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Factors Preventing Myopia Progression with Orthokeratology Correction

Santodomingo-Rubido, Jacinto*; Villa-Collar, César; Gilmartin, Bernard; Gutiérrez-Ortega, Ramón§

doi: 10.1097/OPX.0000000000000034
Original Articles

Purpose To examine which baseline measurements constitute predictive factors for axial length growth over 2 years in children wearing orthokeratology contact lenses (OK) and single-vision spectacles (SV).

Methods Sixty-one children were prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The primary outcome measure (dependent variable) was axial length change at 2 years relative to baseline. Other measurements (independent variables) were age, age of myopia onset, gender, myopia progression 2 years before baseline and baseline myopia, anterior chamber depth, corneal power and shape (p value), and iris and pupil diameters as well as parental refraction. The contribution of all independent variables to the 2-year change in axial length was assessed using univariate and multivariate regression analyses.

Results After univariate analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia (all p < 0.05). In multivariate analyses, older age and greater corneal power were associated with smaller increases in axial length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris diameter was associated with smaller increases in axial length (p = 0.021).

Conclusions Orthokeratology is a successful treatment option in controlling axial elongation compared to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia.

*OD, PhD, FAAO

MSc, PhD, FAAO

PhD, FCOptom, FAAO

§MD, PhD

Menicon Co., Ltd (Madrid Office) (JS-R); Clínica Oftalmológica Novovision (CV-C, RG-O); and Universidad Europea de Madrid (CV-C), Madrid, Spain; and School of Life and Health Sciences (BG), Aston University, Aston Triangle, Birmingham, United Kingdom.

Jacinto Santodomingo-Rubido Menicon Co., Ltd. (Madrid Office) Iglesia 9, Apartamento 106 Majadahonda, Madrid Spain e-mail: j.santodomingo@menicon.com

Myopia is now recognized as a common condition with prevalence levels in young adolescents approaching 10% to 25% and 60% to 80% in industrialized societies of West and East Asia, respectively.1,2 Furthermore, high myopia (i.e., ≤−6.00 D) is generally associated with a range of ocular pathologies, such as vitreous and retinal detachment, macular degeneration, and glaucoma.3–6 The rising prevalence of myopia has significant economic and social implications, resulting in interest in therapies to ameliorate its progression.7,8

Several treatment options have been used in the past, with limited success to eliminate, or at least reduce, myopia progression.9–11 Recent studies have reported orthokeratology contact lens wear to significantly reduce axial length growth by 30% to 50% in comparison to spectacle and soft contact lens wear.12–17 However, an important clinical issue that is unresolved is the identification of those children where orthokeratology is likely to be most effective.

The development of effective treatment strategies for control of myopia onset and progression requires a clear understanding of what governs the underlying physiological and biological processes. Previous studies have reported the association of baseline age and refraction on the axial growth of the eye in orthokeratology and spectacle lens wearers. Cho et al.12 reported smaller increases in axial length in children with higher and lower baseline myopia wearing orthokeratology contact lenses and spectacles, respectively. Similarly, Kakita et al.14 reported smaller increases in axial length in children with higher myopia at baseline wearing orthokeratology lenses, but they did not find baseline myopia to affect the rate of axial length growth in spectacles lens wearers. Hiraoka et al.15 extended the 2-year longitudinal study of Kakita et al. to follow up children for three additional years. The latter study also reported higher baseline myopia to be associated with smaller increases in axial length in orthokeratology lens wearers, but no association was found between baseline myopia and the rate of axial elongation in spectacle lens wearers.15 In addition, the latter study also reported smaller axial elongation with increasing age regardless of the treatment option assessed (i.e., orthokeratology or spectacles).15 More recently, Cho and Cheung17 also reported smaller axial elongation in children of older age wearing both orthokeratology contact lenses and spectacles, but no relationship was found between baseline myopia and the change in axial length in either of the study groups.

In addition to age and refractive error, other baseline demographics and refractive and biometric parameters as well as parents’ refractive status might contribute to axial elongation.18–22 For example, myopia has been reported to progress as a function of age between 6 and 14 years,18–20 with earlier onset of myopia resulting in greater progression of myopia and higher levels of end point myopia.20 Myopia has been shown to progress faster in females than in males.18–20 Anterior chamber depth, vitreous chamber depth, and axial length have been shown to increase with increasing myopia, although corneal power remains relatively stable.18,19 Children with parents who have myopia are at a higher risk of myopia development and progression, with the risk increasing with the number of parents with myopia.20–22

We have recently reported the results of a prospective study, the Myopia Control with Orthokeratology contact lenses in Spain (MCOS), which evaluated, as the primary outcome measure, differences in growth of axial length over a 2-year period in White European children with myopia wearing orthokeratology contact lenses (OK) and distance single-vision spectacles (SV).16,23 Thirty-one children were prospectively allocated to OK and 30 to SV. We found a statistically significant difference in axial length elongation relative to baseline between the OK (mean [standard deviation {SD}], 0.47 [0.18] mm) and SV (0.69 [0.32] mm) groups (p = 0.005). A number of additional measurements were recorded as part of the MCOS study: age of myopia onset, gender, and parental refractive error as well as children’s baseline age, refraction, anterior chamber depth, corneal power and shape, and iris and pupil diameters. The purpose of this study was to examine the degree to which these measurements affect the axial length growth over 2 years in children wearing OK and SV.

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METHODS

This study was part of the MCOS study designed to assess the safety, efficacy and subjective acceptance of OK versus SV in White European children with myopia over a 2-year period.16,23–25

Methods have been described in detail elsewhere.16,23–25 In brief, normal, healthy white European subjects 6 to 12 years of age with moderate levels of myopia (−0.75 to −4.00D) and astigmatism (≤1.00D) and free of systemic or ocular disease were recruited for the study and prospectively assigned to wear OK or SV. Spectacles or contact lenses, contact lens care solutions (for the OK group only), and full ocular examinations were provided free of charge to all subjects throughout the study. Full informed consent and child assent were obtained from the parents/guardians before the start of all experimental work and data collection. Patient participation in the study could be discontinued at the examiner’s discretion should significant symptoms or slit-lamp findings occur. Subjects were instructed they could withdraw from the study at anytime. The study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the Institutional Ethical Committee Review Board of Novovision Ophthalmology Clinic.

At the recruitment session, all subjects underwent a full anterior eye biomicroscopy, indirect fundus microscopy, binocular vision, and refractive evaluation to elucidate whether they were eligible to participate in the study; baseline study measurements were subsequently taken on eligible subjects (see below for full details of measurement procedures).

Subjects in the SV group were prescribed for constant wear distance single-vision spectacles having the highest positive/least negative power consistent with optimum visual acuity. Subjects from the OK group were fitted with Menicon Z Night contact lenses using Easy Fit Software (Menicon Co., Ltd., Nagoya, Japan). Contact lenses were ordered, and subjects from the OK group were rescheduled for an appointment approximately 2 weeks later. After initial contact lens fitting, all contact lens subjects were instructed on the first day on procedures for insertion, removal, and cleaning/disinfection and instructions were reinforced at subsequent visits. Subjects were provided with MeniCare Plus multipurpose solution for the daily cleaning, rinsing, and disinfecting of their contact lenses, and Menicon Progent intensive cleaner for use once a week (Menicon Co., Ltd).

After initial enrolment, subjects were followed at 1-, 6-, 12-, 18-, and 24-month intervals. Follow-up visits were scheduled to fall within 2 hours of awakening. A decrease in one line of visual acuity accompanied by a change in subjective refraction26 at any of the follow-up visits was considered clinically significant and was remedied by supplying contact lenses or spectacles made to the new prescription.

Cycloplegic autorefraction was performed after the instillation of three drops of cyclopentolate hydrochloride 1% (Alcon Cusí, Masnou, Barcelona, Spain) separated 10 minutes apart in each of the subjects’ eyes using a multidose bottle. Ten minutes after the instillation of the third drop, three autorefraction measurements were taken (Topcon RM 8000B, CA) and a mean was obtained.

Measurements of axial length and anterior chamber depth were taken with the Zeiss IOLMaster (Carl Zeiss GmbH, Jena, Germany).27 Three separate measurements of axial length were recorded, whereas a single shot automatically generated five measures of anterior chamber depth.

Corneal topography measurements were performed with the WaveLight Allegro Topolyzer (WaveLight Laser Technologies AG, Erlangen, Germany). The first measurement taken for each eye (which provided an optimum index value according to the manufacturer’s recommendations) was used for the study. Mean corneal power was calculated by averaging the powers of the mean flatter and steeper corneal meridians. Also, the measurement generated a simulated central keratometry reading and the rate of peripheral corneal flattening/steepening with displacement from the corneal apex, the latter indicating the degree to which an aspheric surface differs from the spherical form (i.e., p value).28 The p value was calculated over a 7-mm chord because this is the default setting of the instrument. In addition, iris and pupil diameters were also calculated automatically by the software.

Parental subjective refractions were taken at the baseline visit, and if required, parents provided estimates of the age of onset and progression of the child’s myopia over the 2 years before the beginning of the study.

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Statistical Analysis

Statistical analyses were conducted using SPSS 15.0 (SPSS, Inc., Chicago, IL). Data for the right eye only were used and expressed as mean (SD).

Differences in subjects’ demographics and baseline data between groups were tested using unpaired sample t-tests for all variables, except for the male/female ratio that was tested using a χ2 test.

The change in axial length at 2 years in comparison to baseline was taken as the dependent variable. Independent variables assessed as predictive factors for myopia progression were age, age of myopia onset, gender, myopia progression over the 2 years before the beginning of the study and baseline myopia, anterior chamber depth, mean corneal power and shape (i.e., p value), iris and pupil diameters, and parental refraction.

Simple linear regressions between the change in axial length and the different independent variables were calculated for each group separately and presented graphically (Figs. 1–11), with the exception of gender, which was assessed using a two-way analysis of variance. Differences between groups in the slopes of the regression lines were compared using analysis of covariance. Whenever analysis of covariance showed a significant interaction between independent and group variables, differences in the slopes of the regression lines between groups were tested using aptitude-by-treatment interaction to take into account individual differences in the process of treatment evaluation (Table 2).29 In addition, multivariate regression analysis was performed for each of the groups separately using the backward stepwise removal method. The F probability test was used to select each variable’s enter and exit criteria for the model. Factors that were significant at p < 0.2 were considered for multivariate testing. The strength of association for significant factors is summarized using beta values (±95% confidence intervals), corrected R2 values, and p values (Table 3).

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RESULTS

Sixty-nine children were initially examined for eligibility to participate in the study, but eight subjects could not be enrolled because they failed to meet the inclusion criteria for refraction. Thirty-one children were prospectively allocated to OK and 30 to SV. No statistically significant differences were found between groups in any of the variables assessed (Table 1; p > 0.05),16,23 with the exception of pupil diameter that was larger in the OK than the SV group (p = 0.005). Two and six children from the OK and SV groups, respectively, discontinued the study.24 In the OK group, one child discontinued the study owing to discomfort with contact lens wear and another child owing to unknown reasons. In the SV group, four children were lost to follow-up and another two children sought contact lens correction.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

TABLE 3

TABLE 3

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Univariate Analysis

Generally, the older the age at baseline, the smaller the axial elongation at 2 years in both study groups, although the relationship was not statistically significant in either the OK (R2 = 0.119, p = 0.060) or the SV group (R2 = 0.023, p = 0.227). However, the effect of baseline age on axial elongation was greater in the OK group in comparison to the SV group (Fig. 1 and Table 2, p = 0.001). Similarly, the later the myopia onset, the smaller the axial elongation; regressions were statistically significant for the OK group (R2 = 0.268, p = 0.002) but not for the SV group (R2 = 0.119, p = 0.096). Age of myopia onset was found to have a stronger effect in axial elongation in the SV group in comparison to the OK group (Fig. 2 and Table 2, p = 0.007).

Female gender was associated with smaller increases in axial length (0.52 [0.26] mm) in comparison to male gender (0.62 [0.29] mm) irrespective of the type of visual correction (p = 0.002). The interaction between gender and visual correction type was also statistically significant, indicating that female OK wearers were the subgroup that experienced smaller axial elongation at 2 years (p = 0.001).

Smaller myopic shifts 2 years before baseline were associated with smaller increases in axial length in the OK group, but the opposite was found in the SV group. Although these relationships were not statistically significant in either the OK (R2 = 0.095, p = 0.065) or the SV group (R2 = 0.017, p = 0.597), statistically significant differences were found between groups in the slopes of the regression lines (Fig. 3 and Table 2, p = 0.025).

The smaller the baseline myopia the smaller the increase in axial length in both study groups, although none of the two relationships was found to be statistically significant (both p > 0.05). However, a steeper regression line was found for the OK group in comparison to the SV group, indicating a greater effect in controlling axial elongation in subjects with lower baseline myopia in the OK group than in the SV group (Fig. 4 and Table 2, p = 0.007).

Longer anterior chamber depths were associated with smaller increases in axial length in the OK group (R2 = 0.184, p = 0.012), but the opposite was found in the SV group, although the latter relationship was not statistically significant (R2 = −0.039, p = 0.725). Statistically significant differences were found between groups in the slopes of the regression lines (Fig. 5 and Table 2, p = 0.003).

Greater corneal powers were associated with smaller increases in axial length in the OK group (R2 = 0.230, p = 0.005), but the opposite was found in the SV group, although the latter relationship was not statistically significant (R2 = 0.054, p = 0.142). Statistically significant differences were found between groups in the slopes of the regression lines (Fig. 6 and Table 2, p = 0.004).

The less prolate the corneal shape, the smaller the increase in axial length at 2 years in both study groups, although these such relationships were not statistically significant in either of the groups (both p > 0.05). However, the effect of corneal shape on axial elongation was greater in the SV group in comparison to the OK group (Fig. 7 and Table 2, p = 0.003).

The smaller the iris diameter, the smaller the increase in axial length at 2 years in both study groups, although these relationships were not statistically significant in either the OK (R2 = 0.044, p = 0.147) or the SV group (R2 = 0.038, p = 0.196). However, the effect of iris diameter on the change in axial length was greater in SV group in comparison to the OK group (Fig. 8 and Table 2, p = 0.002).

The larger the pupil diameter in the OK group and the smaller the pupil diameter in SV group the smaller the increase in axial length. Although the latter relationships were not statistically significant (p > 0.05), statistically significant differences were found between groups in the slopes of the regression lines (Fig. 9 and Table 2, p < 0.001).

Father’s refraction did not affect axial length change in either the OK (R2 = 0.046, p = 0.391) or the SV group (R2 = 0.002, p = 0.902). However, statistically significant differences were found between groups in the slopes of the regression lines (Fig. 10 and Table 2, p = 0.016).

Lower levels of myopia in the mother were associated with smaller increases in axial length in the OK group, whereas the opposite was found for the SV group, although none of two relationships was found to be statistically significant (R2 = 0.021 and p = 0.575; R2 = 0.099 and p = 0.347, respectively). However, statistically significant differences were found between groups in the slopes of the regression lines (Fig. 11, p = 0.026).

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Multivariate Analysis

In the OK group, children of older age, later onset of myopia, greater corneal power, and larger iris and pupil diameters at baseline exhibited smaller increases in axial length at 2 years (Table 3), although age and mean corneal power were the only statistically significant factors in the model (both p < 0.05). In the SV group, later onset of myopia, longer anterior chamber depth, lower corneal power, and smaller iris diameter exhibited smaller increases in axial length (Table 3), but iris diameter was the only statistically significant factor in the model (p < 0.05).

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DISCUSSION

We found subjects’ demographics, baseline refractive and biometric data, and parental refraction to have a differential effect on the axial elongation occurring with OK and SV correction, indicating that myopia progression is a complex and multifactorial clinical phenomenon. Nevertheless, this study has attempted to identify those children where orthokeratology is likely to be most effective in controlling myopia progression.

After univariate regression analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia. In multivariate analyses, older age and greater corneal power were associated to smaller increases in axial length in OK wearers, whereas smaller iris diameter was associated to smaller increases in axial length in SV wearers.

It is well established that older age and later onset of myopia are associated with smaller increases in myopia regardless of the visual correction tested in this study.15,17–19 The mechanism whereby older age has a greater effect in controlling axial elongation with OK in comparison to SV group is unclear.

We did not find baseline myopia to be significantly associated with axial elongation of the eye when either univariate or multivariate regression analyses were used in each of the groups separately (Fig. 4). However, the steeper regression line found for the OK group in comparison to the SV group (Fig. 4 and Table 2) indicates a greater effect in controlling axial elongation in subjects with lower baseline myopia in the OK group than in the SV group. The latter result is consistent with that of a recent study that used the same contact lens design as that used in the current study.17 In contrast, other studies have reported smaller axial elongation in OK wearers with higher baseline myopia.12,14,15 The discrepancy might be related to differences in the contact lens designs used and how these affected the peripheral refraction of the eye30,31 as this, in turn, could affect myopia progression.32

The OK group exhibited smaller increases in axial length, which were associated with longer anterior chamber depths, whereas no association between these two variables was found for the SV group (Fig. 5). However, the significant differences in the slope of the regression lines between groups (Fig. 5 and Table 2) indicate that longer anterior chamber depths might be conductive to myopia progression control in children fitted with OK in comparison to children prescribed SV. Small increases in anterior chamber depth are expected in children with myopia of around 10 years of age over a 2-year period.18,19 Therefore, children with shorter anterior chamber depths at baseline might be more likely to experience an increase in the depth of the anterior chamber concomitant with an axial elongation of the eye.

Greater corneal power was found to be associated with smaller axial elongation in OK wearers (Fig. 6). It is well established that corneal shape is one of the most determinant factors associated with successful OK lens wear.33 A steeper cornea allows greater redistribution of corneal epithelial tissue from the central to the peripheral cornea in OK lens wearers.34 The redistribution could conceivably reduce the amount of peripheral hyperopic defocus,30,31 which is considered to be a putative stimulus for axial elongation.35,36 The SV group did not show a significant association between corneal power and axial elongation, which agrees with previous studies whereby little change in corneal power was found in children with progressing myopia.18,19

We found that the larger the pupil diameter in the OK group, the smaller the increase in axial length, a finding in agreement with a recent study.37 It is possible that a larger pupil diameter coupled with redistribution of corneal epithelial tissue from the central to the peripheral cornea34 in the OK group produces a reduction in peripheral hyperopic defocus,30,31 leading to smaller increases in axial length.35,36

The differences in slope between groups with regard to parental refraction indicate that the lower the parental myopia, the smaller the increase in axial length in the OK group, whereas the opposite was found for the SV group (Figs. 10 and 11, and Table 2). Children with parents who have myopia have been reported to be at a higher risk of myopia onset and progression, with the risk21,22 and amount of progression38 increasing with the number of parents with myopia. However, the mechanism whereby, for OK versus SV wear, lower levels of parental myopia are associated with shorter increases in axial elongation is unclear.

A limitation of this study was that several variables were tested as contributory factors to the change in axial elongation despite the relatively small sample size used. Future studies with larger sample sizes should be undertaken to better understand factors affecting myopia progression in OK and SV wearers. Nevertheless, we have been able to identify a number of factors which affect significantly myopia progression, as measured by the axial elongation of the eye, in OK and SV wearers. Specifically, the data suggest that OK is a successful treatment option in controlling axial elongation in comparison to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia. Although there are factors not assessed in this study, which could contribute to myopia progression such as near work,39 time spent outdoors,40 dietary intake,41 and peripheral refraction,30,31 it is envisaged that the results of this study will assist eye care practitioners in identifying children at greater risk of myopia progression when corrected with OK and SV as well as those children who are likely to benefit most from OK for controlling myopia progression.

Jacinto Santodomingo-Rubido

Menicon Co., Ltd. (Madrid Office)

Iglesia 9, Apartamento 106

Majadahonda, Madrid

Spain

e-mail: j.santodomingo@menicon.com

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ACKNOWLEDGMENTS

The authors thank Dr. Hetal Patel, Prof. James Wolffsohn, and Prof. Fiona Stapleton for assistance in statistical analysis. The authors also thank the clinical and technical staff at Novovision in the acquisition of the data for this study and EURO-OPTICA for help in recruiting subjects for the study. Jacinto Santodomingo-Rubido is a full-time employee of Menicon. This work was partly funded by Menicon Co., Ltd.

Received: September 6, 2012; accepted May 1, 2013.

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Keywords:

myopigenic factors; myopia control; orthokeratology; axial length; myopia progression; eye elongation

© 2013 American Academy of Optometry