ORIGINAL ARTICLE. Corneal Refractive Therapy with Different Lens Materials, Part 1: Corneal, Stromal, and Epithelial Thickness Changes

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1 /07/ /0 VOL. 84, NO. 4, PP OPTOMETRY AND VISION SCIENCE Copyright 2007 American Academy of Optometry ORIGINAL ARTICLE Corneal Refractive Therapy with Different Lens Materials, Part 1: Corneal, Stromal, and Epithelial Thickness Changes SAMEENA HAQUE, PhD, BSc, MCOptom, DESMOND FONN, DipOptom Moptom, FAAO, TREFFORD SIMPSON, PhD, DipOptom, FAAO, and LYNDON JONES, PhD, FCOptom, FAAO Centre for Contact Lens Research, School of Optometry, University of Waterloo, Waterloo, Ontario, Canada ABSTRACT Purpose. To assess the corneal swelling response to two myopic correction corneal refractive therapy (CRT) lenses of varying Dk/t values, worn for a single night. Change in thickness of the total cornea, stroma, and epithelium was measured across the horizontal meridian using optical coherence tomography (OCT). Methods. In this double-masked, randomized study, twenty subjects wore a CRT design lens in each eye, manufactured from Menicon Z (MenZ; Dk/t 91) and Equalens II (EqII; Dk/t 47) materials. Baseline corneal thickness was measured centrally and at four points either side of the central cornea using OCT, the night before sleeping at the Centre for Contact Lens Research. The next morning, lenses were removed, and thickness measurements were repeated 1, 3, 6, and 12 h after removal. Results. On lens removal, the MenZ eye had central and paracentral corneal swelling (mean SD) of % and %, and the EqII eye had % and %. These values were significantly different from baseline (ReANOVA; p 0.001) and were different between lens materials (p 0.001). The central epithelium thinned by % in the MenZ eye and by % in the EqII eye, with the mid-peripheral epithelium thickening by % in the MenZ eye and % in the EqII eye (all changes different from baseline p 0.001). These epithelial values were not statistically different between materials (p 0.05). Stromal swelling values on lens removal were % centrally and % mid-peripherally (MenZ) and % centrally and % mid-peripherally (EqII) (all p from baseline). Central stromal swelling was different between eyes at lens removal (p 0.001). Stromal thickness in both eyes returned to baseline values within 3 h. Conclusion. The higher-dk/t MenZ material caused significantly less overnight corneal and stromal swelling than the Eqll material, which reinforces the need to prescribe lenses with high Dk/t for overnight wear. Neither central epithelial thinning nor paracentral thickening are significantly affected by Dk/t. (Optom Vis Sci 2007;84: ) Key Words: orthokeratology, corneal refractive therapy, optical coherence tomography, oxygen transmission, epithelium, corneal swelling Corneal refractive therapy (CRT) is a modern form of orthokeratology, in which rigid gas permeable (RGP) contact lenses are worn overnight to reduce refractive error. 1 3 In the treatment of myopia, attempts are made to flatten the central cornea. 2,4 The reduction in myopia is temporary, with regression occurring slowly throughout the day after removal of the CRT lens; however, regression is dependent on how long the lens is worn. 2,5,6 CRT lenses are currently approved for overnight wear, being typically worn during the night and removed every morning. Overnight wear of lenses clearly places an extra physiological burden upon the cornea, which makes oxygen transmissibility all the more critical to minimize corneal swelling. The degree to which oxygen may pass through a contact lens is governed by its oxygen transmissibility [Dk/t units 10 9 (cm ml O 2 )(s ml mm Hg)]. 7 One method of assessing the effect of oxygen transmissibility of a contact

2 344 Corneal Refractive Therapy: Thickness Changes Haque et al. lens is measuring the amount of corneal swelling that occurs after overnight lens wear, in addition to the normal physiological edema that results from eye closure after sleep. Normal physiological overnight corneal swelling is approximately 3 to 4% Two decades ago, Holden and Mertz 8 established the critical minimum oxygen transmissibility for overnight wear of contact lenses at (cm ml O 2 )(s ml mm Hg). However, more recent studies have suggested that they may have underestimated the value needed to avoid lens-induced corneal swelling. 7,10,15 CRT lenses (Paragon Vision Sciences) approved for use in North America are manufactured from the HDS100 material (fluorosilicone acrylate), and have a central Dk/t of only 67. Our previous studies investigating the clinical performance of the Paragon CRT design have shown that the central and paracentral cornea swells by 5 to 7% upon eyeopening, 5,6 supporting the notion that they provide insufficient oxygen. To date, few studies have reported the impact of increased oxygen transmissibility on corneal swelling during overnight orthokeratology lens wear The purpose of this study was to measure corneal, stromal, and epithelial thickness changes after a single night of CRT lens wear for the treatment of myopia. Two different lenses were used, consisting of the same design but manufactured from two different materials, one with a higher Dk/t than the other. Optical coherence tomography (OCT) was used to measure the corneal thickness changes, as previously described. 5,6,19 Instrumentation and Lenses A Humphrey-Zeiss OCT 2 system (Humphrey Systems, Dublin, CA) was used to measure corneal thickness across the horizontal meridian at nine points. A fixation device mounted on the OCT instrument aided in the capture of peripheral images, as described previously. 5 Subjects were asked to fixate each LED on the fixation device, while a video monitor aided in the alignment of the incident beam on the correct corneal location and the image was captured. Each cross-sectional scan of the cornea was 1.13 mm in length and enabled the compilation of a thickness profile of the cornea along the horizontal meridian. Each eye of all subjects was fitted with a CRT lens of the Paragon design (Paragon Vision Sciences, Mesa, AZ) and randomly chosen to wear either a lens manufactured from the Equalens II material (Bausch & Lomb, Rochester, NY) or the Menicon Z material (Menicon, Nagoya, Japan). The Equalens II (EqII) lens material (fluorosilicone acrylate) had a Dk of , and the Menicon Z (MenZ) lens material (fluorosiloxanylstyrene) had a Dk of (Fatt polarographic method without edge correction). Both lenses had a center thickness of 0.18 mm. The lenses were fitted using the manufacturer s guidelines to achieve appropriate apical touch (4 mm), mid-peripheral clearance, adequate edge lift, and proper centration. The lens parameters are listed in Table 2. MATERIALS AND METHODS Subjects Twenty subjects were enrolled (13 females and 7 males; mean age years; ranging from 19 to 35 years). Neophytes and soft lens wearers were recruited, but current RGP lens wearers were excluded. This research was conducted after the tenets of the Declaration of Helsinki. Informed consent was obtained from each individual and ethics clearance was obtained from the Office of Research Ethics at the University of Waterloo, before commencement of the study. Each subject presented without history of ocular disease or surgery. Refractive error of participants was restricted to a spherical range of 1.00 to 6.00, with no more than 1.75-D cylinder. Mean baseline corneal parameters for the cohort are displayed in Table 1. TABLE 1. Baseline ocular parameters for the cohort Baseline ocular parameters (mean SD) Menicon Z Equalens II Refractive error Sphere (D) Cylinder (D) Keratometry Flat K (D) Cyl (D) Central corneal thickness ( m) Central epithelial thickness ( m) Procedures In the evening before sleeping at our facility, baseline measurements for corneal thickness were obtained. The CRT lenses were placed on eye and the participants slept at 10 p.m., to be woken at 7 a.m. the next morning. On waking, the subjects were asked to keep their eyes closed until the lenses were removed one at a time at the OCT instrument and corneal measurements taken. These were repeated 1, 3, 6, and 12 h after lens removal. Data Analysis Raw data files captured by the OCT were processed using custom software as described previously. 5,6,19 Corneal and epithelial thickness changes were expressed as a percentage change, compared to baseline. 5 Statistical analysis of the thickness measurements was performed using Statistica 7.0 (Statsoft Inc, Tulsa, OK). Repeated measures analysis of TABLE 2. CRT lens parameters Menicon Z Equalens II BOZR (mm) (mean SD) Return zone depth ( m) (mean SD) Landing zone angle (degrees) (mean SD) Total diameter (mm) Center thickness (mm) Power (D) Dk/t (10 9 barrers/cm) BOZR, back optic zone radius; Dk/t, oxygen transmissibility.

3 Corneal Refractive Therapy: Thickness Changes Haque et al. 345 FIGURE 1. Change in total corneal thickness after CRT lens wear using two different lens materials. variance (Re-ANOVA), Tukey Honestly Significant Difference (HSD) post hoc testing, and paired t tests were used to analyze the changes in thickness from baseline levels over the study period. The level for statistical significance was set at RESULTS All 20 subjects completed the study. At lens removal, the central and paracentral corneal swelling (mean SD) of the MenZ lens wearing eye was % and %, respectively, (ReANOVA; both p from baseline). Corneal swelling in response to the EqII lens was % and %, respectively (both p from baseline) (Fig. 1). (Paracentral values were taken as the average of the two nasal and two temporal points closest to the center.) These values were significantly different between lens materials (p 0.01). Corneal swelling from both lenses had returned to baseline levels within 3hoflens removal (p 0.05), as shown in Fig. 1. Stromal swelling in the MenZ wearing eye was % centrally and % paracentrally, and in the EqII-wearing eye, the stroma swelled by % centrally and % paracentrally after lens removal (all p from baseline) (Fig. 2). In comparing both lens materials, the central and paracentral stromal swelling caused by the EqII lens was significantly greater than that caused by the MenZ lens (both p 0.05). Stromal swelling from both lenses had returned to baseline levels within 3 h after lens removal (p 0.05), as shown in Fig. 2. On lens removal, the central epithelium had thinned by % in the MenZ wearing eye and similarly by % in the EqII wearing eye (both p 0.001, compared to baseline) (Fig. 3). There was no difference in epithelial thinning between lenses (p 0.05). The paracentral epithelium thickened by % in the MenZ wearing eye and % in the EqII wearing eye (both p from baseline). Paracentral epithelial thickening was not statistically significant between lens materials (p 0.21). After 12 h, the central epithelium had not completely returned to baseline levels, being still % thinner in the MenZ eye (p 0.05 from baseline) and % thinner in the EqII eye (p 0.05 from baseline). The paracentral epithelium in the MenZ eye had recovered to baseline levels after 12 h ( %, p 0.05), but in the EqII eye, it remained significantly thicker than baseline ( %, p 0.05). DISCUSSION This single night study compared two identically designed CRT lenses for the reduction of myopia manufactured from two lens materials of differing oxygen transmissibility (Dk/t). The work of Holden and Mertz 8,9 and Harvitt and Bonanno 7 suggested that an oxygen transmissibility of between 87 and is necessary to prevent overnight hypoxia and subsequent corneal swelling induced by the lens. The degree of stromal and corneal swelling measured in this study supports their suggestions, in that both lenses exhibited greater swelling than has been reported for average overnight corneal swelling of 3 to 4% without lens wear These results show that oxygen transmissibility has a significant effect on corneal swelling after overnight wear of CRT contact lenses. The central and paracentral corneal and stromal swelling induced by the Equalens II lens was higher than that induced by the Menicon Z lens (Figs. 1 and 2). Recently, Lum and Swarbrick 18 also compared two orthokeratology lenses of differing Dk/t (46 vs. 26 units), and concluded that

4 346 Corneal Refractive Therapy: Thickness Changes Haque et al. FIGURE 2. Stromal swelling and recovery after CRT lens wear using two different lens materials. lens Dk/t influenced the clinical outcome after overnight wear. In their study, the lens of higher Dk/t produced less central stromal swelling (2.3% vs. 5.7%, measured with the Holden-Payor optical pachymeter). The amount of swelling measured after 2 weeks of lens wear was reduced, which may be due to an adaptation to the reduced oxygen available. Our group has previously reported a similar observation during 4 weeks of myopic CRT lens wear. 5 FIGURE 3. Change in epithelial thickness after CRT lens wear using two different lens materials.

5 Corneal Refractive Therapy: Thickness Changes Haque et al. 347 CRT or orthokeratology lenses, when designed to reduce myopia will flatten the central area of the cornea resulting in suppression of central corneal swelling during overnight wear. 20 This is as a result of the mechanical pressure from the eyelid and lens on the central part of the cornea during eye closure. However, the pressure effects do not seem to extend much beyond the epithelium. This can be seen by comparing the profile thicknesses of the epithelium, stroma, and cornea in the three figures. The stromal thickness profiles from both lenses show more typical swelling profiles compared with the corneal profiles that show less central than paracentral swelling. This is partly due to the influence of the epithelial changes, which thinned centrally and thickened paracentrally. The change in central epithelial thickness did not differ between lenses, with each producing 10% epithelial thinning after lens removal. This value is slightly higher than that reported in a previous study where subjects also only wore the lenses for one night. 5 However, other investigators have measured as much as 32% central epithelial thinning after one night of lens wear. 21 Many lenses currently available are manufactured from the Boston XO material (Bausch & Lomb, NY) with a Dk of 100 (e.g., Contex OK, DreamLens, BE Retainer) and thus a Dk/t of approximately 67. Tahhan et al. 22 and Soni et al. 23 have compared these different lens designs and found little difference in the effectiveness of the procedure for myopic correction. Identical lens designs are not expected to lead to differences in refractive effects. 22,23 Mid-peripheral epithelial changes were dissimilar between EqII lens wear (18%) and with MenZ lens wear (13%), although this difference did not reach statistical significance. The paracentral area of epithelial thickening corresponds to the return (clearance) zone of the lens between the central bearing area and the landing (peripheral alignment curve) zone, which is 1 mm wide. It is within this clearance zone that the epithelium thickens (Fig. 3). There are a number of possible reasons for the thickening. The most likely is the negative pressure in this tear layer space causing the epithelium to bulge as described by Mountford. 4 Another possibility is the central lens bearing forces, redistributing the epithelial cells from the center outward into the space of the clearance area. The third reason for the localized increase in epithelial thickness is due to hypoxia. However, this is the least likely reason as the majority of in vivo studies have shown that the epithelium does not thicken in response to hypoxia Recovery of corneal and stromal swelling occurred within 3 hours after lens removal, as has been reported in previous studies. 5,6 Results from this study showed that epithelial recovery was more gradual and incomplete, which is also in agreement with previous reports. 5,21,27,28 In conclusion, this study has shown effects of CRT lens wear on corneal and epithelial thickness after a single night of wear, comparing two different Dk lens materials. There were differences in corneal and stromal swelling induced by the two lenses, but no differences in central epithelial thinning or paracentral thickening. The results of this study reinforce the need to prescribe lenses with the highest oxygen transmissibility if they are to be worn overnight. ACKNOWLEDGEMENTS This work was supported by Menicon, Paragon Vision Sciences and an equipment grant from the Canada Foundation for Innovation (CFI). This work was presented as a lecture at the American Academy of Optometry (AAO) annual meeting in San Diego, CA, on Friday, December 8, 2005 (Program number: ). None of the authors of this study have any financial or other interests/ arrangements with the products/companies mentioned in the manuscript. Received July 7, 2006; revision received September 5, REFERENCES 1. Dave T, Ruston D. Current trends in modern orthokeratology. Ophthalmic Physiol Opt 1998;18: Swarbrick HA, Wong G, O Leary DJ. Corneal response to orthokeratology. Optom Vis Sci 1998;75: Mountford J. Orthokeratology. In: Phillips A, Speedwell L, eds. Contact Lenses. Oxford: Butterworth-Heinemann; 1997: Mountford J. An analysis of the changes in corneal shape and refractive error induced by accelerated orthokeratology. 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