Normal corneal sensitivity is essential for the health of the ocular surface. Any reduction in sensitivity can compromise the lacrimal functional unit, leading to dry eye,1–4 as well as lessening the ability of the cornea to detect foreign bodies that could damage the ocular surface.5 Earlier studies have shown that contact lens wear reduces corneal sensitivity, potentially leading to an increased risk of infection.6–8 The amount of reduction in sensitivity is dependent on such factors as lens type and material (polymethyl methacrylate, rigid gas-permeable, hydrogel, or silicone hydrogel), wearing modality (daily or extended wear), and duration of wear.9–12 Subsequent studies suggested that the reduction in sensitivity is attributable to corneal hypoxia and consequent altered metabolic function.5,7,13 However, recent studies involving the wear of silicone hydrogel (SiHy) lenses showed that sensitivity is still reduced when corneal hypoxia is eliminated.14,15 This supports an earlier suggestion that additional factors, such as mechanical force, contribute to the sensitivity loss induced by contact lens wear.12 However, the relative contributions of these factors are currently unclear.
No study has specifically investigated the relationship between mechanical force (or pressure) applied to the cornea and sensitivity change during contact lens wear. During the wear of second-generation SiHy lenses, minimal pressure is applied to the cornea, as evidenced by their clinically nonsignificant effects on corneal topography.16 In conventional rigid gas-permeable (GP) lens wear, it is assumed that greater pressure is applied to the cornea than in SiHy lens wear because of the increased modulus of the lens material. Gas-permeable lenses fitted in alignment with the cornea will distribute this pressure evenly over the corneal surface. In orthokeratology (OK) lens wear, pressure is applied specifically to the central cornea through the tear film to reshape the corneal contour during closed-eye lens wear.17 Consequently, the pressure on the central cornea is considerably greater than in conventional GP lens wear. Therefore, comparing the induced changes in corneal sensitivity after overnight wear of these lens types may clarify the relative contributions of mechanical force to sensitivity loss during contact lens wear.
In humans, corneal sensitivity is measured by stimulating superficial nerve fibers and then recording the subsequent psychophysical response. Since its inception in the 1960s, the Cochet-Bonnet aesthesiometer (COBO) has been considered the gold standard for measuring corneal sensitivity. Consequently, most studies involving corneal sensitivity and contact lens wear have used this particular instrument. However, limitations in this particular instrument, such as the invasive nature of the stimulus, patient apprehension on seeing the thread approach his or her eye, and poor stimulus reproducibility,18 have resulted in the development of gas-jet aesthesiometer, such as the Non-Contact Corneal Aesthesiometer (NCCA). Such devices are noninvasive and therefore less confronting to subjects. They also possess a wider range of stimulus intensities; truncation is a major shortcoming of the COBO and leads to the clustering of measurements around the minimum stimulus intensity. Consequently, gas-jet aesthesiometers may potentially be a suitable replacement for the COBO as a new standard for ocular sensitivity measurements.
The primary aim of this study was to examine the changes in corneal sensitivity after a single overnight wear of contact lenses with different mechanical properties. Specifically, central corneal sensitivity was measured after overnight wear of three lens types: SiHy, GP, and OK. All lenses were matched for oxygen transmissibility (Dk/t) but assumed to exert different levels of mechanical pressure onto the corneal surface. We hypothesized that lenses exerting greater levels of mechanical pressure would cause greater sensitivity loss after overnight lens wear. In addition, as a secondary aim of the study, we measured corneal sensitivity using the COBO and NCCA to determine if threshold values were comparable between these two instruments.
Subjects presented for a baseline visit where corneal topography and sensitivity measurements were made on the right eye only and then dispensed a lens type for single overnight wear (∼8 hours) in the same eye. Subjects then returned the following day for data collection by an investigator masked to the lens type. All measurements, including baseline measurements, were made approximately 3 hours after waking and lens removal for logistical reasons, as well as to mitigate the influence of overnight corneal environmental changes, such as hypoxia, acidosis, increased temperature, and tear film changes. The next overnight wear was scheduled after a minimum washout period of 3 days. Because the COBO is known to cause slight disruption of the corneal surface,19 measurements using this instrument were taken after all other techniques at each visit.
A target sample size of 16 subjects was calculated based on power analysis using representative data from previously published studies in this area. An additional six subjects were included to allow for discontinuations during the study. After approval for the study had been obtained from the University of New South Wales Human Research Ethics Advisory Panel, subjects were recruited via advertisements placed on notice boards in the School of Optometry and Vision Science, University of New South Wales. Screening ensured that the following criteria were met: (1) aged between 18 and 45 years, (2) good ocular and physical health, (3) no history of ocular surgery or rigid lens wear, and (4) not pregnant. Existing soft contact lens wearers were asked to cease lens wear for a minimum of 3 days before the baseline visit. All subjects gave written consent to study participation after being informed fully of the risks and benefits of the measurement techniques and overnight contact lens wear.
Although there is currently no method of measuring the mechanical force exerted by contact lenses fitted on the cornea, it was assumed that the three lens types used in this study would exert different levels of mechanical force, resulting in varying degrees of corneal profile change. Hence, change in corneal profile was measured using the Medmont E300 corneal topographer (Medmont Pty Ltd, Melbourne, Australia) as a surrogate for direct measurement of mechanical force exerted by the lenses. Variables of interest included central corneal refractive power (in diopters [D]), apical radius of curvature ro (in millimeters), and asphericity Q over a 9.35-mm chord along the horizontal meridian.
Central corneal sensitivity measurements were carried out on the right eye only using two instruments: COBO aesthesiometer and NCCA.
COBO: The COBO used a nylon filament with a nominal diameter of 0.08 mm, but this was checked using a profile projector with manual X-Y measurement stage (Nikon toolmakers; precision, ±2 μm) before use. The instrument was mounted on a modified slit lamp biomicroscope so that its position and movement could be controlled in the X, Y, and Z meridians. Threshold values were determined using the guidelines as provided by Cochet and Bonnet.20 Lengths were converted into pressure (in grams per square millimeter) using a specifically calibrated curve for this instrument.
NCCA: The NCCA was based on the design described by Murphy et al.18 The stimulus consisted of a jet of medical quality air at room temperature (∼20°C) that passed through a 1.25-mm-diameter central bore for a duration of 0.9 seconds.
The stimulus area or footprint was estimated by mapping the force profile exerted by the air jet onto a flat surface. This force profile was mapped by mounting the air jet nozzle onto an X-Y axis stage, which was then placed so that the nozzle was 10 mm vertically above a small metal pin. The metal pin was mounted upright onto a microbalance scale (Sartorius Digital Balance R200D; precision, ±0.01 mg); the balance plate was shielded such that only the force from the jet of air registered on the scale via the metal pin. The force from the air jet was then measured, beginning with the nozzle directly above the pin (maximum force), then moved along the X-axis at 0.1-mm increments until no force registered on the scale. The X-axis distance from maximum to zero force gave an estimate of the footprint radius.
The air outflow was regulated using a manually controlled valve. The NCCA probe was positioned 10 mm away from the corneal apex by means of a small digital camera placed perpendicular to the subject’s visual axis. A computer screen displayed a real-time video image from the camera, ensuring accurate positioning of the probe relative to the corneal surface. Centration of the probe relative to the corneal apex was carried out visually. Threshold values were determined using the Garcia-Perez staircase method as described previously.21 Subjects indicated a positive response to the stimulus by activating a buzzer, as was the case with the COBO instrument.
Clinical slit lamp biomicroscopy was used to monitor corneal health and integrity after overnight lens wear at each measurement session. Corneal integrity was assessed with topical application of sodium fluorescein dye.
Subjects wore a SiHy (Acuvue Advance; Johnson & Johnson Vision Care, FL), GP (J-Contour; Capricornia Contact Lens, Brisbane, Australia), or OK (BE, Capricornia Contact Lens) lens in randomized order on separate occasions. Lenses were fitted according to standard techniques (SiHy), alignment with the cornea (GP), or according to manufacturer’s guidelines to target approximately 2.00 D reduction in myopia (OK). Lens center thicknesses were ordered to achieve a similar lens Dk/t of approximately 46 ISO units across all three lens types. Other characteristics of these lens types are presented in Table 1.
When comparing postwear to baseline measurements, normally distributed data were analyzed using repeated-measures analysis of variance (RM-ANOVA) with planned contrasts, and nonnormally distributed data were analyzed using the Friedman two-way analysis of variance by ranks, with post hoc Wilcoxon signed rank test. When comparing baseline measurements between lens wearers and non–lens wearers, nonnormally distributed data were analyzed using the Mann-Whitney U test (IBM SPSS statistics version 21; IBM, NY). A reported value of p < 0.05 denotes statistical significance. Correlations between corneal topography and sensitivity and between the two instruments were determined using Spearman rank order correlation.
A total of 22 subjects were initially enrolled into this study. Two male subjects were discontinued from this study: one because of excessive false-positive results during COBO sensitivity measurements and the other because of an inability to insert the SiHy lens. The 20 subjects who completed the study were 6 males and 14 females (mean age, 24 years; range, 19 to 39 years). Six of these subjects had previous experience wearing high-Dk SiHy lenses on a daily wear schedule, three of these on an occasional basis (<3 days per week).
There were significant differences between the three lens types in corneal topographic change from baseline after overnight lens wear for corneal refractive power (p < 0.001), apical radius (p < 0.001), and asphericity (p = 0.001). As expected, the change in refractive power from baseline (Fig. 1A) was greatest with lens type OK (0.72 ± 0.77 D), followed by GP (0.25 ± 0.61 D) and SiHy (0.13 ± 0.54 D). The change in refractive power was significant for the OK lens type only (p < 0.001). The change in apical radius from baseline (Fig. 1B) was again greatest with the OK lens type (0.13 ± 0.12 mm), followed by GP (0.02 ± 0.06 mm) and SiHy (−0.02 ± 0.07 mm). The change or flattening of the apical radius was significant for the OK lens type only (p < 0.001). Changes in asphericity (Fig. 1C) followed a similar pattern, with the greatest change from lens type OK (0.14 ± 0.15 mm), followed by GP (0.03 ± 0.05 mm) and SiHy (0.00 ± 0.06 mm). The change in asphericity from baseline was significant for the GP (p = 0.03) and OK (p = 0.001) lens types.
Central Corneal Sensitivity and Correlations
Using the COBO, there was no significant difference in baseline sensitivity measurements between preexisting lens wearers and non–lens wearers (p > 0.05). Significant differences were found between the three lens types in corneal sensation threshold change from baseline after overnight lens wear (SiHy, 0.02 ± 0.17 g/mm2; GP, 0.03 ± 0.20 g/mm2; OK, 0.22 ± 0.33 g/mm2; p = 0.002; Fig. 2). However, the increase in threshold from baseline was only significant for the OK lens type (p = 0.006). There was no correlation between the change from baseline in corneal sensation threshold and corneal refractive power (rs = 0.32, p > 0.05; Fig. 3), apical radius (rs = −0.05, p > 0.05), or asphericity (rs = 0.27, p > 0.05) following OK lens wear. There was no significant difference between the three lens types in corneal sensation threshold change from baseline using the NCCA (p > 0.05; Fig. 4).
Comparisons of corneal sensation threshold measurements obtained using the COBO and NCCA on each subject at each visit showed no correlation between these two instruments at baseline (rs = −0.16, p = 0.50) or after overnight wear of SiHy (rs = 0.14, p = 0.55), GP (rs = 0.01, p = 0.98), or OK (rs = 0.19, p = 0.42) lenses.
Aesthesiometer Stimulus Area
The diameter of the COBO nylon filament measured 0.099 mm, stimulating an area of approximately 0.008 mm2 on the corneal surface. The radius of the NCCA air jet footprint at 10 mm from the nozzle measured approximately 2 mm, stimulating an area of approximately 13 mm2 on the corneal surface.
This study showed that the single overnight wear of contact lenses altered corneal sensitivity, as measured using the COBO (Fig. 2). Specifically, it showed a decrease in the central corneal mechanical sensitivity after a single overnight wear of the OK lens type only. Sensitivity was unaffected by the single overnight wear of conventional GP or SiHy lenses.
The exact mechanism underlying the sensitivity loss after OK lens wear is unknown. Alterations in normal corneal metabolic function from reduced oxygen supply (or hypoxia) and increased carbon dioxide levels (leading to acidosis) have been suggested in earlier work as a primary cause of sensitivity loss during contact lens wear.5,7,13 However, in this study, this would be unlikely because all measurements were conducted when these corneal environmental changes after overnight lens wear,22 and the sensitivity loss following sleep,23 would had recovered. Sensory adaptation to thermal24,25 and mechanical26,27 stimuli in the human skin has been demonstrated in previous studies. We suggest that the sensitivity reduction found in this study could be caused by a sensory adaptation to the mechanical stimulus applied by the OK lenses to the corneal surface. The corneal topographic changes induced by these lenses were significantly greater than by the GP or SiHy lenses, confirming the greater mechanical impact of the OK lenses (Fig. 1). Sensory adaptation in the cornea as an etiological mechanism for sensitivity change5,28,29 was first suggested by Polse12 and recently demonstrated by Chen et al.30 using repeated corneal stimulation with suprathreshold jets of air. Alternatively, the observed sensitivity loss could be the result of changes to the architecture of corneal sensory nerve terminals, as we have demonstrated to occur in long-term OK lens wear.31 However, this seems unlikely because OK lens wear was only for a single night in this study, although this warrants further investigation.
A reduction in corneal sensitivity after medium-term OK lens wear has previously been shown by Hiraoka et al.32 In that study, the authors suggested further work to compare the effects of overnight wear of conventional GP with OK lenses to elucidate the contribution of the OK reverse-geometry design to the loss of sensitivity. In the present study, GP lenses, which differed from the OK lenses only in the lens design, induced no significant change in corneal sensation. This implies that the reverse-geometry design, and presumably the higher mechanical force applied to the cornea, is the primary cause of the sensitivity loss during short-term OK lens wear. Whether mechanical force is the primary factor accounting for the sensitivity loss in medium- to long-term OK lens wear requires further investigation.
Reductions in corneal sensitivity, as demonstrated in this study after OK lens wear, may potentially cause the contact lens wearer to become less aware of corneal trauma or the early critical stages of serious infections such as microbial keratitis. Although cases of microbial keratitis among OK wearers have been reported in seemingly disproportionately higher numbers compared with conventional rigid lens wearers, many of these microbial keratitis cases have been attributed to poor lens wear and care compliance in third-world countries.33 Nevertheless, reduced corneal sensitivity could also be a contributing factor. However, Hiraoka et al.32 reported a central corneal sensation threshold of 3.04 ± 2.85 g/mm2 after 3 months of OK treatment, which was similar to that reported for other contact lens modalities in previous studies using the COBO (i.e., 4.8 g/mm2 for daily PMMA lens wear, 1 to 2 g/mm2 during daily GP lens wear,34 approximately 3 g/mm2 during daily SiHy lens wear,15 and 3.5 g/mm2 in extended soft [hydrogel] lens wear35). In our study, we found a very much lower central corneal sensation threshold of 0.5 ± 0.5 g/mm2 after a single night of lens wear, which represents a very small reduction relative to those previously reported from longer periods of contact lens wear. Taken together, this evidence suggests that the relative risk of undetected trauma to the cornea from OK lens wear is likely to be no greater than for other types of contact lens. Whether the continued treatment of myopia using OK lenses for longer periods results in sensitivity reductions greater than those reported at 3 months by Hiraoka et al.32 requires further investigation. In the meantime, improvements in rigid lens materials and OK lens designs may reduce the impact of OK lens wear on corneal sensitivity.
In this study, we hypothesized that lenses exerting greater levels of mechanical pressure would cause greater sensitivity loss for lenses matched in Dk/t. This relationship was only partially supported because a significant change was only seen for the lens type that exerted greatest pressure (i.e., OK lenses). However, because the human cornea has been shown to recover from decreases in corneal sensitivity during contact lens wear36 and after extended eyelid closure,23,37,38 it is possible that a more pronounced lens pressure-induced corneal sensitivity reduction had occurred, but this had diminished by the time we conducted our measurements. Hence, we speculate that sensitivity outcomes from all lens types may have been more consistent with our hypothesis if sensitivity thresholds were measured sooner after eye opening than occurred in this study.
Although investigations of the relationship between the degree of change in corneal sensitivity and the change in corneal refractive power after OK lens wear was not a specific aim of this study, retrospective analysis of these results showed no correlation between these two parameters (Fig. 3). This is perhaps not surprising given that corneal topographic change may not be a perfect surrogate for the mechanical effects of contact lenses on the cornea but rather provides evidence for a difference in the mechanical effects between the three different lens types. In addition, this study involved only a single night of lens wear. This lack of correlation may also have been caused by the typical large individual variability in refractive change after the first overnight wear of OK lenses (as can be appreciated from inspection of Fig. 3), despite targeting a reduction in myopia of approximately 2.00 D in all subjects. A previous study39 has shown a significant variation in individual responses after short wearing periods that become more consistent during longer wearing periods. We may potentially have found a correlation between corneal topographic and sensitivity change had this study run for a 1- to 2-week lens wear period, which would have allowed more predictable and less variable topographic changes to emerge. Furthermore, we observed a clustering of sensitivity measurements toward the lower threshold levels with the COBO instrument (Fig. 3). These three factors, combined with the poor repeatability and reproducibility of the COBO technique,18,40 may explain the lack of correlation between sensitivity and topographic changes.
In this study, no change in threshold from baseline was detected using the NCCA for any of the lens types (Fig. 4). This differs from our findings using the COBO despite having the same subjects, lens types, and visits. A possible explanation for this difference includes the difference in stimulus footprint size on the corneal surface. The NCCA footprint is significantly larger than the COBO and, therefore, stimulates a greater number of corneal sensory receptors, thereby potentially obscuring any localized changes in sensitivity. Our finding of sensitivity changes with the COBO but not with the NCCA suggests that OK-induced changes in corneal sensitivity may be confined to the central cornea, and midperipheral or peripheral sensitivity may not be affected. Further investigation into the regional variation of corneal sensitivity during OK is necessary. In addition, positive responses to the NCCA stimulus are more likely to be caused by the stimulation of the polymodal and cold fibers resulting from the changes in corneal surface temperature, whereas responses to the COBO stimulus are more likely directly attributable to stimulation of the touch sensitive mechanosensory fibers.28,41,42 This suggests that the two instruments may measure different aspects of corneal sensitivity. If this is true, it is not surprising that corneal thresholds measured by each instrument showed no correlation, as has previously been reported.41 It therefore appears that outcomes from the two instruments are not necessarily comparable and, consequently, the NCCA should not be considered as a replacement for the COBO, particularly when investigating localized changes in corneal sensitivity.
In summary, we have demonstrated that a single overnight wear of OK lenses reduces central corneal sensitivity, as measured using the COBO. This suggests that mechanical force may play a role in the changes in corneal sensitivity during contact lens wear. Our results also suggest that the NCCA and COBO instruments may measure different aspects of corneal sensitivity and, therefore, measurements may not be comparable.
School of Optometry and Vision Science
The University of New South Wales
Sydney, New South Wales 2052,
This research was supported through the Australian Research Council Linkage Project Scheme, with industry partners Bausch + Lomb Boston (Wilmington, MA), BE Enterprises Pty Ltd (Brisbane, Australia), and Capricornia Contact Lens Pty Ltd (Brisbane, Australia). Lenses were supplied by Capricornia Contact Lens Pty Ltd and Johnson & Johnson Vision Care. Contact lens solutions were provided by Bausch + Lomb (Australia).
Received October 17, 2012; accepted April 25, 2013.
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