.9) (0.7–10.6) (0.4–8.7) (0.4–18.5)
100 70 9.1 10 63.6 30 54.5 40 54.5 10 81.2 20 0 20 9.1 0
P 1 1 0.67 0.31 0.01 0.25 0.79 0.42 0.75 0.01 0.18 0.18 0.07 0.16 0.78 0.88
Bold values indicate a significant difference, Bonferroni-adjusted P , 0.006.
lower lid margin. Further research is needed to understand the exact mechanism for sensory changes related to lens wear. The relationship between discomfort symptoms reported by contact lens wearers and changes in the sensitivity of the ocular surface is poorly understood. Symptomatic and asymptomatic SCL wearers showed similar mechanical thresholds. Investigations using the noncontact corneal aesthesiometer have also reported no clear association between symptoms and ocular sensitivity.43 A more recent investigation found corneal adaptation to suprathreshold stimuli in asymptomatic SCL wearers but not in symptomatic wearers, although there was no difference in thresholds between the 2 groups.44 All these findings show that the understanding of the relationship between CLD and sensitivity of the ocular surface is still limited. In summary, this study has demonstrated that the marginal conjunctiva is the most sensitive of all the conjunctival regions in SCL wearers and nonwearers alike. After a 12-hour period, SCL wearers showed decreased sensitivity of the lower marginal conjunctiva and increased lower lid margin staining compared with that of the nonwearers regardless of the symptom status. This work provides further insight into the interaction between the marginal conjunctiva and the contact lens surface and adds to the growing body of evidence linking the marginal conjunctiva and contact lens comfort.
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