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After 10 years of research in chicks and monkeys inducing myopia by
suturing the lids, they knew that the mechanism for controlling eye
growth was local to the retina, because it worked the same after cutting
the optic nerve. They also knew that atropine could block this “form
deprivation myopia” in chicks and monkey eyes.
Then in 1988 Frank Schaffel (photo), from Germany, became involved
showing that negative and postive lenses could be compensated by
regulated eye growth in few days. Eyes grow longer with negative
lenses and shorter with positive lenses. And the mechanism is
reversible because when the lens wear is interrupted the eye returns to
its normal refraction.
Here we see a picture of wonderful review published by Josh Wallman
before he passed by, which shows how the choroid becomes thinner
with negative lenses and the eye elongates faster, while the choroid
thickens before the eye grows slowlier with positive lenses.
If the negative lens is removed after one week in chicks the choroid
becomes thicker and the eye elongation becomes slower such that the
myopia is compensated in few days. This can happen in a period of few
weeks after birth in chicks and in some months in monkey eyes. As the
animals become older the mechanism is slower. From these
experiments it became clear the the image plane at the retina was
governing the rate of axial elongation. It is also clear from these
experiments with negative lenses that increase ocular growth that
children should never be over refracted with negative lenses, because
this may increase their rate of progression. Undercorrection is also not
an option, because some studies have also shown greater progression.
This mechanism seems to be universal as has been reproduced in
birds, fish and many mammals.
Here the image of a fish growing with imposed negative lenses.
By 2010 cientists in myopia área were studýing the formation or images
in the eye wearing spectacles. Then Charman reviewed this issue and
he postulated that the peripheral hyperopic defocus in corrected myopic
eyes could induce further ocular growth, as it was well known that
images at the back of the retina increase ocular growth.

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Trying to put part of the image plane in front of the retina, these
researchers published the effect of peripheral add plus in contact lenses
for myopic children. The concentric ringes have alternatively far and
near add corrections. Wiith these type of contact lenses the axial
elongation and myopia progression was reduced by 50% in a period of
18 months. There are now many patents and experiments with similar
peripheral plus add contact lenses and spectacles. Some are already
commercially available in Asia and Spain, but there is not much
research on their effectiveness.

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This is the fluorescence image of an orthokeratology contact lens in
place. You can see the flat center and a peripheral ring where the cental
epithelium is pushed centrifugally to flatten the cental part of the cornea.
This randomized study confirmed what more than ten case series or
pilot studies were showing. Orthokeratology decreases myopia
progression and axial growth in myopic children. This has been recently
reviewed in a meta-analysis in Jun-Kang Si, et al.,
Optom Vis Sci, 2015.
This is the topography of an orthokeratology treated eye. You can see
the central applanated section for clear distance vision at the fovea.
There in red there is a ring of greater corneal power produced by the
displaced epithelium. With this multifocal cornea, images of rays
passing by this anular ring fall in front of the retina at the mid periphery.
There is no doubt that these eyes have increased spherical aberration.
But if part of the image plane is put in front of the retina, especially at
the periphery, then one can understand why orthokeratology decreases
axial elongation and myopia development. Jaime Paune developed a
contact lens based on the topography of the orthokeratology, and is
selling this lens in Spain.
Here we can see the results of these lenses in a small prospective
study. (AL is axial length).
Cooper Vision has designed a contact lens for presbyopia with center
for distance called Proclear that has been shown (ten years ago) to
arrest myopia progression in a small clinical trial. Based on the Anstice
and Phillips lens they have designed and tested in a clinical trial the
MiSight contact lens with about 60% reduction in myopia progression.
This lens is now available in most countries.
It is yet not clear if the plus add produces myopic defocus (during
distance and near vision) in the central fovea or in the whole macular
region at the posterior pole. Both could be true.
On the other hand, following a similar principle of peripheral plus add,
Carly Lam and his team, designed spectacles with peripheral small
spots of plus add. These DIMS spectacles have been tested in a clinical
trial with similarly good results as previously described contact lenses.
These spectacles for myopia control are available in Asia.
Here you can see the difference in change in myopia between controls
and DIMS spectacle users.
The Brien Holden Vision Institute has produced also an EDOF
(Extended Depth of Focus) contact lens for myopia control called
MYLO.
Thomas Aller, in Visioneering Technologies, Inc. has tested and
developed another EDOF contact lens for myopia control.
If we are about to prescribe a treatment for arresting myopia
progression in a given child we should evaluate risk factors. Family
history was usually taken as genetic, but it includes also environmental
factors, like reading habits that can be learned from parents. The family
history of high myopia has relevance in the sense that high myopic
parents know well the burden this poses for their children in the future,
and are thus more prone to accept a treatment. Besides, when one
family member has high myopia of early onset, 25 to 50% of the
offspring may have genetic high myopia. The other risk factors are
treated in the next slides.
This is what we studied.

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Here we presented the first study of refractive errors in adults of
Argentina.

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These are the myopes of our unselected sample of Argentinean office-
workers with an average of 6 years of University study and a
prevalence of myopia of 29%. Myopes know accurately at what age
they began to use lenses (in the x axis of the graph). In the y axis, the
amount of myopia in adulthood shows that early onset is related to
greater amounts of spherical equivalent in adult life. In this sample, half
of myopic cases are developed after age 20, being then adult onset
50% of the prevalence.

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In Asia, Europe and Usa there have been increments in the prevalence
of myopia in recent years.

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Tscherning in Denmark showed in the early years of Ophthalmology
that myopia was related to occupation. From this early study until the
time of Sorsby, myopia was thought to be due to enviornmental factors,
and Ophtalmolgist recommende hygenic treatments for myopic children,
like staying more outdoors and not reading. After Sorsby’s studies, by
the mid of the XX century, these ideas were abandoned because of a
genetic theory of myopia.

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This change in prevalence in a short period cannot be due to genetic
factors. Enviroment has changed in East Asian Cities like Guangzhou,
Korea, Taiwan, Singapore and Beijing.

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An early study in Jewish orthdox males with high prevalence of myopia
and high myopia atributted this fact to reading habits. But other
environmental factors could be playing a role as we will see later.

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Here you have the refractive error distribution of those Jewish children,
showing the myopic shift with a mean of –4 diopters compared to a
normal distribution in children from general schools or orthodox
females..Orthodox males have nearly 20% prevalence of high myopia
over -6 diopters.

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In Korea, 15 years later we have the same picture as in orthodox males.
The majority of the population is myopia around a mean of -4 diopters,
and 20% are high myopic,
Authorities in these countries are greatly concerned about the public
health impact this prevalence may have when these subjects get older
and have maculopathy.

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Here you can intuitively see the high prevalence of myopia in Korea.

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This shows how low is the prevalence of myopia in Villa Maria
(Argentina) where children spend 4 hours a day outdoors.

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At ARVO 2007 we presented a study showing how different was myopic
refractive error distribution among between myopes who had completed
more or less than 7 years of university study. Today further research
has stablished clearly the association between near work and myopia
progression
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At ARVO 2006 this association was first mentioned by the Australian
group involved in the Sydney Myopia Study.
He is Ian Morgan, biologist and epidemiologist involved in the Sydney
Myopia Study, who has actively promoted that myopia epidemic in east
Asia is enviromenmentally driven.
They saw that chinese Singaporean children moving to Sydney
(Australia) had much lower prevalence of myopia, and the main
difference between both chinese groups from the same ethnic origin
was the greater amount of time they spent outdoors in Sydney.

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The Sydney Myopia Study evaluated myopia incidence along 6 years
time and measured nearwork and outdoor exposure. Then, as seen in
the graph, the relative risk to develop myopia increases with both risk
factors but is greater for low outdoor exposure.
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A three years follow up in a randomized control study showed that
children in schools having only two 20min long obligatory periods of
outdoor exposure had lower incidence of myopia. Progression was also
less in children with higher outdoor exposure (0.86 diopters vs. 0.75
diopters).
At ARVO 2015 this group from Guangzhou presented a glass
classroom where children are already studying to see if incidence and
progression of myopia slows down with this approach.
Same classrooms
This shows how the tendency of increasing visual impairment by
myopia decreases after 2010 when the Program Tian Tian 120 in all
schools of Taiwan took children for 2 horus a day outdoors in schools all
over the country..

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This was a randomized controlled double blind study using 1% atropine
drops daily in myopic children in Singapore, and it showed clearly that
the control group (in red) had a mean progression of 1 diopter in two
years. On the other hand, the treated eyes (in yellow) had stayed stable
in 65% of cases, with less than 0.50 diopters progression in two years.
Yet, 15% of the placebo group had also been stable, thus showing that
atropine can slow myopic progression, on the one hand, but also that
some naturally occurring myopia is stable without any treatment.

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Here we see the refractive change in each group before, during and
after the two year treatment period. After the treatment ended and the
drop was stopped, the treated group had an increased rate of myopic
change during the following 6 months. Then the rate of myopic change
became the same as that of the control group. This treatment is not well
tollerated because of photophobia and accomodative parallisis.
***NOTE: These data are very similar to the ones published by H.
Gimbel (1977) for treated vs untreated individuals

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In recent years atropine drops at 0.05%, 0.025%, and 0.01% have been
compared with placebo over a 1-year period in a randomized, placebo-
controlled, double-masked trial witha total of 438 children aged 4 to 12
years with myopia. This last study suggests that for small rapidly
progressing children in Hong Kong the best dilution could be 0.05%
atropine drops.
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This poster presented at ARVO 2016 shows that in young adults the
message from the retina is acting at the choroid. Subjects wore
negative lenses during one hour and choroidal thickness was measured
with OCT. They found that hyperopic blur thinned the choroid, and that
this effect was reversed by atropine drops. Thus atropine may be acting
at retinal or choroidal sites.

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This very recent paper shows the influence of blue ligth in arresting
myopia progression

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Here you can see opposite changes in axial elongation with Red or
Green vs. Blue light.

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And this is a new paper showing that spectacles that allow violet light to
pass into the eye arrest myopia progression

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This is the pattern of ligth blockade of such spectacles

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And this is the difference in myopia progression with the
spectacles….not much but it is only a filter in the spectacles.

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To complicate more the link between reading and myopia, recent
experiments by Aleman & Schaeffel in Germany studied with high
resolution OCT the choroids of human volunteers reading white or black
letters under opposite backgrounds, and these subjects developed
changes in the chorod similar to those produced by wearing plus or
minus lenses or different colours in the light. That is ON contrast of
white letters under dark background increase choroidal thickness
similarly to when ocular elongation is slower. So the link between axial
elongation and myopia development in schoolyears when children begin
to read could be the fact that they read black text under white
background. We are still lacking proof that myopia can be arrested
reading with inverted contrast, but Aleman & Schaeffel (IOVS - 2019)
have just shown that retinal dopamine increases in chicken growing in
environments with ON contrast.

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And finally there is an option in China to use this infrared therapy used
for amblyopia to control myopia progression.

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This is the machine that is used by the child for 3 mins twice a day and
completely arrests myopia progression… this machines is not bought
but rented for the period it is necessary.

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During the years 2000, about 40% of Taiwanese Ophthalmologists were
prescribing some dose of atropine drops for myopia progression. In
recent years they are switching to lower doses.
When stablishing a treatment to arrest progression we must bear in
mind that myopia progresses slowlier as children age. Here we can see
that children aged 6 progress one diopter a year, while those aged 14
only progress half a diopter per year.
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*… and perhaps to adjust the dose?

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For the age the eye stops growing we recommend Hashemi et al.
Clinical and Experimental Ophthalmology (2016) which shows that even
at age 40 myopic eyes continue elongating slightly.
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These are many of the options.

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One has to be cautious when applying experimental data in the clinic.

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