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Inhibiting myopia by visual stimulation

Barbara Świątczak

The Research of Barbara Świątczak

During postanal development, eye growth undergoes several changes in order to match optical power of the eye with its axial length. This process is called emmetropization; its main purpose is to reduce refractive error of the eye that is present at birth.  In human infants, as well as in most young animals, refractive error typically is shifted towards hyperopia that usually reaches refraction close to emmetropia within the first year of life1. Unfortunately, process of emmetropization can fail letting the eye grow longer than needed which causes a blurred image on the retina during looking in the distance.

It is known since 1977 2 that the eye growth can be influenced by visual experience what was first shown  in monkeys, and also in other young animals like chickens, guinea pig or tree shrews (Reviews: 3, 4). Since then, it was very clear that an eye has a visually controlled growth mechanism, which is working under an active-feedback loop condition. Moving a focal plane behind the retina by placing negative lens in front of the eye or blurring the retinal image by a diffuser induce axial elongation, choroidal thinning, and myopia development (Figure 1). On the other hand, imposing myopic defocus by placing positive lens in front of the eye strongly inhibits eye growth, inducing prominent increase in choroidal thickness.

Figure 1. Animal models of emmetropization. Hyperopic defocus (imposed by a negative lens) or diffused/blurred retinal image stimulate eye elongation, thinning of the choroid and myopia. Myopic defocus (imposed by a positive lens) generates a shorter eye over time, choroid thickening, and hyperopia.

Searching for in vivo marker of myopia development

During my PhD work, funded by the European Community Research Training Network “MyFUN” at Institute for Ophthalmic Research at University of Tübingen, Germany, I studied the morphological changes in the retina that occur after short-term vision deprivation in chicken model of myopia. The goal was to identify potential biomarkers of myopia development and discover early changes in the retina that could be measured by non-invasive optical procedures. I used custom developed setup to quantify changes in fundus reflectivity which were measured as changes in pupil brightness back-illuminated by the posterior layers of the eye. My setup included a camera and as a source of light, single LED mounted in the center of the camera lens aperture. Since chickens have also ultraviolet vision and ultraviolet-transmitted ocular media, it was possible to measure fundus reflectivity not only in white broadband light but also in near-UV light. I found that vision deprivation imposed by diffusers significantly increases fundus reflectivity in UV light (360nm), with no changes in white light spectrum (peak 500nm) 5. Surprisingly, increased UV reflectivity was detectable already after 5 hours of blurred vision, even before changes in the ocular biometry were noticeable. Fundus reflectivity in UV light continues to rise during eye elongation and progression of myopia 5. To find out the source of increased UV reflectivity, I performed histological studies which revealed that early stages of deprivation myopia were accompanied by exceptional thinning of the retinal nerve fiber layer (RNFL) which contains ganglion cell axons traveling towards optic nerve. Studies with transmission electron microscopy showed axonal shrinkage and loss of myelin sheaths in retinas of deprived eyes, which were the direct cause of the decreased RNFL thickness (Figure 2)6. It has previously been shown in macaque retina that nerve fibers have high reflectivity in light below 400nm 7. I concluded that the progressive loss of myelin during myopia development exposes nerve fibers in RNFL and increases fundus reflectivity in near-UV light, but not at longer wavelengths. Therefore, the increase in UV-reflectivity may be a possible in vivo marker of myopia development in this animal model.

Figure 2. Proposed in vivo marker of myopia development in chicken model. Near-UV, but not white light, fundus reflectivity increases already after 5 hours of vision deprivation, most likely due to the loss of myelin sheaths around ganglion cell axons in the RNFL during myopia development.

Which visual cue drives emmetropization in humans?

Figure 3. Emmetropic eye distinguishes low-pass filtered image from optically defocused images. The retina can trigger significant bidirectional changes in axial length, even when the magnitude of blur was matched (right top). Surprisingly, the myopic retina lost this ability, triggering eye elongation in both cases (right bottom).

Optical defocus as well as low-pass of the retinal image can influence eye growth also in young human subjects. In 2010, Scott Read and colleagues presented a direct evidence that the human visual system is able to detect sign of defocus and move the retina towards the focal plane, similar to what was previously observed in animal models 8. Their work was an inspiration to move my research into human studies. Currently, together with Frank Schaeffel, we form a new Myopia Research Group at the Institute of Molecular and Clinical Ophthalmology (IOB) in Basel, Switzerland. We are focusing on defining visual stimuli that can inhibit axial eye growth and prevent myopia development in kids or slow eye elongation and myopia progression in already existing myopes. Our first goal in that process was to develop software that could implement various spatial, temporal, or chromatic filters to a video file in real-time. This way any movie could be processed through chosen filter and be simultaneously displayed on the screen.  We developed software in Visual C++ that contains different filters like, for instance, filters that overstimulate retinal (and cortical) OFF or ON channels, filters that mimic longitudinal chromatic aberrations, spatial low or high pass filters or chromatic filters. A major advantage of our software is that we can match a modulation transfer function (MTF) of the filter with the MTF of real optical defocus. In our first human study, we tested low-pass movie filtering that acts like a diffuser imposing low-contrast and low-pass on the retinal image, with comparison to optical positive defocus (Figure 3, left). We found that emmetropic eyes were able to distinguish calculated low-pass filter from real optical defocus even when the magnitude of blur was matched (Figure 3, top). Retina in those eyes triggered bidirectional changes in axial length inducing eye elongation after watching low-pass filtered movie and eye shortening when positive lenses were worn9. The same experiment was repeated also in myopic subjects. It turned out that myopic retina was unable to differentiate both condition and always caused eye elongation, which challenges the assumption that undercorrection may be beneficial in near-sighted people (Figure 3, bottom).

In attempt to find a visual stimulation that can inhibit eye growth also in already existing myopes, we performed a “reading experiment”. Near work and education level are strongly correlated with myopia onset and are assumed as high-risk factors of myopia. It was proposed earlier that standard text (dark letters on brighter background) overstimulates the OFF pathway in the retina and induces choroidal thinning, while reading inverted-contrast text (bright letters on darker background) overstimulates the ON pathway causing choroidal thickening10.  We repeated this experiment in myopic subjects, including two different sizes of letters: “small”, whereas the visual angle corresponded to letter size in a text read from a smartphone and “large” with the visual angle corresponded to letter size in a book at reading distance. We showed that the positive effect (eye shortening) of reading inverted-contrast text is also present in myopic subjects (Figure 4). Standard contrast text tends to increase axial eye length, regardless of the size of the text. On the other hand, inverted-contrast texts induce axial shortening, although significantly only when “large” text was presented. Our experiment demonstrated that myopic retina can still respond to certain visual stimuli which might be beneficial in myopia control strategies, but more studies are needed to establish an effective method inhibiting extended eye growth in the long term.

Figure 4. Reading inverted-contrast text (small or large) overstimulates the retinal ON channels and induces eye shortening, while reading standard text (small or large) overstimulates OFF channel causing eye elongation. Larger text (0.6 deg visual angle) was more effective than smaller text (0.2 deg visual angle), inducing significant eye shortening after reading text with inverted contrast.

References

  1. Mutti DO, Mitchell GL, Jones LA, et al. Accommodation, acuity, and their relationship to emmetropization in infants. Optom Vis Sci 2009;86:666-676.
  2. Wiesel TN, Raviola E. Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature 1977;266:66-68.
  3. Norton TT, Siegwart JT, Jr. Animal models of emmetropization: matching axial length to the focal plane. J Am Optom Assoc 1995;66:405-414.
  4. Schaeffel F, Feldkaemper M. Animal models in myopia research. Clin Exp Optom 2015;98:507-517.
  5. Swiatczak B, Feldkaemper M, Schaeffel F. Changes in fundus reflectivity during myopia development in chickens. Biomed Opt Express 2019;10:1822-1840.
  6. Swiatczak B, Feldkaemper M, Schraermeyer U, Schaeffel F. Demyelination and shrinkage of axons in the retinal nerve fiber layer in chickens developing deprivation myopia. Exp Eye Res 2019;188:107783.
  7. Knighton RW, Jacobson SG, Kemp CM. The spectral reflectance of the nerve fiber layer of the macaque retina. Invest Ophthalmol Vis Sci 1989;30:2392-2402.
  8. Read SA, Collins MJ, Sander BP. Human optical axial length and defocus. Invest Ophthalmol Vis Sci 2010;51:6262-6269.
  9. Swiatczak B, Schaeffel F. Emmetropic, But Not Myopic Human Eyes Distinguish Positive Defocus From Calculated Blur. Invest Ophthalmol Vis Sci 2021;62:14.
  10. Aleman AC, Wang M, Schaeffel F. Reading and Myopia: Contrast Polarity Matters. Sci Rep 2018;8:10840.

Barbara Świątczak, PhD

Myopia Research Group
Institute of Molecular and Clinical Ophthalmology Basel (IOB)
Mittlere Strasse 91, CH-4031 Basel, Switzerland

E-mail: barbara.swiatczak[at]iob.ch
Website: www.iob.ch