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Title: Spatial interactive effects on optical defocus : a new mechanism in myopia development
Authors: Chin, Man Pan
Degree: Ph.D.
Issue Date: 2018
Abstract: Introduction: Myopia is mainly due to an excessively increase in axial length. The prevalence of myopia is rocketing upwards especially in east Asia regions. Although myopia can simply be treated by wearing glasses, people with high myopia are prone to various sight-threatening degenerative changes. It is important to understand the mechanism of myopia development and so, the progression of myopia could be controlled. The eye should be similar to other body organs, that possess a homeostatic control to maintain an optimal size. The process is termed emmetropization. Myopia can be regarded as an altered rate of emmetropization, and it is influenced by both genetics and environmental factors. The prevalence of myopia increases in recent decades and it is suspected because of the change of the (visual) environment. Since then, various animal experiments investigated what visual stimuli (inputs) regulate the rate of eye growth (output). Animal experiments from various species provided compelling evidence that the process of emmetropization was guided by optical defocus the eye experienced. There is strong evidence from both animal and human studies suggesting that the eye can detect the sign of defocus. In human study, the retina was hypothesized to detect the signs of defocus, and was tested by using multifocal electroretinogram (mfERG). The human mfERG revealed that, the retinal activities reacted more vigorously to defocus in the peripheral retina than the central retina. However, it is far from clear how the retina can decode defocus. What visual cues does the retina use to decode optical defocus? The visual images are composed of spatial frequencies and the eye possesses various visual channels to decode them. Some animal studies suggested that emmetropization was specially tuned to particular spatial frequencies. It is possible the local detection of defocus at retinal level is also spatially tuned. If the detection of defocus is spatially tuned, spatial frequency can be a regulator for the rate of eye growth in response to optical defocus. In terms of controlling myopia, the spatial composition of the environment surrounding us may be myopiagenic. In this study, we aimed to investigate the changes of human retinal activity to spatial frequencies. Then, the influence of spatial frequency on human retina in responding to optical defocus was investigated. Furthermore, the effects of spatial-defocus interaction on chick myopia development were studied.
Objectives: 1) To investigate how the outer and inner retina responding to spatial frequency by using global flash mfERG; 2) To investigate how the regional activity changes in retina when high and low spatial frequencies are defocused; 3) To investigate the effect of different spatial patterns (high and low spatial frequency) on myopia development in chicks; 4) To investigate the effect of spatial composition with various ratios of spatial frequencies on myopia progression in chicks. Methods: Experiment 1 and 2 were human studies. The human retinal activities were recorded using high contrast Global flash (MOFO) mfERG paradigm. Each cycle of stimulation is consisted of a focal flash (M), followed by a full-screen dark frame (O), a full-screen global flash (F), and another full-screen dark frame (O). This paradigm enhances the activity from the inner retinal neurons, and to separate the outer and inner retinal responses. Two important components, the direct (DC) and induced (IC), reflect the retinal activities from outer and inner retina respectively. In Experiment 1, twenty-four young adults were recruited. Black and white gratings of four spatial frequencies, 0.24, 1.2, 2.4 and 4.8 cycle per degree (cpd) were presented in front of the mfERG stimulation. The amplitudes and implicit times of the DC and IC were pooled into six concentric rings for analysis. Repeated measures analysis of variance (ANOVA) was applied to study the effect of spatial frequency on mfERG responses. In Experiment 2, twenty-three young adults were recruited for mfERG measurement. The setup was similar as in Experiment 1. The retinal electrical responses for low (0.24cpd) and high (4.8cpd) spatial frequency under fully corrected conditions, and of short-term negative defocus (-2D) and short term positive defocus (+2D) conditions were measured. Repeated ANOVA was applied to study the effect of spatial frequency with optical defocus on mfERG response for different retinal regions. Experiment 3 and 4 were animal studies. The visual environment was manipulated to observe the eye growth response in chick. The refractive error in term of spherical equivalent was measured by using Hartinger refractometer. The ocular dimensions including anterior chamber depth, lens thickness, vitreous chamber depth and axial length were obtained by using ultrasound A-scan. In Experiment 3, One eye of normal chicks (10-11 days old) was fitted with a lens-cone device (40mm in length) monocularly and the fellow eye was as the control. At one side of the cone that close to the eye, lenses with powers of +25D, +20D, +15D and +10D were placed. At the other end of the cone, either high spatial frequency visual patterns (0.4mm x 0.4mm black and white checks, 0.9 cpd) or low spatial frequency visual patterns (1.2mm x 1.2mm black and white checks, 0.3 cpd) were used as visual stimuli. The measurements were carried out before wearing the device, on day 4 and day 7 after lens-cone device wearing. The overall effects of spatial frequency and defocus on interocular difference in ocular dimensions and refractive error were tested with two-way ANOVA. In Experiment 4, one eye of normal chicks (10-11 days old) was fitted with a lens-cone device monocularly and the fellow eyes were as the control. The setting and time course was similar to Experiment 3. At the proximal end of the device, a constant hyperopic defocus of -15D would be induced. At the distal end, visual patterns were made by varying the composition of high (H) spatial frequency and low (L) spatial frequency with different ratios by area. (3H1L, 1H1L, 1H3L). A 75:25 ratio by area of high to low spatial checks was denoted as 3H1L, a 50:50 ratio of high to low spatial checks was denoted as 1H1L, and a 25:75 ratio of high to low spatial checks was denoted as 1H3L. The overall effects of SF were tested with one-way ANOVA. Trend analysis by one-way ANOVA was carried out to investigate how varying the spatial composition ratio effect on the interocular ocular growth and refractive error change. Results: In Experiment 1, there was low amplitude DC at low spatial frequency, which increased with increasing spatial frequency, and which decreased with increasing eccentricity. The IC was high in amplitude at all spatial frequencies and reduced in amplitude with increasing eccentricity. In Experiment 2, a significant sign-dependent response to defocus in the DC response was observed. They located mainly in the peripheral retinal regions. The sign dependent response at low spatial frequency was more obvious than that at high spatial frequency, and was located more peripherally. The IC response showed no clear trends for either defocus condition. In Experiment 3, both spatial stimulus and defocus had significant main effects on interocular vitreous chamber depth and on refractive error on day 4 and day 7. Eye growth was significantly faster and more myopic for chicks wearing the device with low spatial visual stimuli than those with high spatial stimuli. In Experiment 4, there was a trend that increase in low spatial composition ratio resulted in more myopic on day 4. The effect became more obvious on day 7 and became significant. Corresponding eyeball elongation was observed as the ratio of low spatial composition increased. Conclusions: This study showed that there was a spatial-defocus interaction, from human retinal activity to myopia progression in chick eye. The mfERG measurement showed that in human retina, the outer and inner retina have different characteristics in processing spatial details. In addition, the peripheral retina could differentiate positive and negative defocus more effectively for low spatial frequencies than the central retina. The human retina was hypothesized to have a decoding system for optical defocus, which was tuned to low spatial frequency, and was located in the retinal near periphery. In chick studies, the results echoed with the human results. The myopia progression induced by hyperopic defocus was shown to depend on spatial stimulus. The rate of compensation to induced hyperopic defocus was higher with low spatial frequency stimulus. In addition, under the same magnitude of hyperopic defocus, trends of increased myopia and ocular elongation were observed when the spatial composition was gradually increased from higher to lower spatial frequency. Various combinations of spatial details influence eye growth even at the same levels of hyperopic defocus. It was speculated that interactive mechanisms between spatial and optical defocus on myopia development may be useful in future to apply for controlling myopia progression.
Subjects: Hong Kong Polytechnic University -- Dissertations
Retina -- Physiology
Pages: xxvi, 198 pages : color illustrations
Appears in Collections:Thesis

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