Myopia Control during Orthokeratology Lens

Wear in Children Using a Novel Study Design

Helen A. Swarbrick, PhD,1 Ahmed Alharbi, PhD,2 Kathleen Watt, BOptom,1 Edward Lum, PhD,1
Pauline Kang, PhD1

Purpose: To investigate the effect of overnight orthokeratology (OK) contact lens wear on axial length growth
in East Asian children with progressive myopia.
Design: A prospective, randomized, contralateral-eye crossover study conducted over a 1-year period.
Participants: We enrolled 26 myopic children (age range, 10.8e17.0 years) of East Asian ethnicity.
Methods: Subjects were fitted with overnight OK in 1 eye, chosen at random, and conventional rigid gas-
permeable (GP) lenses for daytime wear in the contralateral eye. Lenses were worn for 6 months. After a 2-week
recovery period without lens wear, lenseeye combinations were reversed and lens wear was continued for a
further 6 months, followed by another 2-week recovery period without lens wear. Axial eye length was monitored
at baseline and every 3 months using an IOLMaster biometer. Corneal topography (Medmont E300) and objective
refraction (Shin-Nippon NVision-K 5001 autorefractor) were also measured to confirm that OK lens wear was
efficacious in correcting myopia.
Main Outcome Measurements: Axial length elongation and myopia progression with OK were compared
with conventional daytime rigid contact lens wear.
Results: After 6 months of lens wear, axial length had increased by 0.04
0.06 mm (mean
standard de-
viation) in the GP eye (P ¼ 0.011) but showed no change (0.02
0.05 mm) in the OK eye (P ¼ 0.888). During the
second 6-month phase of lens wear, in the OK eye there was no change from baseline in axial length at 12
months (0.04
0.08 mm; P ¼ 0.218). However, in the GP eye, the 12-month increase in axial length was sig-
nificant (0.09
0.09 mm; P < 0.001). The GP lens-wearing eye showed progressive axial length growth throughout
the study.
Conclusions: These results provide evidence that, at least in the initial months of lens wear, overnight OK
inhibits axial eye growth and myopia progression compared with conventional GP lenses. Apparent shortening of
axial length early in OK lens wear may reflect the contribution of OK-induced central corneal thinning, combined
with choroidal thickening or recovery due to a reduction or neutralization of the myopiogenic stimulus to
eye growth in these myopic children. Ophthalmology 2014;-:1e11 ª 2014 by the American Academy of
Ophthalmology.

Myopia is among the most common refractive errors that 14.4%, and from 13% to 29.6% in 17-year-olds, over the
affect children. It is usually caused by excessive axial length study period.
of the eye, which causes light rays from distant objects to focus However, the highest myopia prevalence rates have
in front of the retina, giving rise to blurred distance vision. In consistently been reported from East Asian countries.
children, myopia is typically progressive in early to middle Epidemic levels of myopia prevalence have recently been
childhood.1 Early onset of myopia is frequently associated with reported from South Korea and China; 96.5% of 19-year-old
the development of high myopia,1 which can be associated South Korean males5 and 95.5% of Chinese university
with serious ocular complications, such as glaucoma, mac- students were found to have myopia.6
ular degeneration, and various pathologic retinal changes.1,2 There has been growing clinical and research interest
Thus, there are important benefits of interventions that might in developing strategies to control myopia progression,
slow or arrest the development of myopia in children. including both optical and pharmaceutical approaches.7 To
Myopia prevalence rates have been increasing worldwide. date, the most effective means for slowing myopia pro-
For example, in the United States the prevalence of myopia in gression is the use of atropine drops.7,8 Recent research
the 12- to 54-year-old population increased from 25% in 1971 using low concentrations of atropine (as low as 0.01%) seem
and 1972 to 41.6% in 1999 through 2004.3 In Australia, to avoid many of the problems of 1% atropine, such as loss
increasing myopia prevalence has also been reported; the of accommodation and pupil dilation, without significant
Sydney Adolescent Vascular and Eye Study (SAVES) fol- sacrifice of efficacy.9
lowed a group of children over 5 to 6 years.4 They reported an Optical approaches have included the use of bifocal and
increase in myopia prevalence in 12-year-olds from 1.4% to progressive addition lenses. Although these approaches do

 2014 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2014.09.028 1

Published by Elsevier Inc. ISSN 0161-6420/14
 Ophthalmology Volume -, Number -, Month 2014

have a small, statistically significant effect, their clinical in the research had been fully explained. Separate consent forms
effect is minimal, even when subgroups that show enhanced using appropriate language were prepared for subjects <10 years
efficacy are considered.10 More recently, spectacle lenses of age, >10 years of age, and for parents or guardians.
and contact lenses designed to manipulate the peripheral
retinal image have been investigated.11e13 These approaches Subjects
are based on the hypothesis developed by Smith et al14 that A total of 32 subjects who met the study entry criteria were
manipulation of the peripheral retinal image to maintain recruited for participation in this research. Inclusion criteria spec-
myopic rather than hyperopic defocus may act to inhibit ified age between 8 and 16 years at initial study enrollment and
axial eye growth. Results from clinical studies using such East Asian ethnicity (Chinese, Singaporean, Taiwanese, Malay-
optical manipulations have been encouraging. sian-Chinese, and Vietnamese) based on parental reports of ethnic
Orthokeratology (OK) is a well-established clinical background. Refractive criteria included myopia between 1.00
technique that involves wearing specialized rigid contact and 4.00 diopters (D) spherical equivalent, evidence of pro-
lenses with a reverse geometry lens design overnight. For gression of myopia in the previous 12 months (based on a reported
myopia correction, OK lenses flatten the central cornea to increase in spectacle prescription), <1.50 D of corneal toricity, and
<1.00 D difference in spherical equivalent refraction between the 2
correct mild to moderate degrees of central or on-axis myopia
eyes. For study entry, subjects also were required to demonstrate
after lens removal in the morning.15 Over the last few years, a good binocular coordination (based on a range of standard opto-
number of clinical studies have clearly demonstrated that metric tests of binocularity, including measurement of stereoacuity
overnight OK lens use in myopic children is effective in using the Titmus Fly Stereotest), good ocular health, and no con-
reducing the rate of myopia progression.16e23 It is hypothe- traindications for rigid contact lens wear.
sized that this effect results from the induction of myopic
defocus on to the peripheral retina as a result of the effects of Contact Lenses
the OK lenses on mid peripheral and peripheral corneal
topography.24 The rigid lenses used for overnight OK were of a reverse geometry
Previous studies of myopia control in OK have relied design (BE or A-BE; Capricornia Contact Lens Pty Ltd, Brisbane,
Qld, Australia) that is available commercially for use as an over-
on conventional study designs that have typically involved
night OK lens. Overall diameter of these lenses was either 11.00
separate study and control groups of children wearing lenses mm (BE) or 10.60 mm (A-BE), depending on the subject’s hori-
over 2-year study periods. Such clinical studies are cumber- zontal visible iris diameter and palpebral aperture dimensions. Both
some and expensive to conduct, require large sample sizes BE and A-BE lenses have an optic zone diameter of 6.00 mm, and
and carefully matched subject groups, and suffer from dif- specifications of the optic zone, first reverse curve, and peripheral
ficulties with maintaining subject matching over the lengthy alignment curve are identical between designs. The difference in
study period. Significant dropouts have been noted in lens diameter is achieved by using a slightly steeper and narrower
some of these studies, ranging from 13% to 46% overall and second reverse curve in the A-BE lens to maintain sagittal height
up to 54% in the OK treatment group,16e23 confounding the equivalence between the 2 designs.
conclusions that can safely be drawn, particularly when The conventional rigid gas-permeable (GP) lenses used were
a standard alignment fitting design (J-Contour, Capricornia), a
reasons for dropout differ between control and treatment
4-curve lens with an overall diameter of 10.00 or 10.50 mm, and a
groups.25 spherical back optic zone with a diameter of 8.50 or 9.00 mm,
In the study reported herein, we used a novel contralat- respectively. To achieve an acceptable lens fit, the Modcon lens
eral eye crossover study design to avoid many of the design (Capricornia) with an overall diameter of 10.00 mm, a
problems associated with previous conventional clinical spherical back optic zone of 7.90 mm in diameter, and a tangent
trials. Using this efficient strategy, a relatively short-term periphery, was used for 5 subjects during study phase 1 (2 of whom
study with minimal subject numbers was used to test the discontinued) and 4 subjects during study phase 2 (1 of whom
hypothesis that overnight OK lens wear inhibits axial elon- was refitted from a J-Contour to a Modcon lens). The choice of
gation and myopia progression compared with conventional lens design to use for the GP lens-wearing eye was based on
daytime rigid contact lens wear. The contralateral eye study conventional rigid contact lens fitting considerations to encourage
comfortable and safe daily GP lens wear.
design allowed paired analysis to minimize subject numbers
Both lenses (OK and GP) were fabricated from the hyper-Dk
without sacrificing statistical power, and it limited the risks of Boston XO2 material (hexafocon B, Dk 141 ISO/Fatt units; Bausch
attrition bias from study dropouts. The crossover study & Lomb Boston, Wilmington, MA). Nominal center thickness for
design provided efficient confirmation of study outcomes the OK lenses was 0.23 mm, and 0.17 mm for the GP lenses,
over 2 consecutive 6-month lens-wearing periods. giving nominal central Dk/t of 61 and 83 Dk/t units, respectively.
The OK lens was supplied with a purple handling tint, and the GP
lens had a light blue handling tint.
Methods Before the commencement of the study, OK lenses were fitted
to both eyes according to the manufacturer’s recommended pro-
This 12-month study used a prospective, randomized, contralateral cedure. Initial lens selection was based on corneal topographic
eye crossover study design. The research conducted in this study variables including apical corneal radius and corneal sagittal height
conformed to the tenets of the Declaration of Helsinki (2008), and at a 9.35-mm chord (or 8.95 mm for A-BE lenses), as measured by
the research protocol and documentation received approval from the Medmont E-300 corneal topographer (Medmont Ltd, Mel-
the University of New South Wales Human Research Ethics bourne, Victoria, Australia), horizontal visible iris diameter, and
Committee before study commencement. All subjects and their desired refractive change. An overnight lens-wearing trial using
parents or guardians gave written consent to study participation lenses indicated by the proprietary BE lens-fitting software algo-
after the nature of the study and risks and benefits of participation rithm was conducted, and outcomes from this overnight trial were

2
 Swarbrick et al 
Orthokeratology for Myopia Control

used to refine the lens parameters to determine the appropriate OK At study commencement, subjects were dispensed an OK lens
lenses to be ordered for use in the study. for overnight wear only (with no lens wear during the day) in 1 eye
Conventional GP lenses were fitted in both eyes based on chosen at random by coin toss (the “night” lens) and a conventional
standard contact lens fitting procedures, with initial lens selection GP lens for the contralateral eye for daytime wear (the “day” lens).
based on central corneal curvature data from the Medmont Subjects were required to wear the dispensed lenses as instructed
topographer. Indicated trial lenses were inserted after application of for a 6-month period (study phase 1). Routine clinical aftercare
1 drop of topical anesthetic (Alcaine 0.5%; proxymetacaine hy- examinations were conducted after 2 and 4 weeks, or on an un-
drochloride; Alcon Laboratories, Frenchs Forest, NSW, Australia) scheduled basis as indicated clinically, or if the subject or their
to minimize reflex tearing. Slit-lamp assessment of lens centration parents had any concerns.
and movement was conducted under white light, and sodium Study variables were measured after 3 and 6 months of lens
fluorescein dye under cobalt blue lighting was used to determine wear, at a morning visit within 2 hours of awakening, and at an
the lens-to-cornea fitting relationship. Lens parameters were adjusted afternoon visit approximately 8 to 10 hours after awakening.
until satisfactory dynamic lens performance and an alignment lens- Subjects were then requested to cease lens wear for a 2- to 3-week
to-cornea fitting relationship were obtained. Over-refraction was period to allow corneal topographic recovery from the effects of
performed to determine the back vertex power of the required lenses overnight OK lens use. Corneal topography was monitored peri-
to achieve 20/25 corrected vision in each eye. odically during this time. After washout of the OK effect had been
achieved (baseline ro
0.05 mm), measurements of study vari-
Measurement Techniques ables were repeated. These measurements are noted in the Results
as both regression (Reg1) measurements, and also as baseline 2
Axial Length. The IOLMaster ocular biometer (Zeiss, Jena, Ger- (BL2) measurements for the commencement of study phase 2.
many) was used to measure axial length. This noncontact instru- Lens wear was then recommenced, but with lenseeye combina-
ment is based on infrared interferometry principles and measures tions reversed. The eye that had been wearing an overnight OK
the distance in millimeters from the apex of the anterior corneal lens for the first 6 months now wore a daily wear GP lens, whereas
surface to the retinal pigment epithelium with a reported high the previous GP lens-wearing eye now wore an OK lens for
repeatability (95% limits of agreement of 0.047 to 0.038 mm in overnight wear only.
Chinese children26). Five measurements of axial length were taken During this second phase (study phase 2), routine clinical
at each measurement session and averaged. As recommended by aftercare examinations were conducted after 2 and 4 weeks of lens
the manufacturer, for safety reasons no more than 20 repeated wear or on an unscheduled basis as indicated. Study variables were
measures were taken in any eye on the same day. measured after a further 3 and 6 months of lens wear (at 9 and 12
months into the study), at a morning visit within 2 hours of
Corneal Topography awakening, and at an afternoon visit approximately 8 to 10 hours
after awakening.
The Medmont E-300 corneal videokeratoscope was used to capture
After the completion of the full 12 months of lens wear, sub-
images of the anterior corneal surface topography, which were
jects were again requested to discontinue lens wear for a 2- to
analyzed using Medmont Studio version 5 software. Corneal
3-week period to allow recovery from the effects of OK lens wear.
topographic variables of interest included corneal apical radius of
A final set of study measurements was then obtained (noted as
curvature (ro; in millimeters), corneal asphericity (Q) over a 9.35-
regression measurements Reg2 in the Results), including axial
mm chord along the flat corneal meridian, and simulated keratometry
length, corneal topography, and objective refraction.
readings (D) along the flat and steep meridians. On each measure-
ment occasion, 3 topographic maps were captured for each eye and
the mean values for the variables of interest were calculated. Clinical Management of Subjects
Before dispensing any contact lenses in this study, subjects and
Refractive Error their parents received detailed education on lens handling, insertion
Distance objective refractive error was measured without cyclo- and removal, and lens care. Intensive hands-on instruction, a
plegia in each eye using the Shin-Nippon NVision-K 5001 autor- booklet containing detailed instructions, and a DVD showing lens
efractor (Shin-Nippon, Tokyo, Japan). Five measurements were insertion and removal techniques were provided. Lenses were not
automatically obtained from each eye and averaged on each mea- dispensed until subject competence in their own lens handling had
surement occasion. been demonstrated to the satisfaction of clinical study personnel.
Subjects were provided with a contact lens storage case and
Study Protocol solutions for contact lens care and storage, including Boston
Simplus Multi-Action solution for lens disinfection and storage,
The study protocol is summarized in Figure 1. Before Boston Advance Cleaner for surfactant lens cleaning after removal,
commencement of the study, a thorough optometric examination Sensitive Eyes Saline solution for lens rinsing before storage, and
was performed to ensure that study entry criteria were met and that Boston Rewetting Drops for in-eye lubrication as required (all
subjects were suitable for overnight OK lens wear. The OK and GP Bausch & Lomb Inc, Rochester, NY). Solutions were supplied
lenses to be ordered for wear in the study were then determined for by Bausch & Lomb (Australia) Pty Ltd (Frenchs Forest, NSW,
each subject using the fitting procedures described above. Australia). Subjects were instructed to store the OK lens during the
All subjects were then preadapted to binocular daily (open-eye) day in Simplus solution after surfactant cleaning and saline rinsing
wear of the conventional GP lenses for 2 weeks to ensure that they and to store the GP lens overnight after similar lens care steps. The
were able to successfully wear these lenses during waking hours. open (unused) well of the lens case was to be rinsed with Simplus
A minimum daily wearing time of 8 hours was required before solution followed by saline solution, then left open to air dry when
acceptance into the study. Once adaptation had been successfully not in use. Replacement lens cases were supplied every 3 months.
demonstrated, subjects were required to cease lens wear for 2 A 24-hour contact telephone number was provided in case of
weeks, and a series of baseline measurements (baseline 1 BL1) of emergencies or queries. Subjects and their parents were instructed
axial length, corneal topographic variables, and refraction was then to cease lens wear in the event of any unusual blurred vision,
performed. discomfort, or ocular redness and to contact the research team

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 Ophthalmology Volume -, Number -, Month 2014

Figure 1. Study protocol. Items in hexagons indicate study data collection visits, items in ovals indicate periods of washout (no lens wear), and items in rectangles
relate to study protocol stages including those conducted before the commencement of data collection visits. GP ¼ gas-permeable; OK ¼ orthokeratology.

4
 Swarbrick et al 
Orthokeratology for Myopia Control

immediately. Lens wear was also discouraged during ill health, persistent difficulty adapting to open-eye GP lens wear, associated
when swimming, or in the event of travel for holidays or school with noncompliance with daily GP lens wear in the control eye,
trips, particularly overseas. Subjects were required to maintain a and 2 subjects withdrew because of the inconvenience of travelling
daily diary of lens insertion and removal times, occasions of no long distances to the research facility for frequent aftercare and
lens wear, or any other events related to contact lens wear to allow data collection. One subject was discontinued because of persistent
subsequent monitoring of lens-wearing schedules. severe daytime lens adherence to the eye, accompanied by pe-
At each aftercare visit (scheduled or unscheduled) and at data ripheral staining and erosion in the GP lens-wearing eye.
collection visits, a detailed examination, including visual acuity Two subjects withdrew at the 6-month time point because of
measurement and slit-lamp biomicroscopic assessment of the time constraints and long distances of travel to the research facility.
cornea and adnexa, was performed. Fluorescein dye was instilled to Finally, data for 1 subject were discarded after scrutiny of corneal
examine corneal integrity. Temporary discontinuation of lens wear topographic maps indicated noncompliance with the study proto-
was mandated by study protocol in the event of any clinically col, with lenses being swapped randomly between the 2 eyes.
significant adverse effects of contact lens wear. Baseline biometric data for OK and GP lens-wearing eyes ob-
Binocular vision assessment was conducted with the GP lens in tained immediately before commencement of lens wear in study
1 eye (and OK-induced reshaping correction in the fellow eye) at phase 1 are presented in Tables 1 to 4. There were no significant
each aftercare visit to ensure that good binocularity was maintained differences in any baseline parameters between eyes assigned for
during the study. Relative axial length changes in the 2 eyes were OK and GP lens wear.
also inspected to estimate the induction of any significant aniso-
metropia. Study protocol mandated early termination of lens wear Axial Length
in the event of an apparent induced refractive difference between
the 2 eyes of >1.00 D. Axial lengths in the GP and OK lens-wearing eyes in the two
At discharge, all subjects were provided with a complimentary 6-month phases of the study are presented in Figure 2. For the first
pair of lenses (either OK or GP as preferred), a supply of contact 6-month period of lens wear, the baseline measurement (BL1) was
lens solutions, and referral to a contact lens practitioner of their obtained after the preadaption phase of the study. For the second
choice for continuing contact lens care. 6-month period of lens wear, the baseline (BL2) refers to axial
length measured after the midstudy washout period of no lens
wear. Changes in axial length from BL1 (study phase 1) and BL2
Data Analysis (study phase 2) are shown in Figure 3 and Table 1.
Sample size calculations conducted during study planning were Study Phase 1. In the first 6-month period of lens wear, a
based on a number of variables that were measured in this study significant overall difference in change in axial length from base-
but are not reported herein. This led to the calculation of a mini- line was found between the OK and GP eyes (F ¼ 23.927; P <
mum sample size that was substantially larger than required to 0.001). In the OK eye, axial length was significantly shorter at 3
achieve statistical power for the outcome variables (axial length, months compared with BL1 (P ¼ 0.021) and Reg1 (P ¼ 0.004).
spherical equivalent refraction, and corneal topographic variables) There were no differences in axial length change between BL1 and
that are reported herein. Post hoc power analysis with an alpha Reg1 (P > 0.99) or between the 3- and 6-month visits (P ¼ 0.751).
level of 5% indicated that, for the primary outcome variable (axial In the GP eye, there was no change in axial length during the first 3
length), a statistical power of 81.9% was achieved at the end of months (P ¼ 0.458). However, axial length became significantly
study phase 1 and 98.0% at the end of study phase 2. longer at 6 months (P ¼ 0.011) and at the Reg1 (P ¼ 0.001) visit
Data obtained at the morning visits only are reported in this compared with BL1.
article. Normality of data was assessed using the Shapiro-Wilk test Study Phase 2. After reversal of lenseeye combinations in the
before conducting parametric tests (SPSS version 21; IBM, Chi- second 6-month lens-wearing period, a significant difference in
cago, IL). Paired t tests were conducted on baseline (BL1) data. change in axial length from baseline was found between the OK
The effects of OK and GP lenses on axial length, refraction, and and GP eyes (F ¼ 40.981; P < 0.001). In the OK eye, there were
corneal topography changes or progression were assessed initially no differences in axial length change measured at the different
using linear mixed model analysis. The linear mixed model anal- study visits (P > 0.05). In the GP eye, there was an increase in
ysis was chosen to account for sporadic missing clinical data. If axial length from BL2, which became significant at 12 months
significant differences between lens types were identified with this
analysis, post hoc t tests with Bonferroni correction were then used
to compare effects between visits in eyes wearing OK and GP Table 1. Changes in Axial Length from Baseline (BL) (Phase 1,
lenses. P ¼ 0.05 was used to denote significance. and BL2; Phase 2) in Eyes Assigned to Orthokeratology (OK) and
Gas-permeable (GP) Lens Wear

Results Study Phase OK Eye GP Eye

1
Subject Demographics and Study Discontinuations 3 months 0.04
0.08* 0.02
0.06
6 months 0.02
0.09 0.04
0.08*
Of the 32 subjects who were initially recruited to participate in this Reg1 0.01
0.08 0.05
0.09*
research, a total of 26 subjects (12 female, 14 male; mean age, 2
13.4
1.9 years; age range, 10.8e17.0 years) completed the first 6 9 months 0.05
0.07 0.04
0.09
months of lens wear, and 24 subjects successfully completed 12 12 months 0.05
0.11 0.09
0.12*
months of the study. There were no significant differences in de- Reg2 0.00
0.11 0.10
0.12*
mographic or study variables at baseline for the 26 subjects who
completed 6 months of the study and the 24 subjects who
Reg ¼ regression.
completed the full 12 months of lens wear. Values are presented as mean
standard deviation (mm).
Five subjects were discontinued from the study before the *P < 0.05 versus baseline (protected post hoc paired t test).
6-month time point. Two of these subjects discontinued because of

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 Ophthalmology Volume -, Number -, Month 2014

Table 2. Objective Spherical Equivalent Refraction (mean
SD) the eye assigned for daily GP lens wear, M was significantly more
in Eyes Assigned to Orthokeratology (OK) and Gas-permeable negative or more myopic compared with BL2 at the 9-month (P ¼
(GP) Lens Wear 0.010), 12-month (P < 0.001), and Reg2 visits (P < 0.001).
However, there were no differences in M between the 9-month,
Study Phase OK Eye GP Eye 12-month, and Reg2 visits (P > 0.99).
Changes in spherical equivalent refractive error from relevant
1
baselines at completion of the two 6-month lens-wearing phases
BL1 2.43
0.98 2.39
0.93
3 months 0.19
0.94* 2.51
1.07
are presented in Figure 4. The data shown in this figure were ob-
6 months 0.11
0.91* 2.58
1.14 tained after a washout period from lens wear to allow for recovery
Reg1 2.22
1.07 2.58
1.17 from myopia correction in the OK lens-wearing eye. The period of
2 no lens wear during washout averaged 21
15 days (range, 7e46
BL2 2.60
1.21 2.22
1.10 days) after the first 6 months and 16
4 days (range, 11e29 days)
9 months 0.32
0.92* 2.39
1.05* after the second 6 months of the study. The period during which
12 months 0.31
0.97* 2.59
1.20* subjects abstained from lens wear was determined partially by a
Reg2 2.36
1.15 2.76
1.27* requirement for recovery of corneal apical radius to baseline values

0.05 mm but also was extended in some circumstances for
subject convenience (e.g., because of school vacation periods).
BL ¼ baseline; Reg ¼ regression.
Values are presented as mean
SD (D).
After both study phases, the GP lens-wearing eye demonstrated
*P < 0.05 versus baseline (protected post hoc paired t test). increased myopia relative to baseline, which reached statistical
significance (P < 0.001) only in study phase 2 (Reg2). Conversely,
the OK lens-wearing eye retained a slight hyperopic shift relative
to baseline, which failed to attain significance (P ¼ 0.636).
(P < 0.001) and Reg2 (P ¼ 0.001). Furthermore, axial length was At baseline (BL1) before commencing the study, among the 24
greater at Reg2 compared with the 9-month visit (P ¼ 0.031). subjects who completed the full 12 months of the study, there
was no difference in spherical equivalent refraction between the 2
Refractive Error eyes (GP-OK, 0.03
0.46 D). After washout at the end of study
phase 1 (Reg1), the eye that wore the GP lens was, on
Spherical equivalent refractive error (M) in the OK and GP lens- average, 0.38
0.41 D more myopic than the OK lens-wearing
wearing eyes during the 2 phases of the study are presented in eye. After crossover of lens, types, and a further 6 months of lens
Table 2. wear and washout (Reg2), the eye that had switched to the GP lens
Study Phase 1. There was a significant hyperopic shift or was now on average 0.40
0.38 D more myopic than the eye that
correction of myopia after 3 (P < 0.001) and 6 months (P < 0.001) had switched to the OK lens. Thus, a small but clinically insig-
of OK lens wear. There was no difference in M between the 3- and nificant degree of anisometropia was induced in this study (i.e.,
6-month visits in the eye assigned for OK lens wear (P > 0.99) or <0.50 D more myopia in the eye that commenced with OK lens
between BL1 and Reg1 visits (P > 0.99). There was no change in wear then switched to GP lens wear). Some of this residual
M in the GP lens-wearing eye during study phase 1 (F ¼ 2.019; anisometropia may have resulted from incomplete washout of the
P ¼ 0.119), although there seemed to be a trend suggesting some OK effect at the end of study phase 2 (as suggested by Fig 4),
myopia progression. meaning that the OK lens-wearing eye retained slightly reduced
Study Phase 2. Similar to study phase 1, there was a significant manifest myopia at the Reg2 visit.
positive shift in M in the eye assigned for overnight OK lens wear
at the 9- (P < 0.001) and 12-month visits (P < 0.001) compared Corneal Topography
with BL2. The M was similar after 9 and 12 months of OK lens
wear (P > 0.99) and between BL2 and Reg2 visits (P ¼ 0.636). In Tables 3 and 4 summarize the topographic variables of interest
every 3 months during study phases 1 and 2 in the OK and GP
eyes.
Table 3. Corneal Topography Parameters in Eyes Assigned to Study Phase 1. After 3 and 6 months of OK lens wear, there
Orthokeratology (OK) and Gas-permeable (GP) Lens Wear during was a significant increase in ro or flattening of the corneal apex and
Study Phase 1 a significant decrease or flattening of flat and steep K (all P <
0.001) compared with BL1. A significant positive shift in Q value
Group ro (mm) Flat K (D) Steep K (D) Q (toward oblate) was also measured after 3 and 6 months (both P <
0.001). No differences in ro, flat or steep keratometry (K; in
OK diopters) or Q value were found between BL1 and Reg1 (P >
BL1 7.77
0.19 43.11
1.09 44.38
1.18 0.39
0.12
0.648) or between the 3- and 6-month visits (P > 0.656).
3 months 8.21
0.26* 41.22
1.27* 42.49
1.25* 0.05
0.14*
6 months 8.18
0.30* 41.34
1.09* 42.62
1.24* 0.02
0.24*
In the GP eye, ro measured at 3 months was slightly but
Reg1 7.80
0.21 42.89
1.07 44.28
1.23 0.38
0.14 significantly increased compared with BL1 (P ¼ 0.032). At Reg1,
GP ro had significantly decreased compared with both the 3- and
BL1 7.76
0.21 43.09
1.12 44.30
1.26 0.40
0.12 6-month visits (P < 0.009). Flat K was significantly reduced at 6
3 months 7.81
0.20* 42.88
1.09 44.11
1.17 0.37
0.12 months compared with BL1 (P ¼ 0.014) but increased significantly
6 months 7.79
0.21 42.94
1.16* 44.30
1.23 0.37
0.14 at Reg1 (P ¼ 0.006). Steep K was significantly increased at Reg1
Reg1 7.75
0.22 43.10
1.18 44.57
1.32* 0.43
0.14 compared with all other visits (P < 0.05). The Q values were
significantly more negative at Reg1 compared with the 3- and
6-month visits (P < 0.003). Otherwise, ro, flat and steep K, and Q
BL ¼ baseline; Q ¼ corneal asphericity; Reg ¼ regression; ro ¼ apical values were similar between all other visits (P > 0.05).
radius of curvature.
Values are presented as mean
standard deviation. Study Phase 2. Similar to phase 1, during study phase 2 there
*P < 0.05 versus baseline (protected post hoc paired t test). was a significant increase in ro or flattening of the corneal apex, a
significant decrease in flat and steep K, and a significant positive

6
 Swarbrick et al 
Orthokeratology for Myopia Control

Figure 2. Axial length in gas-permeable (GP; grey) and orthokeratology (OK; black) eyes during study phases 1 and 2. Dashed lines indicate periods of no lens
wear. Error bars represent standard error. BL ¼ baseline; M = month; Reg ¼ regression.

shift in Q values (all P < 0.001) after 3 and 6 months of OK lens Clinical Observations
wear (at the 9- and 12-month time points in the study) compared
with BL2. No difference was found between BL2 and Reg2 visits Clinical observations of interest during this study, such as transient
(P > 0.172) or between the 9- and 12-month visits (P > 0.99) for and reversible unilateral ptosis in the conventional GP lens-wear-
ro, steep K, and Q values. However, flat K values measured at ing eye, and issues relevant to managing GP and OK lens wear in
Reg2 were slightly flatter compared with BL2 (P ¼ 0.046). children, including analyses of lens replacements and breakages,
In the GP eye, compared with BL2 there was a slight but sig- unscheduled episodes of lens wear cessation, and lens-wearing
nificant steepening of ro at 12 months (P ¼ 0.026), which persisted diary entries, will be presented in detail elsewhere.
at Reg2 (P < 0.001). This slight corneal steepening was also noted
at Reg2 for steep K (P ¼ 0.008) and was accompanied by a
negative shift in Q values (P ¼ 0.014). At all other visits, ro, steep Discussion
K, and Q values were similar (P > 0.05). There was no change in
flat K in the GP eye in study phase 2 (F ¼ 2.059; P ¼ 0.114).
These data demonstrate clinically significant changes from By using a contralateral-eye crossover study design, this
baseline in apical corneal radius, flat and steep K values, and Q in clinical study clearly demonstrated a slower rate of axial eye
the OK lens-wearing eyes only, confirming that an OK effect was growth and myopia progression during overnight OK lens
achieved during overnight wear of the reverse geometry lenses wear compared with daytime wear of conventional rigid GP
during both study phases 1 and 2. In the eye assigned for GP lens contact lenses over 2 consecutive 6-month lens-wearing
wear, although sporadic statistically significant changes in corneal periods. Analysis of corneal topographic changes during
topography were found during both study phases, these were not the 12-month study confirmed the presence of a corneal
clinically significant. reshaping effect in the OK lens-wearing eyes, and objective
refraction also confirmed the myopia correction effects of the
corneal reshaping induced by overnight OK lens wear.
Table 4. Corneal Topography Parameters in Eyes Assigned to Changes in objective refraction after cessation of lens wear
Orthokeratology (OK) and Gas-permeable (GP) Lens Wear during and regression of OK lens-induced corneal topographic effects
Study Phase 2 were consistent with the different rates of axial length growth
in the 2 eyes. The myopia control effects of OK lens wear were
Group ro (mm) Flat K (D) Steep K (D) Q
convincingly supported by the strong crossover effect when
OK lenseeye combinations were reversed in the second 6-month
BL2 7.74
0.23 43.14
1.22 44.64
1.35 0.43
0.14 phase of lens wear, resulting in complete crossover of axial
9 months 8.13
0.24* 41.55
1.15* 42.93
1.34* 0.09
0.15* growth rate differences between the study and control eyes.
12 months 8.16
0.24* 41.37
1.07* 42.76
1.23* 0.08
0.17*
Reg2 7.81
0.23 42.85
1.20* 44.31
1.32 0.37
0.12 There have been a number of previous reports demon-
GP strating clinically and statistically significant myopia control
BL2 7.80
0.21 42.90
1.11 44.31
1.27 0.38
0.14 effects with overnight OK lens wear.16e23 All of these
9 months 7.78
0.21 43.01
1.19 44.43
1.37 0.37
0.10 studies utilized the conventional clinical study protocol of
12 months 7.77
0.20* 43.00
1.16 44.33
1.24 0.40
0.14 comparing 1 group of subjects wearing OK lenses with a
Reg2 7.75
0.21* 43.05
1.14 44.59
1.30* 0.43
0.13* separate matched control group of subjects wearing spec-
tacles16,18e23 or conventional soft contact lenses.17 Only
BL ¼ baseline; K ¼ keratometric; Q ¼ corneal asphericity; Reg ¼ recently have the results from truly randomized clinical trials
regression; ro ¼ apical radius of curvature. been reported20,22,23dmost early studies either used histor-
Values are presented as mean
standard deviation.
*P < 0.05 versus baseline (protected post hoc paired t test). ical controls16,17 or allowed subject self-selection into study
or control groups. Typically, these previous studies have

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 Ophthalmology Volume -, Number -, Month 2014

Figure 3. Changes in axial length from baseline (BL) 1 (phase 1, and BL2; phase 2) in gas-permeable (GP; grey) and orthokeratology (OK; black) eyes
during study phases 1 and 2. Dashed lines indicate periods of no lens wear. Error bars represent standard error. M ¼ month; Reg ¼ regression.

been conducted over a 2-year period of lens wear, although The novel study design used in the current research avoids
an article reporting 5 years of OK lens wear has been many of these difficulties by comparing the axial growth rate
recently published.21 Although most studies have included in the 2 eyes of the same subject simultaneously wearing 2
only subjects with low to moderate myopia, 2 recent studies different lens types. Because of the use of the 2 eyes of the
investigated the effects on myopia progression of astigmatic same subject for study and control conditions, paired statistics
OK22 and partial OK correction in high myopia.23 The can be used to reduce significantly the required subject
myopia control effects of OK reported by previous studies numbers while retaining statistical power, and dropouts from
have ranged between 32% and 63% compared with controls. the study do not affect the within-subject matching of study
The study design used in previous OK myopia control and control conditions. We were also able to apply random-
studies typically requires quite large numbers of subjects, ization in terms of which eye wore the OK lens and which
and these studies are expensive and time-consuming to wore the GP lens. A further advantage of our study was our
conduct. Difficulties can arise because of study dropouts, ability to monitor crossover effects by repeating the 6-month
which may confound subject matching between study and lens-wearing period with lens-eye combinations reversed.
control groups. More important, the risk of bias in study Although we recorded a moderate dropout rate of 25%, the
outcomes can be exacerbated if the reasons for dropout risk of bias arising from these dropouts is minimized because
differ markedly between treatment and control groups.25 For of the reasons for attrition. Of the 8 subjects who discontinued
example, when subjects drop out of OK because of poor after study enrollment, 4 withdrew because of inconvenience
refractive outcomes, lens discomfort, or adverse events, this in attending study visits, 3 because of lens-related problems in
clearly has implications for the overall clinical efficacy of the control eye (2 because of persistent discomfort and 1
this treatment for myopia control. owing to an adverse event), and data from 1 subject were
excluded from analysis because of noncompliance. Accord-
ing to the Cochrane Handbook, these reasons for dropout
carry a low risk of introducing attrition bias.25 Furthermore,
because of the contralateral eye study design, these drop-
outs were balanced between treatment and control eyes.
Nevertheless, the application of this novel study design
was not without its challenges, requiring excellent cooperation
from both subjects and parents to maintain compliance with
the complex study protocol. This compliance was monitored
through use of a daily lens-wearing diary and was reinforced
by using different lens tints for the 2 different study lenses,
by careful subject selection and education on study protocol,
and through regular communication with subjects and par-
ents. That these strategies worked in maintaining compli-
ance with the protocol is clearly reflected in the outcome
that data from only 1 subject had to be rejected from anal-
Figure 4. Change in objective spherical equivalent refraction (M) from ysis because of noncompliance.
baseline after a washout period of no lens wear at the end of study phases 1 Previous studies of myopia control by OK lens wear have
(Reg1) and 2 (Reg2). Asterisk indicates statistically significant change from used either spectacles or soft contact lenses as the control
baseline. Error bars represent standard deviation. D ¼ diopter; GP ¼ gas- condition. The use of soft contact lenses is justified based on
permeable; OK ¼ orthokeratology. previous research that has demonstrated no myopia control

8
 Swarbrick et al 
Orthokeratology for Myopia Control

effect with this lens-wearing modality.27 In our study, we because of the small number of subjects, and the con-
chose to use conventional rigid GP lenses for daytime wear as founding effects of the contralateral eye study design.
our control condition. This was based on the findings from There has been much speculation on the possible mech-
previous research that such lenses do not provide a myopia anisms underlying the demonstrated effect of OK lens wear
control effect when fitted in corneal alignment.28 The choice on myopia control. The most strongly supported hypothesis
was also made for logistical reasons in terms of simplifying is based on the animal work by Smith et al,14 which
the lens care regimen and because rigid contact lens daily demonstrated that the peripheral retina has a greater influence
wear has been demonstrated to carry the least risk of com- on axial eye growth in the developing eye than previously
plications such as microbial keratitis.29 appreciated. Induction of hyperopic defocus on the peripheral
The challenge of using this modality was the possible dif- retina in animal models induces axial eye growth and the
ficulty of subjects adapting to rigid lens wear in the open eye. development of myopia, whereas myopic defocus on the
Walline et al30 previously reported that children show excel- peripheral retina induces reductions in the rate of eye growth
lent adaptation to rigid lens wear, with almost 80% of children and hyperopia.14,35 In humans, it has been demonstrated that
able to wear rigid lenses successfully for up to 40 hours per myopes typically experience relative hyperopic defocus
week. We addressed this issue by requiring potential subjects along the horizontal retinal meridian when wearing conven-
to preadapt to daily wear of bilateral rigid lenses before formal tional myopic correction in the form of spectacles36 or con-
enrollment into the study to ensure that they would be able to tact lenses.37 However, corneal reshaping after OK lens wear
wear these lenses comfortably during the study period. Despite has been shown to induce myopic defocus on the peripheral
this, 2 subjects who were enrolled dropped out subsequently retina.24 It is speculated that this may be the mechanism
because of persistent discomfort in the GP lens-wearing eye. underlying the myopia control effects of OK lens wear.
Nevertheless, our experience has confirmed the earlier ob- Other optical effects such as spherical aberration, which
servations of Walline et al; we found that the child subjects in is increased during myopic OK,38 may also play a role in the
our study on the whole were satisfied with the comfort of the myopia control effects of OK. Clearly, further research is
“day” lens. This may also have been influenced by the fact that needed to clarify the relative importance of these induced
lens wear was unilateral, which may have ameliorated optical effects and other factors in myopic development,
discomfort. There were no reports of persistent discomfort such as genetics and environment, in the progression of
with the OK lenses, which were worn only in the closed eye. myopia in children.2
There have been previous reports of contralateral or The results of our research give rise to some important
sympathetic effects of lens wear in 1 eye modifying the ef- questions. Axial length seemed to shorten in the first 3
fects seen in the fellow eye. Contralateral effects on the months of OK lens wear, and this effect was apparent in
corneal edema response31 and epithelial cell proliferation32 both phases of the study. The amount of axial shortening
have been reported, although others have found no contra- averaged about 39 microns. Part of the explanation of this
lateral effect on corneal thickness, oxygen uptake, or endo- apparent axial shortening lies in the known effect of OK
thelial bleb response,33 suggesting that such sympathetic lenses on central corneal epithelial thickness. Alharbi and
effects are quite subtle. Although the contralateral eye study Swarbrick39 reported an average of 19 microns of central
design used in this research provided many advantages, there corneal thinning after 3 months of overnight OK lens wear
is a possibility that contralateral effects may have confounded in young adult subjects who achieved an average refractive
the data. If this were the case, it would be expected that this error correction of þ2.63 D. Our cohort of child subjects
would reduce the difference in response between the 2 eyes achieved an average refractive correction of þ2.25 D after 3
rather than exaggerate the difference in response. Although months of OK lens wear, which corresponds with approxi-
we concede that the myopia control differences between the mately 16 microns of central corneal thinning. Thus, this
eyes may be underestimated because of this possible well-established effect of OK lens wear explains about one
confounder, the fact that significant differences in axial half of the apparent axial shortening found in this study in
growth rates were found suggests that contralateral effects the first 3 months of OK lens wear.
were minimal in their influence on study outcomes. The explanation for the other component of axial short-
Although on average the OK lens-wearing eye showed ening is more speculative. Read et al40 recently demon-
significantly less axial elongation in both phases of the study strated a rapid onset of choroidal thickening in humans
compared with the GP lens-wearing eye, there were sig- exposed to myopic defocus in the short term. This is anal-
nificant individual differences in response. Some individual ogous to the choroidal thickening response that has been
subjects showed no axial length growth, whereas others noted in many animal species during recovery from expo-
showed strong axial growth with OK lens wear, as indicated sure to a myopiogenic stimulus such as defocus or form
by the measures of variance presented in the Results. The deprivation.41 We speculate that some of the short-term
reasons for this variability in response are currently unclear. axial shortening found in our study may represent choroidal
Santodomingo-Rubido et al34 suggested that myopia control thickening induced by a reduction in myopiogenic stimulus,
with OK is influenced by a number of factors, including which may result from OK lens wear. The IOLMaster bio-
patient age and gender, age at onset, degree and progression meter used in our study measures axial length from the apex
rate of myopia, and various anatomic features, including of the cornea through to the front of the retinal pigment
corneal power and shape, anterior chamber depth, and iris epithelium. Any choroidal thickening would move the retinal
and pupil diameter. Analysis of the influences of baseline pigment epithelium forward, giving rise to an apparent
characteristics on the efficacy of OK in our study is limited shortening of the eye. We did not monitor choroidal

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 Ophthalmology Volume -, Number -, Month 2014

thickness in our study, so are not able to provide any evi- elongation be optimized for all myopic children to improve
dence to support this hypothesis. Clearly, further research is the overall efficacy of this modality for myopia control?
needed to shed light on this possible mechanism.
Acknowledgments. The authors acknowledge the contributions
Another interesting observation from our study was the of Professor Dwight H. Cavanagh (University of Texas South-
apparent rapid progression of eye growth in the GP lens- western Medical Center, Dallas, TX), Professor Minas Coroneo
wearing eye in study phase 2 compared with the rate of eye (Department of Ophthalmology, University of New South Wales,
growth in the contralateral GP lens-wearing eye in study Sydney, Australia), and Professor Fiona Stapleton (School of
phase 1 (Fig 3). Axial length change in the GP lens-wearing Optometry and Vision Science, University of New South Wales,
eye during phase 2 was approximately double the change Sydney, Australia), who provided guidance and support during the
found during phase 1, and this difference reached statistical conduct of this study, including acting as a Data Safety Monitoring
significance (P ¼ 0.043). At the start of study phase 2, the GP Panel. The contributions of Associate Professor Barbara Junghans
lens-wearing eye had been wearing an OK lens for 6 months, during the study design phase are also gratefully acknowledged.
and its axial growth had been inhibited. We speculate that the
more rapid eye growth in phase 2 in this study may represent
a “rebound” effect, such as that recently demonstrated in References
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Footnotes and Financial Disclosures

Originally received: March 5, 2014. Lens Pty Ltd. Contact lenses were supplied on a complimentary basis by
Final revision: September 4, 2014. Capricornia Contact Lens, and Bausch & Lomb (Australia) (Frenchs Forest,
Accepted: September 20, 2014. Sydney, Australia) supplied all contact lens solutions. The sponsors or
Available online: ---. Manuscript no. 2014-347. funding organizations had no role in the design or conduct of this research.
1
School of Optometry and Vision Science, University of New South The authors have no proprietary or commercial interest in any materials
Wales, Sydney, Australia. discussed in this article.
2
Department of Optometry and Vision Science, King Saud University, This research was registered as a clinical trial with the Australian and New
Riyadh, Saudi Arabia. Zealand Clinical Trials Registry (ANZCTR) in January 2008, with refer-
Presented at: The Association for Research in Vision and Ophthalmology ence number CTRN12608000007336.
Annual Meeting, May 2011, Fort Lauderdale, Florida; The Association for Abbreviations and Acronyms:
Research in Vision and Ophthalmology Annual Meeting, May 2010; The BL ¼ baseline; D ¼ diopters; GP ¼ gas permeable; M ¼ spherical
British Contact Lens Association Annual Meeting, May 2011, Manchester, equivalent refractive error; OK ¼ orthokeratology; Q ¼ corneal aspher-
United Kingdom. icity; ro ¼ apical radius of curvature; Reg ¼ regression.
Financial Disclosure(s): Correspondence:
Supported by the Australian Research Council’s Linkage Grant Project Helen A. Swarbrick, PhD, School of Optometry and Vision Science,
scheme, with industry collaborators Bausch & Lomb Boston (Wilmington, University of New South Wales, UNSW, Sydney, NSW 2052, Australia.
MA), BE Enterprises Pty Ltd (Brisbane, Australia), and Capricornia Contact E-mail: [email protected].

11