Eye Growth Research Articles

Impact of repeated low-level red-light therapy on axial length, refraction, and macular retinal blood flow density in adolescents with mild to moderate myopia.

In order to evaluate the effectiveness of repeated low-level red-light (RLRL) therapy on stabilizing axial elongation and refractive changes in adolescents with mild to moderate myopia. In addition, we also examined whether RLRL therapy affects retinal blood flow density in the macular region, a factor previously unstudied in this context. Conducted at a single clinical site, this retrospective, single-arm study followed participants over six months, with assessments at baseline, 1 month, 3 months, and 6 months. The primary outcomes included axial length and spherical equivalent refraction (SER) changes. Secondary assessments included retinal blood flow density (superficial and deep macular layers), white-to-white corneal diameter, central corneal thickness, intraocular pressure (IOP), corneal curvature, light sensitivity, and peripheral retinal thickness. There were 32 enrolled participants (mean age = 11.5 ± 1.72) in the current study. The spherical equivalent (SER) remained relatively stable over the first three months, but it significantly improved at six months, changing from -2.39 ± 2.21 D at baseline to -2.01 ± 2.12 D (P < 0.05). However, the axial length also showed minimal variation across follow-up visits, indicating stable eye growth with no substantial elongation throughout the study period. Furthermore, RLRL therapy resulted in stable measurements across primary and secondary outcomes (all P > 0.05), with no significant changes over the six months. There were no obvious side effects following the treatment. Low-energy red light therapy shows promise as a non-invasive approach for stabilizing myopia in adolescents, with no observed compromise to retinal blood flow density. Further longitudinal research is needed to validate these findings and support clinical recommendations for myopia management.

Axial Growth and Myopia Progression After Discontinuing Soft Multifocal Contact Lens Wear

For myopia control to be beneficial, it would be important that the benefit of treatment (slowed eye growth) is not lost because of faster than normal growth (rebound) after discontinuing treatment. To determine whether there is a loss of treatment effect (rebound) after discontinuing soft multifocal contact lenses in children with myopia. The Bifocal Lenses in Nearsighted Kids 2 (BLINK2) cohort study involved children with myopia (aged 11-17 years at BLINK2 baseline) who completed the BLINK Study randomized clinical trial. Enrollment was from September 2019 through January 2021; follow-up was completed in January 2024. In the BLINK2 Study, all children wore high-add (+2.50 diopter [D]) multifocal soft contact lenses for 2 years and single-vision soft contact lenses during the third year to determine if rebound occurred. High-add multifocal soft contact lenses and single-vision soft contact lenses. Eye length (optical biometry) and refractive error (cycloplegic autorefraction) were measured annually. Of 248 participants enrolled in BLINK2, 235 completed the study. The median age at the baseline visit was 15 years (range, 11-17 years); 146 participants (59%) were female, and 102 (41%) were male. At baseline for BLINK2, mean (SD) axial length and spherical equivalent refractive error were 25.2 (0.9) mm and -3.40 (1.40) D, respectively. After participants switched from multifocal to single-vision contact lenses, axial elongation increased by 0.03 mm per year (95% CI, 0.01 to 0.05) regardless of their original BLINK treatment assignment (P = .81). There was also an increase in myopia progression after switching to single-vision lenses of -0.17 D per year (95% CI, -0.22 to -0.12) that did not depend on the original BLINK treatment assignment (P = .57). There continued to be a difference in axial length and refractive error throughout BLINK2 based on the BLINK Study treatment assignment with the original high-add group having shorter eyes and less myopia than the original medium-add (+1.50 D) and single-vision groups. The BLINK2 Study found no evidence of a loss of treatment effect after discontinuing multifocal contact lenses in older teenagers. These data suggest eye growth and myopia progression returned to faster but age-expected rates and support continuing multifocal lenses until cessation of elongation and progression.

Meta-analysis of retinal transcriptome profiling studies in animal models of myopia.

Myopia prevalence is increasing at alarming rates, yet the underlying mechanistic causes are not understood. Several studies have employed experimental animal models of myopia and transcriptome profiling to identify genes and pathways contributing to myopia. In this study, we determined the retinal transcriptome changes in response to form deprivation in mouse retinas. We then conducted a transcriptome meta-analysis incorporating all publicly available datasets and analyzed how the results related to the genes associated with refractive errors in human genome-wide association studies (GWAS). Form deprivation was induced in three male C57BL6/J mice from postnatal day 28 (P28) to P42. Retinal gene expression was analyzed with RNA sequencing, followed by differential gene expression analysis with DESeq2 and identification of associated pathways with the Kyoto Encyclopedia of Genes and Genomes (KEGG). A systematic search identified four similar retinal transcriptomics datasets in response to experimental myopia using chicks or mice. The five studies underwent transcriptome meta-analyses to determine retinal gene expression changes and associated pathways. The results were compared with genes associated with human myopia. Differential gene expression analysis of form-deprived mouse retinas revealed 235 significantly altered transcripts, implicating the BMP2 signaling pathway and circadian rhythms, among others. Transcriptome-wide meta-analyses of experimental myopia datasets found 427 differentially expressed genes in the mouse model and 1,110 in the chick model, with limited gene overlap between species. Pathway analysis of these two gene sets implicated TGF-beta signaling and circadian rhythm pathways in both mouse and chick retinas. Some pathways associated only with mouse retinal changes included dopamine signaling and HIF-1 signaling pathway, whereas glucagon signaling was only associated with gene changes in chick retinas. The follistatin gene changed in both mouse and chick retinas and has also been implicated in human myopia. TGF-beta signaling pathway and circadian entrainment processes were associated with myopia in mice, chicks, and humans. This study highlights the power of combining datasets to enhance statistical power and identify robust gene expression changes across different experimental animal models and conditions. The data supports other experimental evidence that TGF-beta signaling pathway and circadian rhythms are involved in myopic eye growth.

Broadband Long Wavelength Light Promotes Myopic Eye Growth and Alters Retinal Responses to Light Offset in Chick.

Prolonged exposure to broadband light with a short-wavelength (blue) or long-wavelength (orange/red) bias is known to impact eye growth and refraction, but the mechanisms underlying this response are unknown. Thus, the present study investigated the effects of broadband blue and orange lights with well-differentiated spectrums on refractive development and global flash electroretinography (gfERG) measures of retinal function in the chick myopia model. Chicks were raised for 4 days with monocular negative lenses, or no lens, under blue, orange, or white light. Chick weight, eye dimensions, and refraction were measured at the conclusion of rearing. In a separate cohort of chicks, the effect of 4 days of colored light rearing on retinal responses to orange, blue, or white light flashes was assessed using gfERG. Chicks reared under orange light for 4 days exhibited a significantly larger myopic shift in response to negative lenses compared to those reared under blue light. Orange light rearing for 4 days increased the gfERG d-wave amplitude and implicit time in response to orange light flashes but did not alter responses to white or blue flashes. Blue and white light rearing did not affect the retina's response to light flashes of any color. Orange light rearing exacerbated defocus-induced myopia relative to blue light rearing. The gfERG recordings revealed that prolonged orange light exposure increased retinal responsivity to the offset of long wavelength light flashes, suggesting a potential role for ON/OFF pathway balance in generating the refractive response that requires further electrophysiological and molecular investigation.

Insights into myopia from electrophysiology and from rare inherited retinal diseases

Eye growth is driven by retinal signalling. The first part of the talk will discuss a common genetic myopia‐risk polymorphism near the GJD2 gene and recent findings that have found an association between allelic identity at this locus and retinal cone‐driven OFF pathway responses as detected in the full‐field electroretinogram (ERG). Results will be presented from investigations of standard and experimental ERG protocols and also from analysis of ERG components that are not conventionally quantified. The second part of the talk will present axial length distributions in a range of rare monogenic retinal diseases. These distributions will be compared with reference datasets and possible insights into mechanisms of emmetropisation will be discussed.

Peripheral defocus spectacle lenses versus single‐vision spectacle lenses for myopia control: Systematic review and meta‐analysis

Aims/Purpose: Myopic children wearing traditional single‐vision lenses (SVL) will continue to increase in nearsightedness as eye growth occurs. However, peripheral defocus lenses (PDL) are specialized spectacles based on the retinal‐defocus theory, designed to slow down the progression of myopia. Therefore, we aimed to perform a meta‐analysis exploring the effectiveness of PDL and SVL in controlling myopia.Methods: We searched PubMed, Embase, Cochrane, Web of Science, Epistemonikos and BVS for studies comparing the PDL to SVL in children and adolescents with myopia. Outcomes were spherical equivalent refraction (SER) and axial length (AL). The RoB 2 tool was used to assess the risk of bias.Results: We included 673 patients from 5 randomized clinical trials. PDL was used to control myopia in 403 (59,9%) patients. The mean age was 9.4 years old. Follow‐up ranged from 6 to 12 months. In the pooled analysis, the SER (RR 4.41; 95% CI 1.76, 11.08; I2 = 0%) and AL (RR 28.10; 95% CI 5.57, 141.58; I2 = 18%) was lower in patients using PDL compared to SVL. In the segment analysis, all segments showed a deceleration of the SER of PDL when compared to SVL. The 6 month was the only one to show a result with low heterogeneity (WMD ‐0.19; 95% CI ‐0.26, ‐0.13; I2 = 21%). The analysis at 12 months showed substantial heterogeneity (WMD ‐0.35; 95% CI ‐0.44, ‐0.26; I2 = 57%). When analyzing AL, it can be seen that PDL grows less than SVL in all the segments analyzed. The differences between 6 months (WMD 0.11; 95% CI 0.22, 0.19; I2 = 88%) and 12 months (WMD 0.14; 95% CI 0.10, 0.17; I2 = 70%) were small and with significant heterogeneity.Conclusions: PDLs were associated with more effectiveness at slowing down the progression of myopia, as assessed by both spherical equivalent and axial growth. The substantial heterogeneity between the studies suggests the need for additional research without conflict of interest bias to confirm these results and understand the variations in the effects of the different PDL designs.

Two‐year changes of macular choroidal thickness in response to 0.01% atropine eye drops: Results from the myopia outcome study of atropine in children (MOSAIC) clinical trial

AbstractPurposeTo investigate 2‐year changes in macular choroidal thickness (ChT) in children receiving 0.01% atropine eyedrops and its relationship with spherical equivalent refraction (SER) progression and axial length (AL) elongation.MethodsA total of 250 myopic children aged 6–16 years (167%–0.01% atropine, 83‐placebo) were enrolled in the MOSAIC (ISRCTN36732601) clinical trial. Participants with complete 2‐year ChT (Topcon Triton Swept‐Source OCT), SER, and AL data were included in this study. Changes in macular ChT at 2 years and associations with changes in SER and AL elongation were analysed using linear mixed models.ResultsA total of 187 children (126%–0.01% atropine, 61‐placebo) were included in the analysis. Choroidal thickness over 2 years was stable in the 0.01% atropine compared with placebo group, which exhibited consistent thinning in subfoveal (mean ± SE: 0.49 ± 2.22 μm vs. −9.46 ± 2.69 μm; p = 0.034), parafoveal (1.40 ± 1.73 μm vs. −8.11 ± 2.08 μm; p = 0.002), and perifoveal (0.80 ± 1.25 vs. −6.17 ± 1.69; p = 0.002) macular subfields. Choroidal thickening was observed in participants with slower axial eye growth and myopia progression, regardless of their treatment group. Mediation analysis indicated that atropine 0.01% had a significant effect on ChT, with 68.3% of the effect being direct and 31.7% mediated through axial length changes. For SER, the direct effect on ChT was 80%, with the remaining 20% mediated by SER changes.ConclusionsMyopic participants treated with 0.01% atropine exhibited stable ChT over 2 years, whereas the placebo group showed consistent thinning. The effect of atropine 0.01% on ChT was only partially explained by axial length and SER changes, indicating a direct effect of atropine treatment on the choroid.

Experimental Myopia Results in Peripapillary Ganglion Cell and Astrocyte Reorganization with No Functional Implications During Early Development.

Myopic eye growth induces mechanical stretch, which can lead to structural and functional retinal alterations. Here, we investigated the effect of lens-induced myopic growth on the distribution of retinal ganglion cells (RGCs), glial fibrillary acidic protein (GFAP) expression and intensity, and peripapillary retinal nerve fiber layer (ppRNFL) thickness in common marmosets (Callithrix jacchus) induced with myopia continuously for six months, using immunohistochemistry and spectral-domain optical coherence tomography. We also explored the relationship between cellular structural parameters and the photopic negative response (PhNR) using full-field electroretinography. Marmosets induced with myopia for six months developed axial myopia, had a thinner ppRNFL, reduced peripapillary ganglion cell (≈20%) and astrocyte density (≈42%), increased panretinal GFAP expression (≈42%) and nasal mid-periphery staining intensity (≈81%) compared to age-matched controls. Greater degrees of myopia and vitreous elongation were associated with reduced peripapillary RGCs and astrocyte density, and increased GFAP expression and intensity. These cellular structural changes did not show a significant relationship with the features of the PhNR, which remained unchanged. The outcomes of this study suggest that myopia induces a reorganization of the peripapillary inner retina at the cellular level that may not result in measurable functional repercussions at this stage of myopia development.

EFEMP1 contributes to light-dependent ocular growth in zebrafish.

Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicates efemp1 in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modify efemp1 expression specifically in the retina of zebrafish. We found that under normal lighting, efemp1 mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function. Efemp1 modification changed the expression of efemp1, egr1, tgfb1a, vegfab and rbp3 genes in the eye, and changed the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins. Efemp1 modification also impacted dark-rearing-induced responses of vegfab and wnt2b genes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated by efemp1.

Modulation of all- trans retinoic acid by light and dopamine in the murine eye.

Ambient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All- trans retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retino-scleral signaling cascade underlying myopic eye growth. However, how ocular atRA responds to different lighting and whether atRA and DA interact remains unknown. Dark-adapted C57BL/6J mice (29-31 days old) were exposed to Dim (1 lux), Mid (59 lux), or Bright (12,000 lux) ambient lighting for 5-60 minutes. Some mice were also systemically administered the DA precursor, LDOPA, or atRA prior to light exposure. After exposure, the retina and the back-of-the-eye (BOE) were collected and analyzed for levels of atRA, DA, and the DA metabolite, DOPAC. DA turnover (DOPAC/DA ratio) in the retina increased in magnitude after only five minutes of exposure to higher ambient luminance but was minimal in the BOE. In contrast, atRA levels in the retina and BOE significantly decreased with higher ambient luminance and longer duration exposure. Intriguingly, LDOPA-treated mice had a transient reduction in retinal atRA compared to saline-treated mice, whereas atRA treatment had no effect on ocular DA. Ocular atRA was affected by the duration of exposure to different ambient lighting and retinal atRA levels decreased with increased DA. Overall, these data suggest specific interactions between ambient lighting, atRA, and DA that could have implications for the retino-scleral signaling cascade underlying myopic eye growth.

Effects of computer-generated patterns with different temporal and spatial frequencies on choroidal thickness, retinal dopamine and candidate genes in chickens wearing lenses

PurposeChanges in choroidal thickness (ChT) are proposed to predict myopia development but evidence is mixed. We investigated time courses of choroidal responses, following different types of dynamic artificial stimulation in chicks with and without spectacle lenses, as well as changes in retinal dopamine metabolism and expression of candidate genes.MethodsChicks were kept in an arena surrounded by computer monitors presenting dynamic checkerboard fields of small, medium and large size. Fields were displayed with different cycle frequencies, as ON (rapid rise, slow decay) or OFF (slow rise, rapid decay) temporal luminance profile. Refractive errors, ocular biometry and ChT were assessed. Dopamine metabolism and candidate gene expression levels were also measured. Stimuli were applied for (1) 3 h with no lens, (2) 3 h and monocular treatment with −7D or +7D lenses, (3) 3 or 7 days.Results(1) The smallest fields caused the largest decrease in ChT. (2) Negative lens treatment induced on average 11.7 μm thinner choroids. ChT thinning was enhanced by 10 Hz-ON medium field size flicker which also reduced choroidal thickening with positive lenses. (3) With prolonged treatment, the choroid recovered from initial thinning in all groups although to varying degrees which were dependent on stimulus parameters. Relative ChT changes were positively correlated with the vitreal level of dopamine metabolites. Retinal EGR-1 mRNA level was positively correlated with choroidal thickness. Retinal melanopsin mRNA was increased by 10 Hz-ON stimulation and choroidal BMPR1A mRNA increased with 10 Hz-OFF stimulation. On average, early choroidal thinning did not predict the amount of negative lens-induced eye growth changes after 7 days, whereas later ChT changes showed a weak association.ConclusionNegative lenses caused long-lasting choroidal thinning, with some recovery during lens wear, especially after stimulation with 10 Hz. The dynamic stimuli modulated choroidal thinning but effects were small. There was little difference between ON and OFF stimulation, perhaps because the checkerboard patterns were too coarse. 10 Hz cycle frequency increased dopamine release. Less dopamine was correlated with thinner choroids. Result do not exclude a predictive value of choroidal thickening for future refractive development since we almost exclusively tested choroidal thinning effects.

The concept of cone opponency may extend beyond accommodation, to myopiagenesis and emmetropization, for a better peripheral defocus lens.

Myopia has ever-rising prevalence in the past few decades globally. Its pathogenesis is still not adequately elucidated especially at the signal transduction level. For the environmental risk factors, there is a large body of fragmented knowledge about the visual inputs for accommodation, myopiagenesis and emmetropization, with the latter two being essentially local processes. The red-green and yellow-blue chromatic pathways, together with the underlying L-M and S-(L+M) cone opponency, seem to be the common denominator amongst them. In this review, experimental and observational evidence are summarized to delineate the interplay of them. This review may establish the pivotal role of longitudinal chromatic aberration (LCA) for a mechanistic approach to future research in myopia control. This review looks into the mechanistic processes underlying myopiagenesis and emmetropization, specifically focusing on chromatic aberration and cone opponency in vision as pivotal components. The roles of longitudinal chromatic aberration (LCA) and cone contrast in myopia onset and development are intriguing. How visual input and chromatic pathways (specifically, red-green and blue-yellow cone opponency) contribute to accommodation that may trigger emmetropization mechanisms, thereby influencing eye growth patterns are explored and discussed. In brief, this manuscript delves into the physiology of visual processing and highlights a foundational aspect of visual science that may account for a "Go" or "Stop" signaling in axial eye growth. It further proposes a metric to gauge myopia-inhibiting optical devices such as the peripheral defocus lenses, for its best iteration. Future research in the above-mentioned areas is warranted.

Impact of Forms of Visual Attenuation on Short-Term Eye Changes Under Controlled Reading Visibility.

Animal studies have suggested that visual degradation impacts eye growth due to the attenuation of high spatial frequencies. However, the influence of perceptual visibility remains unclear in humans. The aim of this study was to investigate the impact of visibility on visual attenuation-related eye changes during reading. Axial length (AxL) and choroidal thickness (ChT) changes associated with reading tasks were measured in two separate experiments. In the first experiment, the reading task was conducted under different forms of visual attenuation (contrast, resolution, defocus, noise, and crowding). For each form of visual attenuation, the text was set at a sub-threshold level of visibility, evaluated via prior measurement of reading performance, and kept constant via adaptive control of the intensity of the stimulation. Each sub-threshold reading condition was compared with a supra-threshold reading text, serving as control. In the second experiment, the effect of visibility on lens-induced defocus was further examined by comparing the effect of text stimulation with an equivalent dioptric of 5.5 D under sub- and supra-threshold levels of resolution. Near distance reading with supra-threshold texts caused eye elongation (AxL: +12.942 µm ± 2.147 µm; ChT: -3.192 µm ± 1.158 µm). Additional defocusing failed to exacerbate axial elongation under sub-threshold text visibility (mean difference: -0.135 µm ± 2.783 µm), revealing a clear inhibitory effect of lowering visibility on eye changes. Other forms of visual degradation, including crowding (mean difference: 6.153 µm ± 2.127 µm) and noise (mean difference: 5.02 µm ± 2.812 µm) also showed an inhibitory effect on eye elongation. The significant effect of crowding indicated that post-retinal mechanisms, involving attentional processes related to crowded characters, may play a role in the influence of visibility. Although the featural composition of visual stimulation can drastically influence eye changes, this study revealed an important mediating role of visibility, previously underscored in chick studies, which warrants further explorations of the impact of post-retinal processes in eye growth.

In vivo retinal melanin detection with the calibrated depolarization index in polarization-sensitive optical coherence tomography.

A data-based calibration method with enhanced depolarization contrast in polarization-sensitive optical coherence tomography (PS-OCT) was developed and demonstrated effective for detecting melanin content in the eye. We aim to mitigate the dependence between the measured depolarization metric and the intensity signal-to-noise ratio (SNR) for improved visualization of depolarizing tissues, especially in low SNR regions, and to demonstrate the enhanced depolarization contrast to evaluate melanin presence. A function for calibrating the depolarization metric was experimentally derived from the young albino guinea pig, assuming depolarization free in the retina. A longitudinal study of guinea pigs (9 weeks) was conducted to assess the accumulation of melanin during early eye growth. Furthermore, the melanin content of the sub-macular choroid was compared in eyes with light and dark irides involving 14 human subjects in early middle adulthood. We observed an increase in the improved depolarization contrast, which indicates potential melanin accumulation in the early eye development with age in the pigmented guinea pig eyes. We found a significant difference in melanin content between human eyes with light and dark colors. Our proposed calibration method enhanced the visualization of depolarizing structures in PS-OCT, which can be generalized to all kinds of polarization-sensitive imaging and can potentially monitor melanin in healthy and pathological eyes.

Update on central factors in myopia development beyond intraocular mechanisms.

Myopia, a prevalent refractive error, primarily affects children and adolescents, characterized by excessive axial elongation causing distant objects to focus in front of the retina. This review explores the intricate mechanisms beyond intraocular factors, emphasizing the significant role of central factors in myopia development and progression. Intraocular mechanisms involving the retina, RPE/choroid, and sclera are well documented, with these structures playing crucial roles in eye growth regulation. Central factors, including brain structure and function alterations, are increasingly recognized, supported by advanced imaging techniques such as fMRI and rs-fMRI. Clinical findings highlight changes in brain activity and connectivity in high myopia (HM), suggesting neural plasticity or compensatory mechanisms. Animal studies further elucidate central mechanisms, indicating the involvement of specific brain nuclei like the visual cortex and suprachiasmatic nucleus. Understanding these complex interactions between intraocular and central mechanisms is crucial for developing novel therapeutic strategies to inhibit myopia progression and prevent associated complications. This review aims to provide a comprehensive analysis of current research, contributing to a deeper understanding of central factors of myopia.

Choroid vascular index in myopic patients - A mini review.

Myopia has become a globally prevalent ocular disease. The choroid plays a vital role in myopia, and its changes tend to occur earlier than those of the retina and long-term variations in eye growth. Abnormal axial growth is an intrinsic characteristic of myopia, accompanied by ocular biomechanical changes that result in chorioretinal atrophy, thinning, and other complications particularly in the choroidal vasculature. Recent advancements in imaging technologies have provided deeper insights into these changes. This article explores key findings related to the choroid vascular index in myopia patients.

Refractive development II: Modelling normal and myopic eye growth.

During refractive development, eye growth is controlled by a combination of genetically pre-programmed processes and retinal feedback to minimise the refractive error. This work presents a basic differential model of how this process may take place. The description starts from two bi-exponential descriptions of the axial power Pax (or dioptric distance) and total refractive power Peye, the difference between which corresponds with the spherical refractive error S. This description is rewritten as an ordinary differential equation and supplemented by a retinal feedback function that combines retinal blur (closed loop) with a term describing excessive axial growth (open loop). This model is controlled by a total of 18 parameters that allow for a wide variety of developmental behaviours. The proposed model reproduces refractive development growth curves found in the literature for both healthy and myopic eyes. An early onset of myopisation, a large growth term and a high minimum for the crystalline lens power all lead to higher degrees of myopia. Assigning more importance to the feedback than to the pre-programmed growth makes the model more sensitive to myopogenic influences. Applying refractive corrections to the model, undercorrection is found to produce more myopia. The model compensates for a low-powered imposed lens and can return to (near) emmetropia if that imposed lens is removed quickly thereafter. Finally, simulating the effect of a diffuser leads to high myopia. Using a series of basic assumptions, the proposed model recreates many well-known experimental and clinical results about refractive development from the literature while placing them in a standardised context. This contributes to a broader understanding of the origins of refractive errors, and future versions may help in the development of solutions for myopia control.

Retinal "sweet spot" for myopia treatment.

We studied which retinal area controls short-term axial eye shortening when human subjects were exposed to + 3.0D monocular defocus. A custom-built infrared eye tracker recorded the point of fixation while subjects watched a movie at a 2m distance. The eye tracker software accessed each individual movie frame in real-time and covered the points of fixation in the movie with a uniform grey patch. Four patches were programmed: (1) foveal patch (0-3 degrees), (2) annular patch (3-9deg), (3) foveal patch (0-3deg) combined with an annular patch (6-9deg), and (4) full-field patch where only 6-10deg were exposed to the defocus. Axial eye shortening was elicited similarly with full-field positive defocus and with the foveal patch, indicating that the fovea made only a minor contribution (-11 ± 12μm vs. -14 ± 17μm, respectively, n.s.). In contrast, patching a 3-9 degrees annular area or fovea together with an annular area of 6-9 degrees, completely suppressed the effect when compared with full-field defocus (+ 3 ± 1μm or -2 ± 13μm vs. -11 ± 12μm, respectively, p < 0.001). Finally, we found that the near-peripheral retina (6-10 degrees) is a "sweet spot" for positive defocus detection and alone can regulate eye growth control mechanism, and perhaps long-term refractive development (-9 ± 8μm vs. full-field: -11 ± 12μm, n.s.).

Quantitative structural organization of the sclera in chicks after deprivation myopia measured with second harmonic generation microscopy.

Visual deprivation causes enhanced eye growth and the development of myopia, which is associated with a change in the arrangement of collagen fibers within the sclera. A second harmonic generation (SHG) microscope has been used to image the collagen fibers of unstained scleral punches from the posterior part of chicken eyes. We aimed to analyze the fibrous scleral tissue and quantify the changes in collagen organization in relation to the extent of induced deprivation myopia. The scleral architecture was assessed with the Radon transform (RT) through the parameter called structural dispersion (SD) that provides an objective tool to quantify the level of organization of the collagen network. We found that final refraction and axial length changes were linearly correlated. However, no significant differences in scleral thickness were found for different amounts of induced myopia. In contrast, a significant correlation between SD and refraction was demonstrated, ranging from a non-organized (in the control sclerae) to a quasi-aligned distribution (with a dominant direction of the fibers, in the sclera of myopic chicks). These findings demonstrate a remodeling process of the scleral collagen associated with myopia progression that can be measured accurately combining SHG imaging microscopy and RT algorithms.

OPTICAL BLUR AFFECTS DIFFERENTLY ON AND OFF VISUAL PATHWAYS.

The human eye has a crystalline lens that focuses retinal images at the point of fixation. Outside this fixation region, images are distorted by optical blur, which increases light scatter and reduces the spatial resolution and contrast processed by neuronal pathways. The spectacle lenses that humans use for optical correction also minify or magnify the images, affecting neuronal surround suppression in visual processing. Because light and dark stimuli are processed with ON and OFF pathways that have different spatial resolution, contrast sensitivity and surround suppression, optical blur and image magnification should affect differently the two pathways and the perception of lights and darks. Our results provide support for this prediction in cats and humans. We demonstrate that optical blur expands ON receptive fields while shrinking OFF receptive fields, as expected from the expansion of light stimuli and shrinkage of dark stimuli with light scatter. Spectacle-induced image magnification also shrinks OFF more than ON receptive fields, as expected from the stronger surround suppression in OFF than ON pathways. Optical blur also decreases the population response of OFF more than ON pathways, consistent with the different effects of light scatter on dark and light stimuli and the ON-OFF pathway differences in contrast sensitivity. Based on these results, we conclude that optical blur and image magnification reduce the receptive field sizes and cortical responses of OFF more than ON pathways, making the ON-OFF response balance a reliable signal to optimize the size and quality of the retinal image.