Role In Refractive Development Research Articles

Ocular biometry characteristics and its relationship with age, gender, spherical equivalent in Turkish children.

Studying ocular biometric parameters in different populations and determining the relationship with personal characteristics can provide valuable information about ocular growth and help provide a better understanding of refractive errors. To describe distributions of ocular biometry and to evaluate its associations with age, gender, spheric equivalent in Turkish children. In this prospective study 344 children aged 3-14 years were evaluated. Parameters studied included axial length (AL), anterior chamber depth (ACD), and mean corneal radius (CR) measured with optical biometry. Cycloplegic refraction values were obtained using autorefractometer. The change of biometric parameters according to age and gender were evaluated. The relationship between ocular biometry parameters with refraction and age was analyzed by linear regression. Mean spherical equivalent (SE), AL, ACD and AL/CR observed to be lowest in the preschooler group (P < 0.001). SE reduced with age, and a weak correlation observed between SE and age (r = -0.333). AL and ACD had moderate and weak positive correlations with age respectively (r = 0.511; r = 0.304). There were negative correlations between SE with AL, ACD and AL/CR (r = -0.826; r = -0.540; r = -0.886). The strongest correlation with SE among these parameters was identified for AL/CR. AL and ACD were higher in boys, while the CR was lower in girls (p < 0.001). While AL in children in late schooler group is higher than European countries, it shows similar characteristics in early schooler group. In addition AL is lower in all age groups than Asian population sexcept preschooler group. With age AL increases, SE decreases and AL plays a key role in refractive development.

Retinal Transcriptomics Analysis Reveals the Underlying Mechanism of Disturbed Emmetropization Induced by Wavelength Defocus

Purpose Wavelength signals play a vital role in refractive development. This study aimed to explore the retinal transcriptome signature in these processes. Methods Guinea pigs were randomly divided into three groups exposed to white, blue, or green environmental light for eight weeks. Refraction and axial length were evaluated every 4 weeks, and the retinal transcriptome was profiled at 8 weeks. Results Compared with the white group, ocular refraction significantly decreased and ocular axial length significantly extended in the green group whereas these parameters showed opposite trends in the blue group. RNA-sequencing showed that, compared with the white group, 184 and 171 differentially expressed genes (DEGs) were found in the blue and green groups, respectively. Among these DEGs, only 31 overlapped. These two sets of DEGs were enriched in distinct biological processes and pathways. There were 268 DEGs between the blue and green groups, which were primarily enriched in the extracellular matrix, and metabolism, receptor activity, and ion binding processes. In addition, nine human genes, including ECEL1, CHRND, SHBG, PRSS56, OVOL1, RDH5, WNT7B, PEBP4, CA12, were identified to be related to myopia development and wavelength response, indicating the potential role of these genes in human wavelength-induced myopia. Conclusions In this study, we identified retinal targets and pathways involved in the response to wavelength signals in emmetropization.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents

BackgroundVision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and...

Effects of screen-based retinal light stimulation measured with a novel contrast sensitivity test.

Myopia is increasing worldwide hence it exists a pressing demand to find effective myopia control strategies. Previous studies have shown that light, spectral composition, spatial frequencies, and contrasts play a critical role in refractive development. The effects of light on multiple retinal processes include growth regulation, but also visual performance and perception. Changes in subjective visual performance can be examined by contrast sensitivity (CS). This study was conducted to investigate whether retinal light stimulation of different wavelength ranges is able to elicit changes in CS and, therefore, may be used for myopia control purposes. In total, 30 right eyes were stimulated with the light of different wavelength ranges, including dominant wavelengths of ∼480 nm, ∼530 nm, ∼630 nm and polychromatic light via a commercial liquid crystal display (LCD) screen. Stimulation was performed screen full-field and on the optic nerve head only. CS was measured before any stimulation and after each stimulation condition using a novel and time-efficient CS test. Post-stimulation CS changes were analyzed by ANOVA regarding the influencing factors spatial frequency, stimulation wavelength and stimulation location. A priorly conducted verification study on a subset of five participants compared the newly developed CS test to a validated CS test. The novel CS test exhibited good reliability of 0.94 logCS and repeatability of 0.13 logCS with a duration of 92 sec ± 17 sec. No clinically critical change between pre- and post-stimulation CS was detected (all p>0.05). However, the results showed that post-stimulation CS differed significantly at 18 cpd after stimulation with polychromatic light from short-wavelength light (p<0.0001). Location of illumination (screen full-field vs. optic nerve head) or any interactions with other factors did not reveal significant influences (all p>0.05). To summarize, a novel CS test measures the relationship between retinal light stimulation and CS. However, using retinal illumination via LCD screens to increase CS is inconclusive.

Significant Axial Elongation with Minimal Change in Refraction in 3- to 6-Year-Old Chinese Preschoolers: The Shenzhen Kindergarten Eye Study

To document the distribution of ocular biometry and to evaluate its associations with refraction in a group of Chinese preschoolers. Population-based cross-sectional study. A total of 1133 preschoolers 3 to 6 years of age from 8 representative kindergartens. Biometric measurements including axial length (AL), anterior chamber depth (ACD), and corneal radius of curvature (CR) were obtained from partial-coherence laser interferometry (IOL Master; Carl Zeiss Meditec, Oberkochen, Germany) before cycloplegia. Lens power (LP) and AL-to-CR ratio were calculated. Cycloplegic refraction (3 drops of 1% cyclopentolate) was measured using an autorefractor (KR8800; Topcon Corp., Tokyo, Japan), and spherical equivalent refraction (SER) was calculated. Biometric and refractive parameters were assessed as a function of age and gender. Multiple regression analysis was performed to explore the associations between refraction and ocular biometry. Ocular biometric distributions and their relationships to refraction. Among the 1127 children (99.5%) with successful cycloplegic refraction, mean SER was 1.37±0.63 diopters (D). Prevalence of myopia increased from 0% at 3 years of age to 3.7% (95% confidence interval, 1.0%-6.5%) at 6 years of age. Biometric parameters followed Gaussian distributions with means of 22.39±0.68 mm for AL, 7.79±0.25 mm for CR, and 24.61±1.42 D for calculated LP; and non-Gaussian distributions with means of 3.34±0.24 mm for ACD and 2.88±0.06 for AL-to-CR ratio. Axial length, ACD, and AL-to-CR ratio increased from 3 to 6 years of age, CR remained stable, whereas LP declined. Overall, SER declined slightly. For the SER variance, AL explained 18.6% and AL-to-CR ratio explained 39.8%, whereas AL, CR, and LP accounted for 80.0% after adjusting for age and gender. Young Chinese children are predominantly mildly hyperopic, with a low prevalence of myopia by the age of 6 years. An increase of 1 mm in AL was associated with only 0.45 D of myopic change. Decreases in LP reduce the myopic shifts that normally would be associated with increases in AL, and thus play a key role in refractive development in this age group.

Pharmacology of myopia and potential role for intrinsic retinal circadian rhythms

Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetylcholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine's role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors.

Image Defocus and Altered Retinal Gene Expression in Chick: Clues to the Pathogenesis of Ametropia

Because of the retina's role in refractive development, this study was conducted to analyze the retinal transcriptome in chicks wearing a spectacle lens, a well-established means of inducing refractive errors, to identify gene expression alterations and to develop novel mechanistic hypotheses about refractive development. One-week-old white Leghorn chicks wore a unilateral spectacle lens of +15 or -15 D for 6 hours or 3 days. With total RNA from the retina/(retinal pigment epithelium, RPE), chicken gene microarrays were used to compare gene expression levels between lens-wearing and contralateral control eyes (n = 6 chicks for each condition). Normalized microarray signal intensities were evaluated by analysis of variance, using a false discovery rate of <10% as the statistical criterion. Selected differentially expressed genes were validated by qPCR. Very few retina/RPE transcripts were differentially expressed after plus lens wear. In contrast, approximately 1300 transcripts were differentially expressed under each of the minus lens conditions, with minimal overlap. For each condition, low fold-changes typified the altered transcriptome. Differentially regulated genes under the minus lens conditions included many potentially informative signaling molecules and genes whose protein products have roles in intrinsic retinal circadian rhythms. Plus or minus lens wear induce markedly different, not opposite, alterations in retina/RPE gene expression. The initial retinal responses to defocus are quite different from those when the eye growth patterns are well established, suggesting that different mechanisms govern the initiation and persistence or progression of refractive errors. The gene lists identify promising signaling candidates and regulatory pathways for future study, including a potential role for circadian rhythms in refractive development.

Accommodative response to peripheral stimuli in myopes and emmetropes

It has been suggested that peripheral refractive error may influence eye growth and the development of axial refractive error, implying that the peripheral retina is sensitive to defocus. This study aimed to evaluate the steady-state accommodative response to peripheral stimuli in 10 young, adult myopes (mean spherical equivalent error -2.10 ± 1.72 D, median -1.63 D, range -0.83 to -6.00 D) and 10 emmetropes (mean spherical equivalent error -0.02 ± 0.35 D, median +0.08 D, range -0.50 to +0.50 D). The subjects were asked to view monocularly the centre of a screen displaying each of a series of eccentric accommodative targets placed at 5, 10 and 15°. An axial target was viewed for comparison purposes. Accommodation was measured using an open-field autorefractor, each stimulus being varied between about 0 and 4 D with spherical trial lenses placed in front of the viewing eye. The results confirm that the peripheral retina is sensitive to optical focus, up to field angles of at least 15°, with accommodative responses weakening as the peripheral angle increases. There is some evidence that peripheral accommodation may be less effective in myopes than emmetropes. Although peripheral accommodation can be demonstrated in the absence of a central stimulus, the accommodation response is normally dominated by the central stimulus and it seems unlikely that peripheral accommodation effects play an important role in refractive development.

Genomewide linkage scans for ocular refraction and meta-analysis of four populations in the Myopia Family Study.

Genomewide linkage scans were performed in Caucasian (CAUC) and Old Order Amish (OOA) families to identify genomic regions containing genes responsible for refractive error control. We also performed a meta-analysis by combining these results with our previous linkage results from Ashkenazi Jewish (ASHK) and African American (AFRAM) families. Two hundred seventy-one CAUC and 411 OOA participants (36 and 61 families, respectively) were recruited to participate in the Myopia Family Study. Recruitment criteria were designed to enrich the sample for multiplex myopic families. Genomewide, model-free, multipoint linkage analyses were performed separately for each population by using >370 microsatellite markers. Empirical significance levels were determined via gene-dropping simulations. A meta-analysis was performed by combining linkage results from the CAUC, OOA, AFRAM, and ASHK samples, and results were compared to previously reported loci for myopia and refraction. Suggestive evidence of linkage was found at 12q24 (LOD = 4.583, P = 0.00037) and 4q21 (LOD = 2.72, P = 0.0028) in the CAUC sample and at 5qter (LOD = 3.271, P = 0.0014) in the OOA. Meta-analysis linkage results were largely driven by population-specific signals from ASHK and AFRAM families. The meta-analysis showed suggestive evidence of linkage to 4q21-22 (meta-P = 0.00214) adjacent to the previously reported MYP9 and MYP11 loci. The results showed suggestive evidence of linkage of ocular refraction to 12q24 and 4q21 in CAUC and to 5qter in OOA families. The meta-analysis supports the view that several genes play a role in refractive development across populations. In MFS families, four broad genomic regions (on 1p, 4q, 7p, and 12q) most likely contain genes that influence ocular refraction.