Despite increasing research on myopia over the past 30 years, it is clear that myopia is still on the rise in most countries. In fact, in Singapore, Hong Kong, Shanghai, and Taiwan, myopia rates reach 95% and the “high myopias” (> 6D), carrying severe risks of chorio-retinal degeneration and blindness, reach now 20% in young people (i.e. Sun et al, IOVS 2012, 53). In Germany, a recent study shows that persons graduating from high school after 13 years are 51% myopic (Mirshahi et al, Ophthalmology 2014, 121). Myopia is a civilization disease, its recent increase is NOT due to genes, and currently proposed strategies show only small, albeit significant, effects. Therefore, in MyFUN we propose a new effort to answer some fundamental questions of myopia development and consider three targets, grouped in three overlapping research Work Packages (WP).

Work package 1: Unknown features of the visual feedback-control loop for eye growth.

Given that the visual control of eye growth uses a closed loop feedback system, why does myopia development not limit itself and why does undercorrection not reduce its progression? Why does an emmetropic animal eye treated with a positive lens become hyperopic, but a myopic human eye that is not corrected, or undercorrected, does not become less myopic? Why do progressive addition lenses inhibit myopia in children only weakly (20%), bifocals or bifocal contact lenses more (50%) but not completely? We suspect that the role of accommodation in the feedback loop has still not been fully understood and also not sufficiently explored.

Work Package 2: Biological features of the visually-guided signalling cascades controlling eye growth.

While considerable work has been published in animal models to identify the biochemical basis of the signalling cascade that translates the retinal output into thickness changes in the choroid and growth changes in the sclera (Wallman&Winawer, Neuron 2004, 43), neither the exact steps nor the time kinetics are fully explored (Zhu&Wallman, IOVS 2009, 50). Time sampling is limited by the fact that measurements of both transcription rates and proteins require that the animals are sacrificed. Due to the large inter-individual variance, emerging data are highly variable and large numbers of animals are needed. We will get away from collecting average data from many animals but rather study single ones in much more detail than before.

Work Package 3: Visual performance, adaptation and training.

Considerable plasticity is typical for the accommodation mechanism, i.e. subjects reading for only 10 minutes already show a significant shift into more myopic refractions (“nearwork induced transient myopia, NITM”). Such plasticity will affect also the defocus error signal (although NITM should do it in the direction to reduce myopic progression). It is necessary to understand the effects of plasticity of accommodation, visual function during exposure to bifocal vision (supposed to reduce myopia progression), study the sign of defocus dependency of adaptation and develop advanced portable technology to do the required measurements.