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Myopia progression control lens reverses induced myopia in chicks

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Purpose: To determine whether lens induced myopia in chicks can be reversed or reduced by wearing myopia progression control lenses of the same nominal (central) power but different peripheral designs. Methods: Newly hatched chicks wore -10D Conventional lenses unilaterally for 7 days. The myopic chicks were then randomly divided into three groups: one fitted with Type 1 myopia progression control lenses, the second with Type 2 myopia progression control lenses and the third continued to wear Conventional lenses for seven more days. All lenses had -10D central power, but Type 1 and Type 2 lenses had differing peripheral designs; +2.75D and +1.32D power rise at pupil edge, respectively. Axial length and refractive error were measured on Days 0, 7 and 14. Analyses were performed on the mean differences between treated and untreated eyes. Results: Refractive error and axial length differences between treated and untreated eyes were insignificant on Day 0. On Day 7 treated eyes were longer (T1; 0.44 ± 0.07 mm, T2; 0.27 ± 0.06 mm, C; 0.40 ± 0.06 mm) and more myopic (T1; -9.61 ± 0.52D, T2; -9.57 ± 0.61D, C; -9.50 ± 0.58D) than untreated eyes with no significant differences between treatment groups. On Day 14 myopia was reversed (+2.91 ± 1.08D), reduced (-3.83 ± 0.94D) or insignificantly increased (-11.89 ± 0.79D) in treated eyes of Type 1, Type 2 and Conventional treated chicks respectively. Relative changes in axial lengths (T1; -0.13 ± 0.09 mm, T2; 0.36 ± 0.09 mm, C; 0.56 ± 0.05 mm) were consistent with changes in refraction. Refractive error differences were significant for all group comparisons (p < 0.001). Type 1 length differences were significantly different from Conventional and Type 2 groups (p < 0.001). Conclusions: Myopia progression control lens designs can reverse lens-induced myopia in chicks. The effect is primarily due to axial length changes. Different lens designs produce different effects indicating that lens design is important in modifying refractive error.
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Myopia progression control lens reverses induced
myopia in chicks
Elizabeth L. Irving and Cristina Yakobchuk-Stanger
School of Optometry and Vision Science, University of Waterloo, Waterloo, Canada
Citation information: Irving EL & Yakobchuk-Stanger C. Myopia progression control lens reverses induced myopia in chicks. Ophthalmic Physiol
Opt 2017. https://doi.org/10.1111/opo.12400
Keywords: axial length, chicks,
emmetropization, myopia, myopia progression
control, refractive error
Correspondence: Elizabeth L Irving
E-mail address: elirving@uwaterloo.ca
Received: 1 April 2017; Accepted: 29 June
2017
Abstract
Purpose: To determine whether lens induced myopia in chicks can be reversed or
reduced by wearing myopia progression control lenses of the same nominal (cen-
tral) power but different peripheral designs.
Methods: Newly hatched chicks wore 10D Conventional lenses unilaterally for
7 days. The myopic chicks were then randomly divided into three groups: one fit-
ted with Type 1 myopia progression control lenses, the second with Type 2 myo-
pia progression control lenses and the third continued to wear Conventional
lenses for seven more days. All lenses had 10D central power, but Type 1 and
Type 2 lenses had differing peripheral designs; +2.75D and +1.32D power rise at
pupil edge, respectively. Axial length and refractive error were measured on Days
0, 7 and 14. Analyses were performed on the mean differences between treated
and untreated eyes.
Results: Refractive error and axial length differences between treated and
untreated eyes were insignificant on Day 0. On Day 7 treated eyes were longer
(T1; 0.44 0.07 mm, T2; 0.27 0.06 mm, C; 0.40 0.06 mm) and more
myopic (T1; 9.61 0.52D, T2; 9.57 0.61D, C; 9.50 0.58D) than
untreated eyes with no significant differences between treatment groups. On Day
14 myopia was reversed (+2.91 1.08D), reduced (3.83 0.94D) or insignifi-
cantly increased (11.89 0.79D) in treated eyes of Type 1, Type 2 and Conven-
tional treated chicks respectively. Relative changes in axial lengths (T1;
0.13 0.09 mm, T2; 0.36 0.09 mm, C; 0.56 0.05 mm) were consistent
with changes in refraction. Refractive error differences were significant for all
group comparisons (p<0.001). Type 1 length differences were significantly dif-
ferent from Conventional and Type 2 groups (p<0.001).
Conclusions: Myopia progression control lens designs can reverse lens-induced
myopia in chicks. The effect is primarily due to axial length changes. Different
lens designs produce different effects indicating that lens design is important in
modifying refractive error.
Introduction
The prevalence of myopia has been shown in a number of
studies to be increasing over time
15
and has reached par-
ticularly high proportions in certain Asian populations.
69
This has generated considerable interest in developing
strategies to control myopia. To date these strategies have
involved control of progression or prevention of onset (see
Chassine et al., Cooper et al., Walline, or Sivak for
reviews).
1013
Animal models can provide insight into the
mechanisms controlling eye growth,
14
and as such, they are
valuable tools for developing new strategies for myopia
control and possibly even reversal of existing myopia.
In chicks, minus lenses induce myopia approximately
equal to the inducing lens power.
1517
This myopia comes
about mostly via an increase in axial length
15,17
although, a
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists
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1
Ophthalmic & Physiological Optics ISSN 0275-5408
role for the optical components has also been shown.
1820
These studies clearly demonstrate the ability of the visual
environment to influence ocular growth and refractive
error. Similar findings in other species
2123
including mon-
keys
24
led to the search for myopia control strategies in
humans.
Some success has been achieved in slowing myopic
progression with lens designs that reduce relative periph-
eral hyperopia.
2535
It has not been shown definitively
that it is the reduction in peripheral hyperopia that is
specifically responsible for the success and there is evi-
dence that peripheral refraction is unrelated to myopia
progression in children.
3639
Most of the results attribu-
ted to relative peripheral hyperopia can be explained by
alternative mechanisms.
36
In general, the animal studies,
in chicks, marmosets and guinea pigs, using dual focus
Fresnel
40,41
or two zone lenses
4244
that claim to support
the peripheral hyperopia hypothesis give results that are
consistent with a response close to the average or
weighted average power across the pupil. As such, none
of these studies have findings that completely inhibit
lens-induced myopia. Two studies have reported results
that do not correspond to the average power of the lens
across the pupil. In one, monkeys subjected to dual focus
lenses emmetropise to the relatively myopic focus.
45
In
the other, we (Woods et al.
46
) showed that lens induced
myopia can be completely inhibited in chicks when the
minus power is combined with Visioneering Technologies
Inc. (http://www.vtivision.com) myopia progression con-
trol extended depth of focus lens designs (US patents
6,474,814/7,178,918). These lenses have a relatively posi-
tive powered peripheral lens design.
There are at least two possible explanations for the
Woods et al.
46
results. The first is that a reduction in rela-
tive peripheral hyperopia does play an active role in reduc-
ing the development of myopia. Alternatively, a second
explanation is that the increased depth of focus of the
lenses reduces the emmetropization signal and the chicks
simply fail to emmetropise to the inducing lens power.
Should the second explanation hold, then if one were to
induce myopia and subsequently apply the myopia progres-
sion control lenses, the expectation would be that the
chicks would remain myopic (i.e., there is no need for the
refractive error to change and no signal for change). If how-
ever, the chicks were to decrease in myopia, then there
would be strong evidence that the eyes were in fact
responding to the periphery of the lens. Therefore, the
specific aim of this study was to determine whether myopia
induced with conventional minus lenses worn for a period
of 7 days could be reversed or reduced by wearing these
myopia progression control lenses of the same nominal
power but different peripheral designs (Type 1 and Type
2), over the next 7 days.
Methods
The study received ethical approval from the University of
Waterloo’s Animal Care Committee, complied with the
Canadian Council on Animal Care use and treatment of
research animals, and adhered to the ARVO guidelines for
the use of animals in ophthalmic and vision research. The
animals used in the study were Ross-Ross strain chickens
(Gallus gallus domesticus). They were raised on a 14 h light/
10 h dark cycle in stainless steel brooders at 32°C and given
food and water ad libitum. Chicks were monitored twice
daily, once by the animal care technicians for health, and
once by the researcher to assess the lenses.
All lenses were supplied by Visioneering Technologies
Inc. and had a measured power of 10.00D, verified using
a lensometer (focimeter) with a 5 mm aperture. Conven-
tional and Test lenses were identical in every respect, with
the exception that the peripheral power profiles of the Test
lenses had a continuous relative positive power gradient
without any distinct optical zones or discontinuities. For
specific details regarding the power profile the reader is
referred to Figure 3 and the formula in Claim 1 of US
patent #6474814. Type 1 decreased in minus from 10.00D
at the centre to 7.25D (i.e., 2.75D less minus) at the pupil
edge based on a 2.5 mm pupil diameter and were designed
for and fitted at a vertex distance of 5 mm. Root mean
square higher order aberrations provided by Visioneering
Technologies, Inc. for a 10.00D lens power at a 2.5 mm
aperture were 0.041 microns, as measured by the NIMO
Model TR1504 (Lambda-X, http://www.lambda-x.com)
using a phase-shifting Schlieren measurement technique.
Type 2 lenses were similar but with a less steep power gra-
dient which decreased from a central power of 10.00D to
8.68D (i.e., 1.32D less minus). Aberration data were not
available for the Type 2 lenses but would be expected to be
less than that of the Type 1 lenses. The overall diameter of
the lenses was 20 mm including a flat flange to which Vel-
cro
TM
was glued that was used to attach the lens to the bird.
The optical portion of the lens was 15 mm in diameter and
the lens was transparent throughout. The lens designs,
which are highly aspheric and gradually change power cre-
ating a smooth, continuous power curve of increasing rela-
tive plus, were originally created based on human
physiology and the predicted amount of lens power
required to create the unique extended depth of focus.
Those power profiles were then scaled to the anatomy (i.e.,
the pupil) of the chick to be equivalent to what the relative
power profile would be in a human. Two different lens
designs were chosen to be quite distinct from each other, so
that the possibility of a dose-response relationship could be
examined between the two different lens designs.
Fifty-two newly hatched chicks were fitted unilaterally
with Conventional design 10.00D lenses (spherical
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists2
Reversal of induced myopia in chicks E L Irving and C Yakobchuk-Stanger
design), which they wore for 7 days to induce myopia. The
lenses were attached to the right eye (RE) of all birds using
Velcro
TM
rings held on by cyanoacrylic glue to the feathers
around the eye. This allowed the lenses to be removed for
cleaning. Two birds lost lenses prior to Day 7 and were
eliminated from the study. On Day 7, the remaining 50
myopic chicks were randomly divided into three groups.
Sixteen chicks were fitted with Type 1 lenses, 19 chicks were
fitted with Type 2 lenses, and 15 remained with Conven-
tional design lenses. Thus, all right eyes are considered trea-
ted; initially all had Conventional designs and then right
eyes were subsequently treated with either Conventional,
Type 1 or Type 2 designs. The left eyes were untreated and
served as control eyes.
Refractive error and axial length (anterior cornea to
retina) were measured on alert birds using retinoscopy
(precision of 0.50 dioptres)
5,47
and ultrasonography (Accu-
tome A-Scan Plus Ultrasound, http://www.accutome.com,
precision of 0.02 mm)
48
respectively on Days 0 (prior to
lens application), 7 and 14 on all birds. The experimenter
making the refractive error and axial length measurements
was blind as to which of the three groups the chicks
belonged. Lenses were only removed for measurement and
cleaning when necessary. Birds that lost their lenses were
removed from the study (N=9; 2 prior to day 7, 1 Con-
ventional, 2 Type 1, 4 Type 2). For birds with astigmatic
refractive error, the mean ocular refractions (spherical
equivalent) were used in the analysis. Results were analysed
with respect to the mean differences (Mean [right eye (RE)
left eye (LE)] S.E.) between treated and untreated eyes
in order to control for the small eye artefact.
49
Compar-
isons were made between treatment assessment day (within
groupDay 0, Day 7, Day 14) and lens design (between
groupsConventional, Type 1, Type 2) using a mixed
design ANOVA and Bonferonni corrected post-hoc tests
(Statistica 8 software, http://www.statsoft.com).
Results
On Day 0 there were no statistically significant differences
(p<0.05) in refractive error or axial length between trea-
ted (RE) and untreated (LE) eyes for any of the groups and
therefore no interocular differences between groups (see
Table 1,Figure 1). On Day 7 treated eyes were longer and
more myopic (~10D 95% compensation) than untreated
eyes for all groups and there were no statistically significant
differences (p<0.05) between the groups (Table 1,
Figure 1).
At Day 14, 14 Conventional treated birds, 14 Type 1 trea-
ted birds and 15 Type 2 treated birds still had lenses. As
shown in Table 1 and Figure 1, treated eyes of chicks wear-
ing Conventional design lenses were still longer (Mean RE-
LE =0.56 mm 0.05) and more myopic (Mean RE-
LE =11.89 D 0.79) than untreated eyes. Myopia pro-
gression control Type 1 treated eyes became more hyper-
opic (Mean RE-LE =2.91 D 1.08) and were shorter
(Mean RE-LE =0.13 mm 0.09) than untreated eyes.
Figure 1d,e indicates that treated eyes were longer than
untreated eyes at Day 7. Treated eyes wearing myopia pro-
gression control Type 1 lenses that were longer than their
untreated counter parts on Day 7 (8.97 treated vs 8.53
untreated) did become shorter than their untreated coun-
terparts at Day 14 (9.47 treated vs 9.60 untreated), but did
not shrink (9.47 Day 14 vs 8.97 Day 7). Rather, they contin-
ued to grow over the 7-day period, albeit at a slower rate
than previously (0.07 mm/day week 2 treatment vs
0.17 mm/day week 1 treatment). In Type 1 treated birds
the treated eyes also grew slower during week 2 of
treatment (0.07 mm/day) than the untreated eyes
(0.15 mm/day). Refractive error, on the other hand, did
reverse direction in absolute (Figure 1a) as well as relative
(Figure 1c) terms with the Type 1 lenses. Myopia progres-
sion control Type 2 treated eyes were more myopic (Mean
Table 1. Mean (S.E.) for treated eyes (RE), untreated eyes (LE), and differences (RE-LE) in refractive error (Rx) in Dioptres (D) and axial length for Days
0, 7 and 14 for Conventional, Type 1 and Type 2 Treated Birds that still had their lenses at Day 14
Day
Rx RE
D (S.E.)
Rx LE
D (S.E.)
Rx RE-LE
D (S.E.)
Length RE
mm (S.E.)
Length LE
mm (S.E.)
Length RE-LE
mm (S.E.)
Conventional lens (n=14)
0 3.93 (0.63) 3.93 (0.64) 0.00 (0.14) 7.90 (0.06) 7.84 (0.06) 0.05 (0.05)
76.07 (0.62) 3.43 (0.25) 9.50 (0.58) 9.04 (0.04) 8.64 (0.07) 0.40 (0.06)
14 9.36 (0.71) 2.54 (0.19) 11.89 (0.79) 10.31 (0.06) 9.75 (0.08) 0.56 (0.05)
Type 1 lens (n=14)
0 3.86 (0.77) 3.86 (0.70) 0.00 (0.16) 7.80 (0.07) 7.81 (0.04) 0.01 (0.05)
75.96 (0.55) 3.64 (0.25) 9.61 (0.52) 8.97 (0.10) 8.53 (0.07) 0.44 (0.07)
14 5.27 (1.12) 2.36 (0.18) 2.91 (1.08) 9.47 (0.11) 9.60 (0.08) 0.13 (0.09)
Type 2 lens (n=15)
0 4.37 (0.68) 4.37 (0.67) 0.00 (0.05) 7.72 (0.05) 7.77 (0.04) 0.05 (0.06)
75.57 (0.58) 4.00 (0.24) 9.57 (0.61) 8.88 (0.05) 8.61 (0.06) 0.27 (0.06)
14 1.47 (0.88) 2.37 (0.12) 3.83 (0.94) 10.02 (0.09) 9.66 (0.05) 0.36 (0.09)
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists 3
E L Irving and C Yakobchuk-Stanger Reversal of induced myopia in chicks
RE-LE =3.83 D 0.94) and longer (Mean RE-
LE =0.36 mm 0.09) than untreated eyes but less
myopic than Conventional treated eyes. Some but not all
treated eyes developed astigmatism by day 14 (Table 2).
No birds had astigmatism >1D on Day 0 or 7. The
prevalence of astigmatism >1D on Day 14 for Conven-
tional, Type 1 and Type 2 treated eyes was 14%, 43%
and 53% respectively. Using Fisher’s exact test, this
prevalence was not significantly different between Con-
ventional and Type 1 (p=0.21) or Conventional and
Type 2 (p=0.0502) treated eyes.
A mixed design analysis of variance indicated a signifi-
cant effect of lens design for both refractive error difference
(F
2,40
=33.7; p<0.001) and axial length difference
(F
2,40
=7.1; p=0.002). There was also a significant main
effect of day for both refractive error difference
(F
2,80
=193.6; p<0.001) and axial length difference
(F
2,80
=30.6; p<0.001) as well as a significant interaction
between lens type and day for refractive error difference
(F
2,80
=50.8; p<0.001) and axial length difference
(F
2,80
=12.6; p<0.001). Post hoc tests showed that the
refractive error differences for all of the groups on Day 14
Figure 1. Mean (S.E.) change in refractive error and axial length for three treatment days, for Conventional, Type 1, and Type 2 lens designs. Panels
(a, d) treated eye, (b, e) untreated eye, (c, f) difference between treated (RE) and untreated (LE) eyes (*p<0.001).
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists4
Reversal of induced myopia in chicks E L Irving and C Yakobchuk-Stanger
were significantly different from each other (p<0.001).
On Day 14 Type 1 length differences were significantly dif-
ferent from both the Conventional group and the Type 2
group (p<0.001). Type 2 length differences were not sig-
nificantly different from the Conventional group
(p>0.05).
Figure 2 shows the individual variability of refractive
error difference between the two eyes and axial length dif-
ference between the two eyes for the treatment days
assessed and the three lens designs. Figure 3 shows the cor-
relation between refractive error and axial length differ-
ences between the two eyes on Day 14 (Pearson’s
correlation coefficient, r=0.64, p<0.05).
Discussion and conclusions
Although unexpected, it is clear from these results that
these myopia progression control lens designs can
reverse lens-induced myopia in 714 day old chickens
and that the effect is largely the result of axial length
changes (Figure 3). The results also suggest that periph-
eral lens design can affect refractive error. If in the
Woods et al.
46
study the large depth of focus produced
by these lenses simply overwhelmed the normal
emmetropization mechanism such that the eyes did not
respond to the central minus power, then the expecta-
tion in this experiment would be that the birds would
again not respond and remain myopic once myopia had
been induced by the Conventional lenses. Since the birds
did not maintain the same degree of myopia (and in
the case of the Type 1 design, had a complete refractive
reversal) that hypothesis is not supported. The two dif-
ferent myopia progression control lens designs behaved
differently, indicating that the lens design itself is an
important factor.
There appear to be some outliers in the data. For exam-
ple, three birds (one from each group) did not become as
myopic on Day 7 with the Conventional lenses as one
would expect (Figure 2). It is not clear why this occurred as
there were no obvious differences between these birds and
those that did respond as expected. There were also some
birds (four on Day 7 and one on Day 14) whose refractive
errors were not consistent with their axial lengths. Again,
the reason for this is unclear. Axial length measurement
error, inherent in measuring very small eyes, may account
for some of the differences, however other physiological
factors, such as cornea and crystalline lens powers, may
contribute.
Table 2. Astigmatism (Dioptres, D) in treated eyes (RE) for Conventional,
Type 1 and Type 2 Treated Birds that still had their lenses at Day 14
Percentage with
astigmatism Mean (S.E.) D
Conventional lens (n=14) 14% 1.357 (0.923)
Type 1 lens (n=14) 43% 2.679 (0.913)
Type 2 lens (n=15) 53% 3.133 (0.844)
Figure 2. Variability of axial length difference and refractive error dif-
ference between the two eyes for individual birds on the three treat-
ment days, for three lens designs (a) Conventional, (b) Type 1 and (c)
Type 2.
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists 5
E L Irving and C Yakobchuk-Stanger Reversal of induced myopia in chicks
While every effort was made to keep the lenses clean and
centred on the pupil, the effects of any inadvertent decen-
tration are unknown. Chickens, like most birds, have lim-
ited eye movement.
50,51
They also do not have a fovea,
although they do have an area centralis. Any effects of eye
movement and/or looking through the periphery of the
lens with ‘central’ vision as a result of eye movement could
not be controlled for and are unknown. That being said, no
behavioural differences between birds with regard to head
or eye posture were observed and birds with Test lenses
could not be distinguished from those with conventional
lenses on this basis. It is highly unlikely that any birds
viewed only through the peripheral portion and not the
central portion of the lens.
It is well known that experimental myopia reverses quite
rapidly in chicks (4 days) when either form deprivation
52
or an inducing lens
17,53,54
is removed. Induced myopia also
reverses when negative lenses are replaced with positive
lenses,
15,40
although in chicks this can induce significant
astigmatism.
15
The question addressed by the current
experiment is whether or not myopia can be reversed while
maintaining the same minus power in the central portion
of the lens and altering the peripheral power. To our
knowledge, the results from the Type 1 lens are the first in
which myopia is completely reversed while maintaining the
same central minus power and no positive power within
the lens.
Schaeffel and Howland
55
did have a portion of their
birds recover from myopia despite continuing to wear
minus lenses. Unlike their findings, none of our birds that
were treated continuously with the conventional lenses
showed recovery. McFadden et al.
40
have shown partial
reversal of previously induced myopia in guinea pigs using
5D/+5D Fresnel lenses. Their lens design had both posi-
tive and negative power presented within the pupil. The
refractive result for replacement of the initial myopia
inducing minus lens with Fresnel lenses (5D/+5D) was
intermediate, between that of continued single vision
minus lens wear and replacement of the initial myopia
inducing lens with a single vision positive lens. Liu and
Wildsoet
43
induced myopia in 12 day old chicks by having
them wear single vision 10D lenses for 5 days. They then
replaced the 10D inducing lenses with 2 zone lenses
(5C/10P or 10C/5P). There was some regression of
the previously induced myopia as would be expected from
averaging of the power of the 2 zones but all chicks still
remained somewhat myopic. Tse et al.
41
did get complete
recovery when 10D was replaced with a lens design incor-
porating both +and 10D. This also is the response that
would be expected if the eye were responding to the average
of the two powers within the lens, which in the Tse et al.
study would have averaged to plano.
Although the Visioneering Technologies Inc. myopia
progression control lenses have a gradient rise in relative
plus power, the actual power throughout the lens is still
negative. This negative lens power was verified by the use
of a lensometer with a 5 mm lens stop aperture. Unlike the
McFadden et al.
40
experiment, our chicks cannot be
responding directly to plus power as there is no actual plus
power within the lens design. However, this does not pre-
vent the peripheral image from lying in front of the retina.
If the central power corrects the myopia induced by the
Conventional lenses and the eye shape is flatter than the
image surface created by the nominal central lens power,
which in the chick it will be, any reduced minus power in
the periphery will put the image in front of the retina pre-
sumably sending a stop signal to axial eye growth. This of
course will change as the eye changes shape and the exact
image position will depend where the peripheral focus was
to start with, the shape of the eye and the manner in which
the eye shape changes.
Similar to our study, the Liu and Wildsoet
43
experiment
does have negative power throughout the lens (their 10C/
5P lens would be most similar to ours), but unlike our
study, they did not observe complete reversal of previously
induced myopia. This finding would suggest that the gradi-
ent nature of the design of the Visioneering Technologies
Inc. myopia progression control lenses is of some signifi-
cance, with a potential dose-response type relationship
being shown with these data between the Type 1 and Type
2 myopia progression control lens designs.
A significant difference between our study and previous
ones is that we used a lens design with continuous power
change rather than one with discrete zones. It has been
shown that the size of the central zone has an effect on
whether or not central refractive status is affected.
54,5658
It
may be that the absolute power values are not as important
as the relative difference between the centre and the
Figure 3. Correlation between axial length difference between the
two eyes and refractive error difference between the two eyes for Day
14 birds (r=0.64, p<0.05).
©2017 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists6
Reversal of induced myopia in chicks E L Irving and C Yakobchuk-Stanger
periphery or possibly the change in power from centre to
periphery. These data do suggest that perhaps the exact
mechanism is more complicated than simply responding to
absolute image position; there could be integration of
information such that the eye is detecting the defocus gra-
dient itself and using this to control eye growth.
Another possibility is that the lenses are creating a ‘vir-
tual aperture effect’ with the Type 1 lenses creating a smal-
ler ‘aperture’ and therefore greater effect than the Type 2
lenses. Peripheral annular blur is visible through Type 1 but
not Type 2 lenses. We have seen in other animal studies
with real apertures that once the aperture size decreases
below a critical level, usually about 4 mm the normal
response to imposed defocus is altered.
44,54,5660
This has
been interpreted as the periphery having more influence
than the centre as the aperture decreases. Irving et al.
54
found decreased compensation to both plus and minus
lenses with apertures 5 mm. Interestingly in these experi-
ments, despite the periphery being a translucent goggle, the
default did not appear to be form deprivation myopia as
would be expected if the periphery was simply having more
influence. There may be some similarities to the ‘set point’
of McLean and Wallman
59
or the ‘eye size effect’ of Sieg-
wart and Norton.
61
McLean and Wallman, creating large
amounts of blur with high powered cylindrical lenses,
observed that the eye returned to some ‘set point’. Siegwart
and Norton found that pre-treatment with plus lenses
resulted in increased response to subsequent treatment and
gave this as evidence for the operation of an ‘eye size’
mechanism. It is possible that the peripheral optics of these
lenses are preventing the centre from controlling eye
growth without providing any usable peripheral signal and
the eye is reverting to some inherent refractive state or ‘set
point’ via some ‘eye size’ mechanism. Further study is nec-
essary to understand the underlying mechanisms of refrac-
tive control in general and the current lens design in
particular. These results provide incentive to explore new
possibilities.
A limitation of the study is that peripheral refractions
and ocular component data other than axial length were
not obtained. Axial length measures were to the retina so,
although we do not know what choroidal effects there may
have been, any choroidal effects on axial length would have
been accounted for in the length measures. Peripheral
refractions and ocular component measures would be nec-
essary for future research in optical modelling of image sur-
faces in relation to three dimensional continuous growth,
but getting accurate, reliable peripheral refraction data will
be a challenge because of the small eyes and inability to
control fixation in chickens. Any induced astigmatism
should also be considered.
Apart from furthering our knowledge of how these myo-
pia progression control lenses might work, the results of
this study raise the issue of whether or not myopia, once it
exists, can be reversed as the eye grows. Up until now
efforts have been directed at reducing progression, or at
best, preventing its occurrence. If in fact active myopia
reversal turns out to be achievable, the practical application
would be of considerable consequence to the human condi-
tion.
Acknowledgements
As well as providing financial support for the study, the
lenses were designed and provided by Visioneering Tech-
nologies, Alpharetta GA, (US patents 6,474,814/7,178,918).
Funding support to E. L. Irving from Natural Sciences and
Engineering Research Council of Canada (NSERC) Discov-
ery Grant 06554. These data have been partially presented
at the American Academy of Optometry Annual meeting,
November 12, 2014, Denver, Colorado, USA. The authors
wish to acknowledge the editorial contributions of Sally
Dillehay, OD and Linda Lillakas to this work.
Disclosure
The authors have no proprietary interest in any of the
materials mentioned in this article. Visioneering Technolo-
gies, Inc. partially funded the study and paid consulting fees
indirectly related to the study to E. Irving.
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E L Irving and C Yakobchuk-Stanger Reversal of induced myopia in chicks
... The dose-dependent effect of optical interventions in minimizing lens-induced myopia in animal studies was attributed mainly to lens design features such as the amount and area of lens addition, 19,20 peripheral defocus, and lens asphericity. 21,22 This dose-dependent relation-ship was also found in human clinical studies for ophthalmic lenses with higher addition 10,12 and contact lenses with higher asphericity. 23 Compared with SVL, during the second year, HAL remained effective in slowing myopia progression. ...
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... 30 The lens design has been shown in animal (chick) studies both to inhibit the progression of up to 210.00 D of myopia 31 and to reverse it completely once myopia has developed. 32 In children, the lens design has been shown to move both meridians of the retinal image inside the retina. 33,34 In addition, the lens design has been shown to reduce the lag of accommodation and improve measured accommodative amplitudes in children, as compared to a single-vision contact lens. ...
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To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Variation in age-specific myopia prevalence for differing years of birth and educational level. There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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Myopia has increased worldwide during recent years and is becoming a serious public health problem. In East Asia, the prevalence can reach 80% of the population. The focus for screening and interventions should be on early life during childhood when myopia progression is faster. Review and discussion of the recent literature on potential interventions for preventing the development of myopia or slowing its progression. Increased time spent outdoors is a protective factor for myopia progression. Undercorrection increased myopia progression and optimal correction is mandatory. The use of progressive or bifocal lenses (spectacles or contact lenses) may yield a slowing of myopia by limiting eye accommodation. Rigid gas permeable contact lenses were found to have few effects on myopic eye growth. A marked slowing of myopia was observed with orthokeratology by temporarily changing the curvature radius of the cornea. The largest positive effects for slowing myopia progression were observed with atropine eyedrops with an interesting dose effect. The benefit of surgical scleral reinforcement is reserved for severe and progressive myopia. In this review, we discuss optical and pharmacologic interventions that can be used in myopia management.
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PURPOSE. To determine whether the use of progressive addition spectacle lenses reduced the progression of myopia, over a 2-year period, in Hong Kong children between the ages of 7 and 10.5 years. METHODS. A clinical trial was carried out to compare the progression in myopia in a treatment group of 138 (121 retained) subjects wearing progressive lenses (PAL; add + 1.50 D) and in a control group of 160 (133 retained) subjects wearing single vision lenses (SV). The research design was masked with random allocation to groups. Primary measurements outcomes were spherical equivalent refractive error and axial length (both measured using a cycloplegic agent). RESULTS. There were no statistically significant differences between the PAL and the SV groups for of any of the baseline outcome measures. After 2 years there had been statistically significant increases in myopia and axial length in both groups; however, there was no difference in the increases that occurred between the two groups. CONCLUSIONS. The research design used resulted in matched treatment and control groups. There was no evidence that progression of myopia was retarded by wearing progressive addition lenses, either in terms of refractive error or axial length.
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Slowing the progression of myopia has become a considerable concern for parents of myopic children. At the same time, clinical science is rapidly advancing the knowledge about methods to slow myopia progression. This article reviews the peer-reviewed literature regarding several modalities attempting to control myopia progression. Several strategies have been shown to be ineffective for myopia control, including undercorrection of myopic refractive error, alignment fit gas-permeable contact lenses, outdoor time, and bifocal of multifocal spectacles. However, a recent randomized clinical trial fitted progressing myopic children with executive bifocals for 3 years and found a 39% slowing of myopia progression for bifocal-only spectacles and 50% treatment effect for bifocal spectacles with base-in prism, although there was not a significant difference in progression between the bifocal-only and bifocal plus prism groups. Interestingly, outdoor time has shown to be effective for reducing the onset of myopia but not for slowing the progression of myopic refractive error. More effective methods of myopia control include orthokeratology, soft bifocal contact lenses, and antimuscarinic agents. Orthokeratology and soft bifocal contact lenses are both thought to provide myopic blur to the retina, which acts as a putative cue to slow myopic eye growth. Each of these myopia control methods provides, on average, slightly less than 50% slowing of myopia progression. All studies have shown clinically meaningful slowing of myopia progression, including several randomized clinical trials. The most investigated antimuscarinic agents include pirenzepine and atropine. Pirenzepine slows myopia progression by approximately 40%, but it is not commercially available in the United States. Atropine provides the best myopia control, but the cycloplegic and mydriatic side effects render it a rarely prescribed myopia control agent in the United States. However, low-concentration atropine has been shown to provide effective myopia control with far fewer side effects than 1.0% atropine. Finally, two agents, low-concentration atropine and outdoor time have been shown to reduce the likelihood of myopia onset. Over the past few years, much has been learned about how to slow the progression of nearsightedness in children, but we still have a lot to learn.
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To estimate the age-specific prevalence of myopia in Asia. We searched PubMed, Embase, and Web of Science from their inception through September 2013 for population-based surveys reporting the prevalence of myopia in adults or children in Asia. We pooled the prevalence estimates for myopia by age groups and by year of birth using a random-effects model. We identified 50 eligible population-based studies including 215,672 subjects aged 0 to 96 years reporting the prevalence of myopia from 16 Asian countries or regions. Myopia was found to be most prevalent (96.5%; 95% confidence interval, 96.3 to 96.8) in Koreans aged 19 years. There was no significant linear age group effect on the prevalence of myopia in the whole Asian population but there was a U-shaped relationship between both age and year of birth and the prevalence of myopia. The prevalence of myopia was also higher in those older than 70 years (36.3%; 95% confidence interval, 27.6 to 45.0) compared with other age groups, which revealed nuclear cataract-myopia shifts in refraction. There is a large variation in the age-specific prevalence of myopia in Asia. A U-shaped relationship between age and the prevalence of myopia was found in the whole Asian population. The analysis is essential to guide future eye health care, intervention, and clinical management in Asia.