Skip Navigation LinksHome > November 2012 - Volume 89 - Issue 11 > Impact of Pupil Diameter on Axial Growth in Orthokeratology
Optometry & Vision Science:
doi: 10.1097/OPX.0b013e31826c1831
Original Articles

Impact of Pupil Diameter on Axial Growth in Orthokeratology

Chen, Zhi*; Niu, Lingling; Xue, Feng*; Qu, Xiaomei*; Zhou, Zimei*; Zhou, Xingtao*; Chu, Renyuan*

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Author Information

*MD, PhD

MD, MSc

Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China (ZC, LN, FX, XQ, XZ, RC), and Department of Ophthalmology, Bronx Lebanon Hospital Center, Albert Einstein College of Medicine, New York, New York (ZZ).

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Abstract

Purpose. To compare axial elongation between myopic orthokeratology (OK) contact lens and spectacle wearers, and to investigate the impact of pupil diameter on axial growth in myopic children after OK treatment.

Methods. Fifty-two Chinese children aged 9 to 14 years were enrolled in this study, 27 for the OK group and 25 for the single vision spectacle lenses (SVL) group. Subjects in each group were further divided into two subcategories according to their baseline scotopic pupil diameters. Axial length (AL) was measured at baseline and at every 6-month visit through to 24 months. Linear mixed-effect model was used to determine myopia progression (AL changes from baseline). In this model, repeated visits were taken as within-subject effect, and treatment group as well as pupil size were taken as between-subject effects. The interaction of treatment group*pupil size was analyzed. Relationships between axial growth at 24 months and baseline pupil area were analyzed in both lens groups.

Results. Twenty-five subjects in the OK group and 22 subjects in the SVL group completed the 24-month study. AL increased significantly throughout the observed 24-month period (F = 32.09, p < 0.001). Pupil size significantly affected axial growth (F = 15.95, p < 0.001) and different treatment modalities (OK vs. SVL) interacted with the effect of pupil size on axial growth (F = 24.66, p < 0.001). To be more specific, axial growth was significantly slower in subjects with above average pupil sizes than those with below average pupil sizes in the OK group (F = 25.04, p < 0.001). Contrarily, pupil size did not affect axial growth in the SVL group (F = 0.46, p = 0.50). Baseline scotopic pupil area was significantly correlated to axial growth in the OK group (r2 = 0.405, p < 0.001) but not in the SVL group (r2 = 0.171, p = 0.056).

Conclusions. Large pupil diameters facilitate the effect of OK to slow axial growth in myopia. We speculate that this is because of enhancement of the myopic shift in the peripheral retina.

Previous studies have revealed that myopia development is both heredity based and environment influenced.1–6 Evidence has also shown that among all the factors affecting visual inputs, peripheral refraction plays an important role in refractive development in infant monkeys7,8 and children.9 Myopic eyes typically have a relatively hyperopic peripheral refractive error, whereas emmetropes and hyperopes have relatively myopic peripheral refractive errors.10,11 It has been proposed that inducing a relatively myopic peripheral defocus in myopic eyes might slow down or cease the progression of myopia.12 Hence, there has been great interest in methodologies that could possibly retard myopia progression through peripheral refraction manipulation.13

Orthokeratology (OK) is a procedure in which corneal curvature is altered by rigid gas-permeable contact lenses, with a reverse geometry design worn overnight. OK lenses are also known to induce myopic defocus in the peripheral retina.12 Several studies have documented slower myopia progression in children and adolescents who undergo OK therapy, compared with those wearing single vision spectacle lenses (SVL) or soft contact lenses.14–18 This phenomenon is believed to be attributable to the induced myopic shift in peripheral retina.12,19,20

Assimilating the ocular refractive system to an optical combination, pupil serves as a critical component as an aperture. Pupil dilation and constriction determine how much light actually enters the eye, and it predominantly blocks peripheral light beams when its size is small. In this regard, the pupil size (more specifically the pupil area) may actually influence the relative contribution of peripheral myopic defocus in OK therapy, and hence the eye growth in children wearing OK lenses. The current study was designed to compare the axial elongation between OK contact lens vs. spectacle wearers, and to examine the effects of pupil size on the control of myopic eye growth.

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METHODS

Subjects

The study was conducted between August 2008 and September 2010. Twenty-seven Chinese children aged 9 to 14 years, who visited Eye & ENT Hospital and met the inclusion criteria, were consecutively enrolled in the OK group. Twenty-five individuals who matched the inclusion criteria for OK group but preferred SVL served as controls. The inclusion criteria included good ocular health and free from any ocular disease; an apical corneal refractive power between 41.50 D and 44.50 D, refractive error between −1.00 D and −4.50 D, astigmatism <1.50 D, and monocular corrected distance visual acuity no worse than 20/20. Written informed consent was obtained from parents after the procedures, and possible risks were fully explained before initiation of treatment. This study conformed to the tenets of the Declaration of Helsinki.

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Lens Manipulation

In the OK group, subjects were fitted with OK lenses (Hiline Optics, China) in both eyes. The OK lenses were to be worn on an overnight basis, with no lens wear during the day. Four-zone reverse geometry lenses composed of fluorosilicone acrylate (Boston XO), with an oxygen permeability (Dk) of 100 × 10−11 (cm2/sec)(mL O2/mL · mm Hg) were used in the current study. The optic zone diameter was 6.0 mm. Lenses were fitted according to the instructions recommended by the manufacturer. In brief, for the first lens selection, alignment curve was decided based on the flatter keratometry readings, and base curve as the curvature of the flat meridian minus the target power minus 0.75 D. Slit lamp biomicroscopy with corneal fluorescent staining tests were performed 1 and 2 h after delivery of the lens. For a fit to be deemed acceptable, the contact lens had to be well centered on the cornea and to move approximately 1 mm on a blink. The overall fluorescent pattern resembled a classic bull’s eye, with a central touch surrounded by a narrow and deep annulus of tears trapped in the reverse curve area. Total diameters of the lenses were 10.6 mm in 23 cases and 10.8 mm in 4 cases. The subjects were reevaluated for compliance, lens position, visual acuity, and corneal topography 1 day, 1 week, and 1 month after delivery of the lenses. They were instructed to wear their lenses for at least 8 h per night and 6 days per week. Parents were requested to log their children’s OK lens wearing schedules and presented them to the unmasked researcher (Z.C.) at each follow-up visit.

In the SVL group, spectacle lenses were prescribed according to non-cycloplegic manifest refraction outcomes. The polycarbonate series single vision lenses (Essilor, France) were used. The subjects in the SVL group were instructed to wear their lenses at least 8 h on a daily basis.

A new prescription would be given if an SVL subject had a myopia progression equal to or greater than −0.50 D during follow-up visits. For the OK subjects, a new lens would be prescribed if monocular uncorrected distance visual acuity was equal to or worse than 20/25 during follow-up visits, or the scratch and abrasion of the lens had significantly affected continuation of lens wear.

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Measurements and Follow-Up Plans

All patients underwent ocular examinations that included slit lamp examination, manifest refraction, axial length (AL) measurement, and corneal topography at the time of enrollment and 6, 12, 18, and 24 months after the initial treatment. AL was measured by partial coherence interferometry (IOLMaster, Carl Zeiss, Germany) 5 times and automatically averaged. Corneal topography was taken by the Humphrey topographer (Carl Zeiss, Germany). To minimize the influence of diurnal variation, all measurements were conducted between 9 a.m. and 11 a.m. For subjects in the OK group, measurements were taken 2 to 4 h after lens removal.

Pupil size was measured before treatment and at the 24-month follow-up visit. The subjects were required to stay in a dark room for 30 minutes, and then scotopic pupil diameters were measured 3 times and averaged using the OPD-ScanII (NIDEK, Japan). Pupil area was calculated using the equation below:

Equation (Uncited)
Equation (Uncited)
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(A = pupil area, r = radius of the pupil). The average pupil diameter was calculated from all the subjects who completed the study and was used as the cutting point for dividing the cohort into “pupil size above average” vs. “pupil size below average” subcategories in the OK and SVL groups, respectively (four subgroups in total).

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Statistical Analysis

Unpaired t-tests were performed to compare age, baseline spherical equivalent refractive error, apical corneal power, and AL between the OK and SVL group. Linear mixed-effect model was used to determine myopia progression (AL changes from baseline). In this model, repeated visits were taken as within-subject effect, and treatment group as well as pupil size were taken as between-subject effects. The two-way interaction of treatment group*pupil size and three-way interaction of treatment group*pupil size*repeated visit were also analyzed. Baseline AL, gender, and age were tested in this model as covariates. Bonferroni corrections were applied for post hoc pairwise comparisons. In addition, Pearson correlation analysis was used to evaluate the relationship between baseline pupil area and AL change at the 24 month’s visit in the OK and SVL groups, respectively. Only right eyes of the subjects were analyzed in the current study.

To determine the total sample size, we sought 80% power to detect a 0.25 mm (about 0.75 D) difference in axial growth between the two groups, with a significance level of 0.05 (2-tailed). Assuming that the standard deviation of the change in AL during a 2-year period is 0.27 mm, the number of subjects required to complete the study in each group was 19. Taking into account a dropout rate of 20% at two years, at least 24 subjects in each group were needed for our study.

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RESULTS

Patient Demographics

Two subjects in the OK group dropped out of the study, one due to persistent poor distant visual acuity and the other moving out of country. Three subjects in the SVL group dropped out, all because of inability to keep follow-up appointments. Thus, 47 subjects completed the study, giving a dropout rate of 7.4% and 12.0% for the OK and SVL groups, respectively. For the subjects who completed the study, there were no significant differences in baseline spherical equivalent refractive error, apical corneal power, or AL between the OK and SVL groups (p > 0.05). The difference in age between the two groups was statistically significant (p = 0.001; Table 1).

Table 1
Table 1
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Pupil Size and AL

Baseline pupil diameters ranged from 5.12 to 7.90 mm for the OK subjects and from 4.92 to 8.08 mm for the SVL subjects. The average pupil diameter for all the subjects who completed the study was 6.43 ± 0.79 mm. The number of subjects in each subgroup divided by this critical value was shown in Table 2.

Table 2
Table 2
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Based on the linear mixed-effect model (Fig. 1), AL increased significantly throughout the observed 24-month period (F = 32.09, p < 0.001). Pupil size was found to significantly affect axial growth (F = 15.95, p < 0.001), and different treatment modalities (OK vs. SVL) interacted with the effect of pupil size on axial growth (F = 24.66, p < 0.001). To be more specific, in the OK group, axial growth was significantly slower in subjects with above average pupil sizes than those with below average pupil sizes (F = 25.04, p < 0.001). At the end of 24-month period, AL change (from baseline) in the OK subjects with above average pupil sizes was about half that of the OK subjects with below average pupil sizes. Contrarily, pupil size did not appear to affect axial growth in the SVL group (F = 0.46, p = 0.50). The respective effect of pupil size on axial growth within each lens group did not show a significant change over time (F = 0.96, p = 0.48). Age, gender, baseline AL, and treatment group were tested in the linear mixed-effect model, but none of them contributed significantly to the model (p > 0.05).

Figure 1
Figure 1
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Based on the Pearson correlation analysis, baseline pupil area was negatively correlated to axial growth at 24-month visit in the OK group (r2 = 0.405, p < 0.001; Fig. 2A). In contrast, no significant correlation was found between axial growth and baseline pupil area in the SVL group (r2 = 0.171, p = 0.056; Fig. 2B).

Figure 2
Figure 2
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DISCUSSION

There has been growing evidence that OK slows myopia progression in children and adolescents.14–18 Cho et al.14 reported that AL in children increased by 0.29 ± 0.27 mm in the OK group and by 0.54 ± 0.27 mm in the SVL group during a 2-year period. Walline et al.18 found that the mean increase in AL in the OK group was 0.25 mm compared with 0.57 mm in the control group after 2 years. Similarly, Kakita et al.16 revealed that the increase in AL was 0.39 ± 0.27 mm and 0.61 ± 0.24 mm in the OK and SVL groups during 2 years, respectively, the difference of which was statistically significant.

Despite the well-documented phenomenon that OK controls myopia, the underlying mechanism for such interference is not fully elucidated. One of the current hypotheses is that OK induces a myopic change in the peripheral refraction, which may protect against myopia progression.12,16,19,20 Experimental studies in primates support the concept that peripheral retina plays a decisive role in regulating ocular growth and refractive development. Peripheral form deprivation or lens-induced hyperopia was shown to cause qualitatively similar amount of axial myopia progression in infant monkeys, even without the participation of central retina.7,8 In human studies, Mutti et al.9 reported that children who became myopic had more hyperopic relative peripheral refractive errors than did emmetropes 2 years before the onset of myopia, indicating that peripheral hyperopic refractive error may be a potential predictor for myopia.

Should peripheral hyperopia be a cause of myopia progression rather than a consequence, introducing peripheral myopic defocus by means of optical intervention to those at higher risk would be of substantial value in clinical practice. Tse et al.21 as well as Tse and To22 used custom-made dual-power lenses to impose simultaneous myopic defocus and hyperopic defocus on young chick eyes. By modifying the relative proportion of hyperopic defocus, they found that the larger proportion of myopic defocus induced on the retina, the less likely that eyes will elongate.

OK lenses induce peripheral myopic shift more evidently in the far periphery than in the near periphery (i.e., ±30 degrees vs. ±10 degrees).12,19,20 Pupil size herein plays an important role, influencing the amount of penetrating light, with more peripheral rays penetrating through larger pupils than through smaller pupils. The current study provided strong evidence, showing a significantly negative correlation between the baseline pupil area and AL change at 24-month visit in the OK group. Children with larger pupils turned out to have significantly less myopia progression than those with smaller pupils in the OK group. Such phenomenon was not observed in the SVL group.

Other researchers have reported variations in the effect of myopia control by OK contact lenses.14,16 For example, Kakita et al.16 enrolled subjects with refractive error from −10.00 D to −0.50 D in their study and observed substantial variations in axial growth in the OK and SVL groups. They found a significant relationship between the increase in AL and baseline refractive error in the OK group and proposed that the variation in axial growth was due to different amount of peripheral hyperopia reduction among subjects.16 Consistently, Cho et al.14 reported a similar correlation between long-term axial growth and baseline refractive error in myopic OK treatment. Accordingly, we propose that the discrepancy in therapeutic effects among OK lens wearers in our study was attributable to the extent of “functional” reduction in peripheral hyperopia among subjects. A larger pupil diameter yielded a higher intensity of myopic defocus, thus exerting a greater suppressive effect on axial growth.

One of the limitations of the current study is that the patients were not randomly assigned into different treatment groups. In regard to this, we included covariates such as baseline AL, age, and gender to the linear mixed-effect model to adjust for observed differences between the two groups. Despite of these efforts, we believe that randomized clinical trial is still preferred in future study designs to control for other non-measurable variants between the two groups.

In the current study, only scotopic pupil size was assessed, which was more stable for the measurement. A photopic condition would otherwise mimic daily life conditions. Notwithstanding, the average differences in pupil diameters between scotopic and photopic conditions remain largely constant (1.5 mm) across the range of ages from 18 to 62 years.23 That would help us deduce the photopic pupil size from the scotopic one. In addition, our data showed that scotopic pupil diameters did not change after long-term OK therapy. This may bear predictive value as for who will benefit the most from OK treatment in terms of myopia control. Moreover, based on our data, a possible intervention (i.e., cycloplegic agent) may be of benefit to children with relatively small pupils who wish to undergo OK therapy.

In conclusion, our study provides evidence consistent with the notion that large pupil diameters facilitate the effect of OK to slow axial growth in myopia by enhancing the myopic shift in the peripheral retina.

Xingtao Zhou

Eye & ENT Hospital, Fudan University

No.19 Baoqing Rd, Shanghai, China

e-mail: xingtaozhou@163.com

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ACKNOWLEDGMENTS

The authors thank Helen Swarbrick and Chi-ho To for comments and advice on the manuscript. We also thank Yawen Chen and Yixiu Zhou for their statistical expertise. This work was supported by the National Natural Science Foundation of China, Grant 11074052. The authors have no financial interest in any of the products mentioned in the manuscript.

Received December 5, 2011; accepted July 8, 2012.

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Keywords:

orthokeratology; myopia; axial length; pupil diameter; peripheral refraction

© 2012 American Academy of Optometry

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