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hypothesis based on the distribution of photon catch along the length of the photoreceptor outer segments.
If chromaticity of incident light is a factor influencing ocular and refractive development, it could also be an explanation for the myopic shift in refraction noted among adult microscopists, for hematoxylin and eosin staining commonly used in stained sections has a large red content but also a sufficient content of other wavelengths to ensure the focus of midlength wavelengths in the mid-points of M-cone photoreceptor outer segments. With a preponderance of red wavelengths, there would be a skewed distribution of photons in the outer segments in favor of the distal portions of the L-cone outer segments that we hypothesise leads to axial elongation of the eye and myopia.
Currently, although there is evidence that ocular and refractive development can be influenced by a large number of physical attributes of the light incident upon the eye, including intensity, spatial and temporal frequency, contrast, photoperiodicity, vergence of incident light and chromaticity, the mechanisms underlying the development of myopia as a result of these effects remain largely unexplained. There is a probability that the influence of these various factors on ocular growth and refraction is multifactorial just as the genetic contribution is thought to be polygenic.
In relation to chromaticity, we have proposed a hypothesis to explain the role that photon distribution in the photoreceptor outer segments may have in ocular development and the resulting refractive state. Even if the hypothesis, as we believe to be the case, proves to be supportable, the mechanisms by which an abnormal distribution of photons along the outer segments of photoreceptors can influence ocular growth remain to be elucidated.
Therapeutic implications
The physical factors that have been identified as playing a role in the development of myopia are non-specific blurring of the retinal image, the intensity of light reaching the eye and as yet undetermined factors related to outdoor activity. The influence of spatial frequency of the light reaching the retina and the periodicity of exposure is much less obvious. We advance the hypothesis that ocular development in the young eye is governed by the distribution of photon catch in the photoreceptor outer segments and if this is the case, there are a number of strategies that might be considered in terms of therapeutic intervention. The simplest therapeutic option is to
379 Physical Factors in Myopia and Potential Therapies
ensure that children are involved in as much outdoor activity as possible, and additionally, that the amount of time spent in conditions of artificial lighting is curtailed.
In the development of therapeutic interventions that might prevent the onset of myopia or slow its progression, randomised trials of chromatic manipulation of light incident on the eyes by appropriate modification of school or home lighting, the wearing of spectacles with appropriate transmission characteristics and so on, are not only required but are currently underway.
The development of potential therapies would be greatly aided by a better understanding of the biological and biochemical events that may be induced by the hypothesised effect of an inappropriate photon catch distribution in photoreceptor outer segments, and to this end, more experimental work is necessary to elucidate the exact roles that specific combinations of differing wavelengths of light may have on the retina.
Apart from modification of the chromaticity of light to which the developing eye is exposed, it is theoretically possible to change the pattern of photon catch in photoreceptor outer segments by optical means not involving chromaticity. Thus, under-correction of myopia or the wearing of plus lenses should advance the focal plane of light entering the eye but decrease the vergence of light passing through the retina. This, in turn, should favor an increased photon catch in the proximal ends of the photoreceptor outer segments as compared with the distal ends.
The effect of under-correction of myopia or the wearing of plus lenses, however, is likely to be much less effective than appropriate chromatic manipulation. In conditions of white light (daylight) viewing, a proportion of longer wavelength red light will be focused not in the photoreceptor outer segments but behind the retina. As a result under-correction of myopia or the use of low power plus lenses will not affect the relative photon catch in the tips and bases of the outer segments, unless the lenses were strong enough to move the focal plane for longer wavelength red light sufficiently far forward to leave the tips of the outer segments unstimulated. Lenses of sufficient strength to shift focus far enough forwards would cause significant blurring of vision and would not be tolerated for continuous wear. The use of progressive addition lenses has been claimed to slow myopia progression in some children,81 but in uncontrolled trials in Australia and Singapore, the wearing of plus lenses of +3.00 D for a short period during the day instead of their usual correction for myopia, failed to slow the progression of myopia in most myopic children treated. A
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study82 in which one eye of myopic children was corrected for distance and the other uncorrected or under-corrected to keep a refractive imbalance between eyes of 2.00D showed that for reading, children accommodated with the distance corrected eye and the under-corrected eye accommodated to the same extent. The under-corrected eye suffered myopic defocus from the combined effects of an under-corrected refractive error and the imposed accommodation to match that of the fully corrected eye. This myopic defocus of the under-corrected eye was shown to be sufficient to slow the rate of myopia progression in the under-corrected eye. I.e. the under-corrected eye benefitted from the equivalent of wearing a plus two dioptre lens but only when a degree of accommodation was also present sufficient to ensure significant myopic defocus. The myopic defocus would result in divergence of light passing through the retina that among other effects would be likely to alter the distribution of photon catch in the outer segments in favour of an increased photon catch in the bases of the S- cones.
Of all the factors inducing myopia that might be subject to manipulation to reduce the progression of myopia or prevent its development, optical and chromatic factors would appear to offer some hope of therapeutic application. In activities such as reading, measures to ensure that in addition to sharp focus of the reading material in the plane of interest there is also a proportion of visual content from a further distance, if this could be achieved, might be one approach.
As regards chromatic manipulation if the hypothesis we have advanced can be supported by further work, modification of ambient lighting to reduce its red content and increase the relative content of blue wavelengths with the preservation of some mid-wavelength green would be worth investigating as a therapeutic option.
As already indicated, current therapies for myopia are mainly aimed at correcting the optical effects of myopia by correcting lenses or by refractive surgery. Although of benefit, they do not address the underlying pathology of the condition that carries with it a number of potentially sight-threatening complications.
The use of topically applied muscarinic receptor blocking agents such as atropine is undoubtedly effective in preventing scleral elongation and so reducing the progress of myopia. Atropine, however, carries the disadvantage of paralyzing accommodation and dilating of the pupil, with resultant photophobia in bright light and an unknown and possibly adverse effect on the retina from a long-term increase in light exposure.