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Myopia: Fundamental understanding needed

Periodic Reporting for period 2 - MyFUN (Myopia: Fundamental understanding needed)

Reporting period: 2018-01-01 to 2019-12-31

In many countries of the world eyes of young people grow too long, developing myopia. Currently, about a third of the world population is myopic but it is expected that half of it will be myopic by 2050. In myopia, distance vision is compromised since the image is focused in front of the retina. Even worse, high degrees of myopia carry a significant risk of blindness for people at the peak of their professional careers, which imposes a severe economic burden to society. There is urgent need to develop preventive strategies for myopia development but many details about its mechanisms are still unknown. Studies have shown that myopia development is tightly linked to tense education and studies, near work and reduced outdoor activity. While studies in animal models have taught a lot about “the visual control of eye growth”, it remains strikingly unclear how exactly the visual experience looks like that accelerates eye growth in children and adolescents. In particular, there are no answers to questions like “If normal eye growth is tightly controlled by visual feedback, why does myopia not limit itself?” or “Why are the effects of new spectacle designs to inhibit myopia so small?” The ETN MyFUN, employing 17 international young scientists, tackled such questions. Their findings were published in international open access journals in currently 25 peer-reviewed articles.
In summary, MyFUN was a very successful network contributing fundamentally to the understanding of myopia and its mechanisms.
While not all questions posed in the beginning could be completely answered, many new facts were learned and there is a long list of new, and partially unexpected, findings that have attracted wide scientific and public interest.
The following major new findings were achieved within the four-year project period: (1) It was found that defocus based on accommodation errors is ignored by emmetropization while defocus imposed by a lens has a strong impact, suggesting that accommodation inaccuracies, which were previously assumed to explain myopia development during extensive reading, have little effect. (2) Rather than accommodation, the visual content of the viewing target seems to trigger myopia. Dark text on bright background should stimulate eye growth while bright text on dark background should have an inhibitory effect. It was also found that the imbalance in the stimulation of retinal ON and OFF channels typical for printed text should be responsible since artificially generated ON or OFF stimuli on a computer screen had similar effects. (3) Explanations were found why some novel spectacle lens designs are not as effective to slow down myopia as hoped. The pattern of peripheral defocus on the retina, which is much more complicated than initially thought, was described in detail and better designs for optical corrections were proposed. (4) Twin studies revealed that the high variability in peripheral refractive errors in children, which would determine how much defocus is imposed with spectacles, was found to be largely genetically determined. Foveal refractive errors are mainly determined by environmental factors. (5) Individual patterns of cone distribution have an effect on refractive errors in chickens, but there is an interaction of the spectrum of ambient light and myopia. Most likely, one can also define light spectra that generate least amounts of myopia in children. (6) When chickens are wearing lenses or diffusers, their fundus reflectivity in UV light increases already after 5 hours before myopia had started to develop. This change is related to thinning of the retinal nerve fibres layer and loss of myelination in certain fibres. Perhaps because defocused retinal images contain less spatial information, the information capacity of the “cables” is adapted. Change in fundus reflectivity in short wavelengths may therefore be a biomarker of myopia. (7) During myopia development, axial eye growth accelerates but the crystalline lens loses power in an attempt to keep the eye at emmetropia. This is achieved by flattening of the lens. However, the cornea does not respond - here nature made a different selection than what humans do when they do refractive surgery. (8) Stimuli for accommodation were better defined - it needs energy in the midspatial frequency range and it can be modulated by adaptation to contrast. Strikingly, myopic subjects require more fine details to start accommodating - they appear less sensitive to defocus. (9) Myopia rates in Chinese school children can be extremely high (> 85% at the age of 12 years) and they can be predicted based on the length of the eye that is measured at early age. (10) The different loss of visual acuity when defocus is in one or the other direction is largely based on higher order aberrations of the optics of the eye. (11) The relationship between photoreceptor alignment (Stiles Crawford effect of first kind) and myopia was analysed and it was found that a marked reduction occurred in myopia. (12) New optical technologies were developed like a device to measure and correct higher order aberrations also in highly myopic subjects which showed that high myopes would see better if the aberrations could be corrected.

MyFUN provided the young researchers with an extensive training programme and with the opportunity to build networks at various meetings and training activities and at international scientific conferences. They set up a myopia blog (https://myopiainscience.wor
MyFUN provided (1) explanations for some not yet understood observations in myopia research, (2) new strategies to slow development of myopia, (3) new technologies for measuring ocular variables related to myopia. The new device to map peripheral refractive error signals will help selecting optical corrections with high potential to slow myopia progression. New techniques have been developed like automated photoreceptor counting, fundal reflectivity measurements, devices for 3D mapping of focus error signals on the retina, or a binocular adaptive optics visual stimulator for high refractive errors (SME Voptica). A potentially large impact will emerge from the finding that text with inverted contrast may have an inhibitory effect on myopia progression. The original publication by Andrea Carrillo Aleman and colleagues was already accessed more than 11,000 times (https://www.nature.com/articles/s41598-018-28904-x).
Generally, new strategies to reduce the incidence and progression of myopia will have a huge socio-economic impact since myopia tends to progress into higher degrees which are associated with increased risks of MMD (“myopic macular degeneration”) already in the mid of the life span.
Apart from working towards a solution of the problem of myopia, young scientists were trained intersectorially at the border of medicine, biology and physics, which increased their employability in industry and academia.
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