Download A randomised clinical trial to assess the effect of a dual treatment on

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
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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.