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A randomised clinical trial to assess the effect of a dual treatment on myopia progression: The Cambridge Anti-Myopia Study Running head – The Cambridge Anti-Myopia Study Peter M Allen 1,2 Hema Radhakrishnan 2,3 Holly Price 1,2 Sheila Rae 1,2 Baskar Theagarayan 1,2 Richard I Calver 1,2 Ananth Sailoganathan 4 Keziah Latham 1 Daniel J O’Leary 1,2 1 Vision and Eye Research Unit, Postgraduate Medical Institute, Department of Vision and Hearing Sciences, Anglia Ruskin University, Cambridge, UK 2 Vision Cooperative Research Centre, Sydney, Australia 3 Faculty of Life Sciences, University of Manchester, Manchester, UK 4 School of Optometry, National Institute of Ophthalmic Sciences, Tunn Hussein Onn Eye Hospital, Petaling Jaya, Malaysia Word count: 3343 Correspondence to: Peter M Allen Department of Vision and Hearing Sciences Anglia Ruskin University East Road Cambridge United Kingdom CB1 1PT 0044 845 1962687 e-mail: [email protected] Key words: Myopia, Lag of accommodation, Facility of accommodation, Spherical aberration Abstract Purpose: To evaluate the effect of a dual treatment modality for myopia, by improving accommodative functions, on myopia progression. Methods: A double blind randomised control trial was conducted on 96 subjects. The treatment modality for the trial employed custom designed contact lenses which control spherical aberration in an attempt to optimise static accommodation responses during near-work, and a vision-training programme to improve accommodation dynamics. Myopia progression was assessed over a 2 year period using cycloplegic autorefraction and biometry. Results: The mean progression was found to be -0.33D over the 2 years of the study. There was no interaction between contact lens treatment and vision training treatment at 24 months (p=0.72). There was no significant treatment effect of either Vision Training or Contact Lens Spherical Aberration control on myopia progression. Conclusions: This study is unable to demonstrate that the progression of myopia can be reduced over a 2 year period by either of the 2 treatments aimed at improving accommodative function. Neither treatment group (contact lens or vision training) progressed at a slower rate over the 2 years of the study than did the appropriate control group. Introduction The prevalence of myopia is on the increase in some populations.1-3 Both environmental and genetic factors are likely to be involved.4,5 Abnormal accommodation function has been identified as myopigenic, possibly by producing hypermetropic retinal image defocus.5-7 Mutti et al.8 suggested that myopia produces the accommodative abnormalities possibly due to an effect of eye growth on the ciliary apparatus. Alternatively, some of the anomalous accommodative factors may be related to the low sensitivity to blur exhibited by myopes, and may still be myopigenic.9 Attempts to arrest myopia progression in children using multifocal spectacles have met with limited success.10-12 The COMET study12 showed that multifocal lenses slowed myopia progression during the 1st year but not thereafter. Unfortunately no information was gathered about the effect of the multifocals on accommodation through the study. We have shown that both a short13 and relatively longer term14 reduction in lag of accommodation can be produced when customized contact lenses are used to induce controlled amounts of negative spherical aberration in young myopic individuals. Gambra et al.15 also demonstrated a reduction in the lag of accommodation with induced negative spherical aberration and an increase with induced positive spherical aberration and coma. Reduced accommodative facility is associated with both myopia16-18 and myopia progression.7 Accommodative response times to step stimuli are longer in myopia.19 Increased lag of accommodation and reduced accommodative facility are independently associated with myopia progression in young adults.7 Accommodative functions can be improved through vision training20-25 however we could find no robust placebo-controlled studies that assessed the effectiveness of vision training on reducing myopia progression. The Cambridge Anti-Myopia Study is designed to evaluate a dual treatment modality for myopia by improving the two accommodative functions identified as being independently associated with myopia progression.7 The study uses aberration controlled contact lenses to reduce the lag of accommodation 13,14 and vision training to improve accommodative facility.14,26 We hypothesise that these interventions will reduce myopia progression, so the main outcome measures of our study are the progression of myopia assessed by cycloplegic auto-refraction, and axial length increase determined by partial coherence inferometry. In addition, the study aims to understand the interaction between accommodative function and myopia progression. Because of the great complexity of the data-set collected, and the statistical analysis needed to locate factors associated with myopia progression, the data from the Cambridge Anti-Myopia Study is presented in two separate papers. This paper reports the results of the clinical trial on myopia progression. Methods The treatment modality for The Cambridge Anti-Myopia Study employs custom designed contact lenses which control spherical aberration in an attempt to optimise static accommodation responses (i.e. reduce the lag of accommodation) during near-work, and a vision-training programme to improve accommodative facility. A factorial trial design was used to test the efficacy of the two independent treatments simultaneously. Participants were allocated to one of four treatment groups: 1, altered spherical aberration and vision training; 2. vision training only; 3. altered spherical aberration only; 4. no change to spherical aberration and no vision training. Study Design Participants Participants were recruited over an eight month period and were in the age range of 14-22 years. Inclusion criteria for The Cambridge Anti-Myopia Study were: Age at enrolment: 14-22 years Spherical equivalent cycloplegic refractive error: -0.75 to –10.00 Dioptres Astigmatism: 0.75 Dioptres or less Log MAR visual acuity with spectacle correction: 0.00 or better in each eye No heterotropia or uncompensated heterophoria (as assessed by cover test) Free of ocular pathology Free of systemic pathology which may affect myopia progression Zero or positive ocular spherical aberration at distance Able and willing to wear soft contact lenses for the duration of the trial No previous participation in myopia control studies Our sample size calculation was based on a previous study we conducted on a population similar to the older half of the target population of the present study,7 where myopia progression was -0.25D per annum on average with a SD of 0.3. For a treatment effect of 0.3D, p=0.05, power = 0.90, we needed a minimum cohort of 96 participants divided between treatment and control groups. We felt that a treatment effect of 0.30D would be clinically significant. We publicised the trial through UK public media. Two hundred and twenty volunteers attended a baseline assessment visit and 147 were suitable for enrolment into the study between May 2005 and February 2006. The remainder were excluded due to unsuitable refractive error, presence of negative spherical aberration, amblyopia, corneal pathology or unwillingness to proceed. A further five participants were unable to proceed due to inability to handle the contact lenses. Participants (and their care givers if applicable) were told the objectives of the project, and that they would be fitted with contact lenses for normal daily wear, but that they might or might not be getting the experimental treatment. A condition of enrolment was that the participant would accept any of the treatment modalities and that they would not know whether they were assigned to a treatment or control group during the course of the trial. Participants gave informed consent for taking part in the study, which followed the tenets of the Declaration of Helsinki and was approved by the Anglia Ruskin University Ethics Committee. Baseline spherical aberration data were collected from both eyes before cycloplegia and without a refractive correction in place. Data from the participant’s right eye were used for all analyses except accommodation measurements, which were taken from the left eye (occluded with an infra-red transmitting filter) while the right eye was viewing the target. The baseline levels of spherical aberration ranged from 0 to +0.225 μm. All measures of spherical aberration throughout the study were referenced to a 5-mmdiameter pupil. Allocation masking procedure Participants were stratified according to age, gender, cylindrical refractive error and spherical refractive error as shown in Table 1. One experimenter, who was unmasked, allocated participants to groups. Participants were referred to this experimenter by others who were enrolling participants in the trial. The experimenter allocating participants did not take part in any of the masked measurements, and was available to look at treatment regimes with Vision Training, and clinical issues relating to contact lens aftercare. The masked experimenters had no information about the way individual participants were allocated to treatment groups, and remained masked for the duration of the study. When a participant was the first (and third etc.) member of a block, they were assigned by coin-toss to the control or treatment groups, and the second (and fourth etc.) member of a block were assigned to the alternate group. Therefore, all participants wore contact lenses, either treatment or control, for the duration of the study. In order to mask the participants with regard to the treatment that they were getting, the participants were told that, in addition to wearing contact lenses, there were a range of possible things they might be required to do (including vision training), but this was not described in a way where they would see themselves as being in another treatment group or not for the purposes of the clinical trial. However, we did not have a placebo control for the vision training group. We believe that these measures, together with the participant masking procedures effectively fulfil the CONSORT requirements for a double masked randomised clinical trial.27,28 ____________________________________________________________ Insert Table 1 about here Treatment design (a) Altered spherical aberration Soft contact lenses were designed to alter ocular spherical aberration of each eye in addition to correcting the spherical equivalent axial refractive error. The front surface curvature was calculated using paraxial optics to correct the axial refractive error. The spherical aberration of the lens was manipulated by altering the eccentricity value of the front surface of the lens. The contact lenses were designed to alter the existing fourth order spherical aberration of the patient to -0.1μm (referenced to a 5-mm diameter pupil) while maintaining the appropriate paraxial correction. Theagarayan et al.13 demonstrated that altered spherical aberration can influence the slope of the accommodation response curve. This study showed that added positive spherical aberration significantly depressed the accommodative response slope, whereas, negative spherical aberration, at least up to -0.2 microns, enhanced it. The optimum improvement in the accommodative response slope was reached with (eye + contact lens) spherical aberration levels of -0.1 microns in an unaccommodated state. Spherical aberration of -0.1 microns for a 5mm pupil diameter will equate to 0.137D.mm-2 and therefore approximately 0.86D at the edge of a 5mm pupil when calculated using the following equation 29: Spherical aberration D.mm -2 24 5 0 C4 r4 (Equation 1) 0 where C4 is the spherical aberration coefficient measured in microns, and the r is the pupil radius measured in millimetres. In equivalent dioptric terms, spherical defocus of -0.11D would produce the same wavefront variance as -0.1 microns of spherical aberration when calculated using the following equation30: C 40 M 4 3 2 r (Equation 2) 0 where M is the equivalent spherical defocus in dioptres, C4 is the spherical aberration coefficient measured in microns, and the r is the pupil radius measured in millimetres. The spherical aberration of the control group lenses was designed to have zero spherical aberration in the contact lenses regardless of the measured spherical aberration level of the eye. A ray tracing program was used to calculate the required surface parameters of the contact lenses. These individually customized contact lenses were manufactured by UltraVision CLPL specifically for this study. All lenses were made of 58% HEMA based material. The contact lenses were fitted such that the movement on blink was approximately 0.25mm. Because this small movement of the lens during blink is likely to induce transient coma-like aberration, the aberrations with these contact lenses were measured only after the lens settled in the centred position. The aberrations in the contact lenses were assessed by measuring the total aberrations of the eye after fitting the contact lens to the patient. Both the treatment and control group contact lenses were worn at least 10 hours per day. (b) Vision training The vision training regime consisted of lens flipper exercises 31 using a +2.00D/-2.00D flipper at 40cm. The participants were instructed to complete the training whilst wearing their contact lenses. The target was a grid of N6 sized letters. The participants were instructed to: Use the block of letters provided for this exercise. Keep the page at approximately 40 cm and in good light. Look at the first letter of the block through one side of the flipper, and try and make it clear and sharp. As soon as it is clear, change to the other side of the flipper and make the next letter clear, as quickly as possible. Keep flipping as soon as the letters become clear. Do this exercise with the right eye only for 3 minutes, then the left eye only for 3 minutes, then both eyes together for 3 minutes. Accommodative facility has been shown to be independently correlated with myopia progression.7 Accommodative facility training was used in CAMS following work by Allen et al.26 that demonstrated an improvement in accommodative facility rates, both at distance and near, following three sessions of 15 minutes near accommodative facility training on three consecutive days. The improvements in facility rates exhibited were analysed further, using objective data and showed an improvement in the time constants of accommodation and disaccommodation during distance and near fixation. The exercises were performed for 18 minutes per day for up to six weeks. The purpose of the vision training program in The Cambridge Anti-myopia Study was to increase accommodative facility rates. The positive accommodative response times for distance facility have been shown to be significantly longer in myopia than in emmetropia.17 We have previously confirmed that the treatment for accommodative facility is effective. Both distance and near facility rates in the vision training treatment group improved significantly from the baseline values and significantly more than in the control group. Both the positive response times and the negative response times for distance and near accommodative facility were significantly shortened at 3 months when compared with the baseline visit.14 There was a wide range of baseline accommodative facility values hence a goal orientated approach was used. Participants were to continue with the vision training until a minimum value of 25 cycles per minute was achieved; this is an ambitious target considering normal values published by Zellers et al.32, however, were possible based on established normal values for dynamic accommodation responses.33 Participants were given verbal and written instruction for the vision training and kept a log of training sessions and achievement. The training was conducted at home with the log books checked for training compliance by an unmasked examiner. The participants were instructed to wear their contact lenses during vision training. Procedures Aberration measurement The monochromatic wavefront aberration function of the eyes was measured using the Complete Ophthalmic Analysis System (COAS) (Wavefront Sciences, Albuquerque, USA) with the participants viewing a distant target. Aberration measurements obtained from 3 consecutive readings over a pupil diameter of 5mm were averaged in the format recommended by the Optical Society of America.34 Subjective refraction Subjective refraction was performed before cycloplegia to an accuracy of 0.12D. Trial lenses were placed in a trial frame at a vertex distance of 12mm. The starting point was the objective refraction obtained from the COAS aberrometer. The subjective monocular refraction included determination of the spherical power, cylindrical power and axis of the refractive error for both eyes. The end point criterion was the maximum plus power consistent with best visual acuity and was confirmed with the +1.00D blur test. The near point of convergence (using a linear target and measured in centimetres) and the amplitude of accommodation (using N5 print and measured in dioptres) were measured with the subjective refraction in place. Accommodation Function Assessment Details of these measurements can be found in Allen et al.14 In brief, accommodative response amplitudes were measured with an open field, infrared Shin Nippon SRW 5000 auto-refractor.35,36 Measurements were obtained from the left eye which was effectively occluded with an infra-red transmitting filter (Kodak Wratten 88A), whilst the right eye viewed the targets. For each accommodative demand a series of five readings was taken from the left eye, and the average calculated. At baseline the accommodative stimulus values were adjusted to take account of ocular accommodative demand as the participants’ refractive errors were corrected with trial lenses. 5 At all subsequent visits the participants wore their contact lenses, with any over-refraction corrected with trial lenses, during measurement of accommodative function. (a) Monocular accommodative response amplitude to targets in real space. Targets were presented in real space at distances of 6.00m, 0.40m, 0.33m and 0.25m. For 6.00m, the target consisted of a row of 6/7.5 Snellen letters. For the remaining distances, the target consisted of a block of words of N5 size type. The targets were presented in order of decreasing distance. (b) Accommodative convergence to accommodation response ratio. The subjective refraction of both eyes was placed in a trial frame for these measurements at baseline, and any over refraction placed over CAMS contact lenses at subsequent visits. Jiménez et al.37 showed no significant difference in accommodative response measured through lenses compared to contact lenses. The Shin Nippon auto-refractor was used to measure the accommodative response amplitudes (from the left eye) while concurrent vergence measurements were taken using a near Howell-Dwyer phoria card, positioned at 0.33m. The participants were asked to view the numbers on the near Howell-Dwyer card keeping them clear at all times. A 6Δ base-up prism was then placed before the right eye to dissociate the eyes. Five consecutive measures of the accommodative response amplitude were made with the participants noting the position that the arrow from the top scale of numbers pointed to on the bottom scale of numbers at the time of measurement. The magnitude, to the nearest 0.5Δ and the direction of the heterophoria were recorded. The procedure was repeated using the near Howell-Dwyer card with supplementary lenses of power +2.00D, +1.00D, -1.00D and -2.00D added binocularly to the subjective refraction. With each change of lenses, the participant was asked to refocus the numbers on the tangent scale as accurately as possible. Since there is measurement error and resulting variability in both the accommodation and convergence tests when measuring the response AC/A ratio the slope of the principal axis was calculated.38,39 (c) Monocular accommodative facility The accommodative facility was measured at 6.00m and 0.40m for the right eye only with semi-automated lens-flippers interfaced with a computer. The software incorporated a 60 second timer and recorded the time between the flips. Participants who were unable to clear the target during the 60 second testing time had a facility rate of zero recorded. The positive response time in this situation was recorded as 60,000ms, although the true positive response time may have been longer than this. No negative response time was recorded for these participants. During the measurement of distance and near accommodative facility the negative lens was always presented first. Accommodative facility at 6m was measured using a Plano/–2.00D lens combination with the participant viewing 6/7.5 letters, while at 0.40m an N6 target was viewed through a flipper consisting of +2.00D/-2.00D lens combination. The effect of the negative lens on the target was demonstrated to the participants but no other training was given prior to measurement. Distance accommodative facility was measured before near facility. Cycloplegic auto-refraction The refractive error of both eyes was determined following cycloplegia with two drops of Tropicamide Hydrochloride 1% (Minims; Chauvin) in each eye at five minute intervals. Objective measurement was made with a Nidek AR600-A auto-refractor40 using a series of five readings per eye. The study protocol specified that the auto-refractor readings be obtained 25 minutes after the first drop of Tropicamide was instilled. Cycloplegic ocular biometry Ocular dimensions of both eyes were measured under cyloplegia using an IOL Master (Zeiss Humphrey, CA, USA). Five measurements of axial length were taken and the mean was calculated. Data storage Completed data records for each visit were stored securely and were not available to the masked examiners. Clinical care records contained no information regarding the treatment assignments or data from the baseline or follow-up visits. One unmasked examiner, who allocated vision training exercises, had access to data (apart from refractive error) from previous visits. Schedule of visits The schedule of visits is shown in Table 2 ______________________________________________________________ Insert Table 2 about here Lens replacement Contact lenses were replaced at least once a year for all participants. In most cases lenses were replaced more frequently than this. Criteria for replacement were: refractive error change of 0.25 or greater; lens loss or damage; clinical evidence of lens soiling. Statistical Analyses Two way Analysis of Variance (ANOVA) was used to assess whether there were any significant differences in the outcome measures including progression of myopia and axial length changes between treatment groups. Results Table 3 shows the baseline characteristics of the participants in each of the 4 treatment groups. There were no statistically significant differences in any ocular characteristics between the 4 groups (p>0.05) ______________________________________________________________ Insert Table 3 about here Clinical performance and compliance Both high and low contrast acuities have previously been shown to be significantly better in the group wearing the contact lenses with negative spherical aberration (Rae et al.41). However, although there was a statistically significant improvement in visual acuity this improvement was too small in magnitude to be of clinical significance. All participants reported at least 10 hours of contact lens wear per day. All participants in the Vision Training Treatment group reported that they completed the scheduled programme of vision training, and achieved their target facility rates. Where our measurements in the clinic revealed that their facility was below the target rate, they were asked to repeat the exercise regime again until their facility was again at the target rate. Drop outs Over the course of the trial 33% of participants dropped out of CAMS. Reasons for dropping out included dislike of the contact lens wearing modality (e.g. the lenses were not daily disposable), difficulty in travelling to data collection appointments and moving away from the trial centre. Some participants did not respond to invitations to follow-up appointments. There was no significant difference in the number of subjects who dropped out of the study from each treatment group (Chi square p=0.81) or in the gender of participants who dropped out (Chi square p=0.49). Figure 1 shows a flow diagram depicting the passage of participants through CAMS. Only participants with a full dataset are presented. ______________________________________________________________ Insert Figure 1 about here Overall outcomes of the trial on myopia progression On average the mean spherical equivalent spectacle correction of our participants’ Right eyes progressed by -0.33D (SD 0.08D) over the 2 years of the study, the same as in the Left eyes. A two way ANOVA was used to check for interaction between the two treatment regimens and change in refraction. There was no interaction between contact lens treatment and vision training treatment at 24 months (F(1,113)=0.13 p=0.72). Hence it is possible to present data from the two treatments separately. The myopia progression in the various treatment groups at 6 months intervals over the 2 year trial are shown in Figure 2. ______________________________________________________________ Insert Figure 2 about here There was no significant treatment effect of either Vision Training or Contact Lens Spherical Aberration control on myopia progression (p>0.05). Axial length increases are shown in Table 4. Axial length increased steadily over the 2 years of the study by 0.15mm (SD 0.14) in both Right and Left eyes, and the mean increases in the Right Eyes of each treatment group are shown in Table 4. There were no significant differences between axial length increases in the different groups. ______________________________________________________________ Insert Table 4 about here The best fit regression equation between axial length increase and refractive error change was: Error change (Dioptres) = -1.81 * axial length increase (mm) -0.0405, (r2=0.51). A 0.5mm axial length change would therefore result in a -0.96D change in refraction. This is comparable with other studies on myopic populations.42-45 Discussion This study is unable to demonstrate that the progression of myopia can be reduced over a 2 year period by either of the 2 treatments aimed at improving accommodative function. Neither treatment group (contact lens or vision training) progressed at a slower rate over the 2 years of the study than did the appropriate control group. The progression rate in the present study was 0.33D over 2 years. It was hypothesised that an improvement in the accommodative response function with the dual treatment modality could produce a reduction in the myopia progression rate. Plainis et al.46 suggested that lag of accommodation may be influenced by the change in spherical aberration that occurs during accommodation. Several studies47-52 have examined the changes in both spherical aberration and other higher-order aberrations during accommodation with variable results, but in general have indicated that with increasing accommodative effort, spherical aberration tends to change from an initially slightly positive value towards a negative value. An early paper from CAMS showed that at the 3-month point the dual treatments (altering SA and vision training) used were effective in modifying accommodation, the static accommodative response to targets at real distances was increased by the altered SA contact lenses and rates of accommodative facility improved with vision training.14 This change in accommodative facility did not lead to any statistically significant changes in the rate of myopia progression perhaps due to the low rate of progression seen in this cohort. This paper reports the results of the clinical trial on myopia progression; we will report the results of accommodation changes and their relationship with myopia progression in an associated paper. The participants’ mean age of about 16 years may explain the small myopic progression found in our study. Many studies select younger participants whose refractive errors are likely to change more rapidly.10-12 However, the participants in our previous study7, which served as a pilot study for this trial, demonstrated myopic progression of approximately double that of the participants despite being 3 years older. It is therefore quite possible for myopia to progress by clinically significant amounts in older participants. Interestingly, our study shows only a small drop in progression rate with age over the age-range of the study; the impact of age on myopia progression was only 0.03 D per year of age. So even for a difference in age of 5 years the difference in progression will be only 0.15D and therefore will not be clinically significant. Moreover, with older participants it would be reasonable to expect a higher amount of myopia to be present at baseline, however, when a Principal Component Analysis was applied to these data baseline spherical equivalent myopia was not significantly associated with myopic progression in this study (p>0.05) so there is no reason in the present study to think higher myopes should be treated as a separate group. We cannot entirely rule out the possibility that some accommodation therapy that improves the accuracy of focussing (either through contact lens application or vision training) may have had an effect on myopia progression, for three reasons. First, although our pilot study indicated that contact lenses with negative spherical aberration improved the accuracy of accommodation up to 1 hour after first wearing the lenses13 and that in the current investigation accommodative accuracy was maintained up to 3 months, 14 it is possible that this improvement was not sustained over the whole of the 2 year period of the study, perhaps due to adaptation to the new levels of spherical aberration. There is some evidence that the visual system adapts to induced aberrations53,54 and previous longitudinal studies of progressive addition lenses for myopia control have demonstrated a greater treatment effect during the first year compared to the second year, indicating that treatment adaptation may take place.10,12,45 Second, vision training to improve accommodation dynamics may not have produced a sustained improvement in the treatment group in comparison to the control group. Siderov55 noted that even a few measurements of accommodative facility may improve facility rates, and it may be that our regular measurements of facility rate in controls was almost as effective at improving facility as was the full vision training regime. In concordance with previous literature,20-25 the present study also shows that accommodative functions can be improved through vision training and if good compliance is established these improvements can be sustained over time. Scheimann et al.56 recently investigated the effectiveness of various forms of vision training in improving accommodative amplitude and facility in children with symptomatic convergence insufficiency and co-existing accommodative dysfunction. They reported an improvement in accommodative function in their treatment groups when compared to an office based placebo therapy. One year after the training reoccurrence of the accommodative problem had occurred in approximately 10% of their cohort. Thirdly, variations in pupil size may have altered the levels of spherical aberration to which the participants were exposed. However, the groups’ mean pupil diameters were between 5.0 and 5.2 mm (Table 3) which means that the actual spherical aberration would have been very close to the expected levels. Individual participants with particularly large or small pupils would have been exposed to various levels of induced spherical aberration. For example, we would expect participants wearing the treatment contact lenses to experience -0.1µm of fourth-order spherical aberration referenced to a 5mm diameter pupil, but this would reduce to -0.04µm for a 4mm diameter pupil and increase to -0.2µm for a 6mm diameter pupil. These values approximate to -0.55D and -1.23D respectively of spherical aberration at the edge of the pupils (Equation 1). Therefore, the wearer would still experience negative spherical aberration compared to the control group. Since pupil size varies throughout the day due to different ambient lighting and the various tasks undertaken by the individual, the aberration correction provided by the contact lenses in the CL treatment group is unlikely to have remained consistent throughout the day. We cannot control these variations during the course of a clinical trial but it is expected that the participants would still have experienced negative spherical aberration of variable amounts depending on the pupil size, and this negative spherical aberration was expected to produce more accurate accommodation in these individuals. Peripheral refraction of the eye might also be a factor influencing myopia progression.57 It is possible that the contact lenses used to alter spherical aberration might have influenced the peripheral refractive error of the eye and therefore have had some undesirable effects on this factor. Future studies controlling central and peripheral optical errors independently might be useful to understand these effects. It is also possible that peripheral refractive errors may play a more significant role in refractive error development than central optical quality.57 A recent study has shown significant changes in myopia progression when peripheral refractive errors are altered.58 In summary, our dual-treatment attempt to reduce myopia progression over a 2 year period did not show a reduction in the rate of progression of myopia in the treatment groups. While these treatment modalities were unsuccessful, this could have been because (a) of the age of the participants, (b) the treatment induced insufficient changes to accommodation or (c) the participants treatment adapted or (d) myopia progression remains unaffected by the changes in accommodation functions. Acknowledgements The authors thank Darrin Falk and Aldo Martinez (Vision CRC, Sydney) for their help in making the semi-automated flippers and the CAMS families for their enthusiastic commitment to the study. This study was supported in part by the Australian government CRC Scheme via the Vision Cooperative Research Centre. References 1. Vitale S, Sperduto RD & Ferris FL. Increased prevalence of myopia in the United States between 1971-1972 and 1999-2004. Arch Ophthalmol 2009; 127: 1632-1639. 2. Edwards MH. The development of myopia in Hong Kong children between the ages of 7 and 12 years: a five-year longitudinal study. Ophthalmic Physiol Opt 1999; 19: 286-94. 3. Zhao J, Pan X, Sui R, Munoz SR, Sperduto RD & Ellwein LB. Refractive Error Study in Children: results from Shunyi District, China. Am J Ophthalmol 2000; 129: 427-35. 4. Angle J & Wissmann DA. The epidemiology of myopia. Am J Epidemiol 1980;111: 220-8. 5. Gwiazda J, Thorn F, Bauer J & Held R. Myopic children show accommodative response to blur. Invest Ophthalmol Vis Sci 1993; 34: 690694. 6. Gwiazda J, Thorn F & Held R. Accommodation, accommodative convergence, and response AC/A ratios before and at the onset of myopia in children. Optom Vis Sci 2005; 82: 273-8. 7. Allen PM & O'Leary DJ. Accommodation functions: co-dependency and relationship to refractive error. Vision Res 2006; 46: 491-505. 8. Mutti DO, Mitchell GL, Hayes JR et al. Accommodative lag before and after the onset of myopia. Invest Ophthalmol Vis Sci 2006; 47: 837-46. 9. Radhakrishnan H, Pardhan S, Calver RI & O’Leary DJ. Unequal reduction in visual acuity with positive and negative defocusing lenses in myopes. Optom Vis Sci 2004; 81: 14-7. 10. Edwards MH, Li RW, Lam CS, Lew JK & Yu BS. The Hong Kong progressive lens myopia control study: study design and main findings. Invest Ophthalmol Vis Sci 2000; 43: 2852-8. 11. Fulk GW, Cyert LA & Parker DE. A randomized clinical trial of bifocal glasses for myopic children with esophoria: results after 54 months. Optometry 2002; 73: 470-6. 12. Gwiazda J, Hyman L, Hussein M et al. A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children. Invest Ophthalmol Vis Sci 2003; 44: 1492-500. 13. Theagarayan BB, Radhakrishnan HK, Allen PM, Calver RI, Rae SM & O’Leary DJ. The effect of altering spherical aberration on the static accommodative response. Ophthalmic Physiol Opt 2009; 29: 65-71. 14. Allen PM, Radhakrishnan H, Rae SR et al. Aberration control and vision training as an effective means of improving accommodation in myopes. Invest Ophthalmol Vis Sci 2009; 50: 5120-5129. 15. Gambra E, Sawides L, Dorronsoro C & Marcos S. Accommodative lag and fluctuations when optical aberrations are manipulated. J Vis 2009; 9: 115. 16. Jiang BC. Parameters of accommodative and vergence systems and the development of late-onset myopia. Invest Ophthalmol Vis Sci 1995; 36: 1737– 1742. 17. O'Leary DJ & Allen PM. Facility of accommodation in myopia. Ophthalmic Physiol Opt 2001; 21: 352-355. 18. Pandian A, Sankaridurg PR, Naduvilath T et al. Accommodative facility in eyes with and without myopia. Invest Ophthalmol Vis Sci 2006; 47: 4725– 4731. 19. Culhane HM & Winn B. Dynamic accommodation and myopia. Invest Ophthalmol Vis Sci 1999; 40: 1968–1973. 20. Bobier WR & Sivak JG. Orthoptic treatment of subjects showing slow accommodative responses. Am J Optom Physiol Opt 1983; 60: 678–687. 21. Ciuffreda KJ & Ordonez X. Vision therapy to reduce abnormal nearworkinduced transient myopia. Optom Vis Sci 1998; 75: 311–315. 22. Cooper J, Feldman J, Selenow A et al. Reduction of asthenopia after accommodative facility training. Am J Optom Physiol Opt 1987; 64: 430–436. 23. Liu JS, Lee M, Jang J et al. Objective assessment of accommodation orthoptics. I. Dynamic insufficiency. Am J Optom Physiol Opt 1979; 56: 285– 294. 24. Sterner B, Abrahamsson M & Sjostrom A. Accommodative facility training with a long term follow up in a sample of school aged children showing accommodative dysfunction. Doc Ophthalmol 1999; 99: 93–101. 25. Sterner B, Abrahamsson M & Sjostrom A. The effects of accommodative facility training on a group of children with impaired relative accommodation: a comparison between dioptric treatment and sham treatment. Ophthalmic Physiol Opt 2001; 21: 470 – 476. 26. Allen PM, Charman WN, Radhakrishnan H. Changes in dynamics of accommodation after accommodative facility training in myopes and emmetropes. Vision Res 2010; 50: 947-955. 27. Altman DG. Better reporting of randomized controlled trials: the CONSORT statement. BMJ 1996; 313: 570-571. 28. Moher D, Schulz KF & Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol 2001; 134: 663-694. 29. Radhakrishnan H & Charman WN. Age-related changes in ocular aberrations with accommodation. J Vis 2007; 7: 1-21. 30. Thibos LN, Hong X, Bradley A & Cheng X. Statistical variation of aberration structure and image quality in a normal population of healthy eyes. J Opt Soc Am A 2002; 19: 2329-2348 31. Griffin J & Grisham JD. Binocular anomalies: Diagnosis and vision therapy. Butterworth-Heineman, USA, 2002. 32. Zellers J, Alpert T, Rouse M. A review of the literature and a normative study of accommodative facility. J Am Optom Soc 1984; 55: 31–7 33. Campbell FW & Westheimer G. Dynamics of accommodation responses of the human eye. J Physiol 1960; 151: 285-95. 34. Thibos LN, Applegate RA, Schwiegerling JT & Webb R. Report from the VSIA taskforce on standards for reporting optical aberrations of the eye. J Refract Surg 2000;16: S654-5. 35. Chat SW & Edwards MH. Clinical evaluation of the Shin-Nippon SRW5000 autorefractor in children. Ophthalmic Physiol Opt 2001; 21: 87-100. 36. Mallen EA, Wolffsohn JS, Gilmartin B et al. Clinical evaluation of the ShinNippon SRW-5000 autorefractor in adults. Ophthalmic Physiol Opt 2001; 21: 101-107. 37. Jiménez R, Martínez-Almeida L, Salas C et al. Contact lenses vs spectacles in myopes: is there any difference in accommodative and binocular function? Graefe's Arch Clin Exp Ophthalmol 2011; 249: 925-935. 38. Rainey BB, Goss DA, Kidwell M et al. Reliability of the response AC/A ratio determined using nearpoint autorefraction and simultaneous heterophoria measurement. Clin Exp Optom 1998; 81: 185-192. 39. Sokal RR & Rohlf FJ. Biometry: the principles and practice of statistics in biological research, WH Freeman: San Francisco,1969; pp.526-532. 40. Allen PM, Radhakrishnan H & O'Leary DJ. Repeatability and validity of the PowerRefractor and the Nidek AR600-A in an adult population with healthy eyes. Optom Vis Sci 2003; 80: 245-251. 41. Rae SR, Allen PM, Radhakrishnan H et al. Control of SA with soft contact lenses improves high and low contrast visual acuity in young adults. Ophthalmic Physiol Opt 2009; 29: 593-601. 42. Hyman L, Gwiazda J, Hussein M et al. Relationship of age, sex, and ethnicity with myopia progression and axial elongation in the correction of myopia evaluation trial. Arch Ophthalmol 2005; 123: 977–987. 43. Ip JM, Huynh SC, Robaei D et al. Ethnic differences in the impact of parental myopia: findings from a population-based study of 12-year-old Australian children. Invest Ophthalmol Vis Sci 2007; 48: 2520–2528. 44. Jones CM, Atchison DA, Meder R et al. Refractive index distribution and optical properties of the isolated human lens measured using magnetic resonance imaging (MRI). Vision Res 2005; 45: 2352–2366. 45. Yang Z, Lan W, Ge J et al. The effectiveness of progressive addition lenses on the progression of myopia in Chinese children. Ophthalmic Physiol Opt 2009; 29: 41–48. 46. Plainis S, Ginis HS, Pallikaris A. The effect of ocular aberrations on steady-state errors of accommodative response. J Vis. 2005; 5: 466-477. 47. He JC, Burns SA, Marcos S. Monochromatic aberrations in the accommodated human. Vision Res 2000; 40: 41-48. 48. Ninomita S, Fujikado T, Kuroda T et al. Changes of ocular aberration with accommodation. Am J Ophthalmol. 2002; 134: 924-926. 49. Cheng H, Barnett JK, Vilupuru AS et al. A population study on changes in wave aberrations with accommodation. J Vis. 2004; 4: 272-280. 50. Atchison DA, Collins MJ, Wildsoet CF et al. Measurement of monochromatic ocular aberrations of human eyes as a function of accommodation by the Howland aberroscope technique. Vision Res 1995; 35: 313-323. 51. Howland HC & Buettner J. Computing high order wave aberration coefficients from variations of best focus for small articial pupils. Vision Res 1989; 29: 979-983. 52. Lu C, Campbell MCWA, Munger R. Monochromatic aberrations in accommodated eyes. Ophthalmic and Visual Optics Technical Digest 1994; 3:160-163. 53. Artal P, Chen L, Fernandez EJ et al. Neural compensation for the eye’s optical aberrations. J Vis 2004; 4: 281-287. 54. Sawides L, de Gracia P, Dorronsoro C et al. Adapting to blur produced by ocular high-order aberrations. J Vis 2011; 11: 1-11. 55. Siderov J. Improving interactive facility with vision training. Clin Exp Optom 1990; 73: 128-131. 56. Scheiman m, Cotter S, Kulp M et al. Treatment of accommodative dysfunction in children: Results from a randomized clinical trial. Optom Vis Sci 2011; 88: 1343-1352. 57. Charman WN & Radhakrishnan H. Peripheral refraction and the development of refractive error: a review. Ophthalmic Physiol Opt 2010; 30: 321-338. 58. Sankaridurg P, Holden B, Smith III et al. Decrease in rate of myopia progression with a contact lens designed to reduce relative peripheral hyperopia: one-year results. Invest Ophthalmol Vis Sci 2011; 52: 9362–9367.