The Spatial Frequency Content of Urban and Indoor Environments as a Potential Risk Factor for Myopia Development

To examine the hypothesis that the spatial frequency spectra of urban and indoor environments differ from the natural environment in ways that may promote the development of myopia. Methods: A total of 814 images were analyzed from three datasets; University of California Berkeley (UCB), University of Texas (UT), and Botswana (UPenn). Images were processed in Matlab (Mathworks Inc) to map the camera color characteristics to human cone sensitivities. From the photopic luminance images generated, two-dimensional spatial frequency (SF) spectra were calculated and converted to one-dimensional spectra by rotational averaging. The spatial filtering profile of a 0.4 Bangerter foil, which has been shown to induce myopia experimentally, was also determined. Results: The SF slope for natural scenes followed the recognized 1/fα relationship with mean slopes of -1.08, -0.90, and -1.04 for the UCB, UT and UPenn image sets, respectively. Indoor scenes had a significantly steeper slope (-1.48, UCB; -1.52, UT; P \u3c 0.0001). Urban environments showed an intermediate slope (-1.29, UCB; -1.22, UT) that was significantly different from the slopes derived from the natural scenes (P \u3c 0.0001). The change in SF content between natural outdoor scenes and indoors was comparable to that induced by a 0.4 Bangerter foil, which reduced the SF slope of a natural scene from -0.88 to -1.47. Conclusions: Compared to natural outdoor images, man-made outdoor and indoor environments have spatial frequency characteristics similar to those known to induce form-deprivation myopia in animal models. The spatial properties of the man-made environment may be one of the missing drivers of the human myopia epidemic

Diurnal Fluctuations and Developmental Changes in Ocular Dimensions and Optical Aberrations in Young Chicks

PURPOSE. To investigate further the emmetropization process in young chicks by studying the diurnal fluctuations and developmental changes in the ocular dimensions and optical aberrations, including refractive errors, of normal eyes and eyes that had the ciliary nerve sectioned (CNX). METHODS. The ocular dimensions and aberrations in both eyes of eight CNX (surgery on right eyes only) and eight normal chicks were measured with high-frequency A-scan ultrasonography and aberrometry, respectively, four times a day on five different days from posthatching day 13 to 35. A fixed pupil size of 2 mm was used to analyze aberration data. Repeatedmeasures ANOVA was applied to examine the effects of age, time of day, and surgery. RESULTS. Refractive errors and most higher-order aberrations decreased with development in both normal and CNX eyes. However, although normal eyes showed a positive shift in spherical aberration with age, changing from negative spherical aberration initially, CNX eyes consistently exhibited positive spherical aberration. Anterior chamber depth, lens thickness, vitreous chamber depth, and thus optical axial length all increased with development. Many of these ocular parameters also underwent diurnal changes, and mostly these dynamic characteristics showed no age dependency and no effect of CNX. Anterior chamber depth, vitreous chamber depth, and optical axial length were all greater in the evening than in the morning, whereas the choroids were thinner in the evening. Paradoxically, eyes were more hyperopic in the evening, when they were longest. Although CNX eyes, having enlarged pupils, were exposed to larger higher-order aberrations, their growth pattern was similar to that of normal eyes. CONCLUSIONS. Young chicks that are still emmetropizing, show significant diurnal fluctuations in ocular dimensions and some optical aberrations, superimposed on overall increases in the former and developmental decreases in the latter, even when accommodation is prevented. The possibility that these diurnal fluctuations are used to decode the eye's refractive error status for emmetropization warrants investigation. That eyes undergoing ciliary nerve section have more higher-order aberrations but do not become myopic implies a threshold for retinal image degradation below which the emmetropization process is not affected. I t has become increasingly apparent that the eye cannot be viewed as a static system, optically, anatomically, or physiologically. A number of ocular parameters, including refractive errors, ocular dimensions and intraocular pressure (IOP), undergo dynamic changes on both short (seconds) and longer time scales. One interesting manifestation of these dynamics is the various diurnal rhythms that have been reported in conjunction with ocular function. For example, rhythms in melatonin production, IOP, pupil size, and corneal epithelial thickness have been reported. 13,14 The cues used to decode the sign of defocus during emmetropization are not known. Plausibly, the eye could use odd-error cues from astigmatism and higher-order aberrations to decode the sign of defocus (Hunter J, et al. IOVS 2003;44: ARVO E-Abstract 4341). 15 Drawing on an analogy with accommodation in humans where accommodative microfluctuations play a role in decoding the sign of defocus, 16 diurnal fluctuations in refractive errors and/or higher order optical aberrations could play a similar role in emmetropization. Short-term fluctuations in higher-order aberrations 17 as well as changes on the scale of days, weeks, and months have been reported in young adult humans

The significance of retinal image contrast and spatial frequency composition for eye growth modulation in young chicks

AbstractPurpose: This study sought further insight into the stimulus dependence of form deprivation myopia, a common response to retinal image degradation in young animals.Methods: Each of 4 Bangerter diffusing filters (0.6, 0.1, <0.1, and LP (light perception only)) combined with clear plano lenses, as well as plano lenses alone, were fitted monocularly to 4-day-old chicks. Axial ocular dimensions and refractive errors were monitored over a 14-day treatment period, using high frequency A-scan ultrasonography and an autorefractor, respectively.Results: Only the <0.1 and LP filters induced significant form deprivation myopia; these filters induced similarly large myopic shifts in refractive error (mean interocular differences±SEM: −9.92±1.99, −7.26±1.60D, respectively), coupled to significant increases in both vitreous chamber depths and optical axial lengths (p<0.001). The other 3 groups showed comparable, small changes in their ocular dimensions (p>0.05), and only small myopic shifts in refraction (<3.00D). The myopia-inducing filters eliminated mid-and-high spatial frequency information.Conclusions: Our results are consistent with emmetropization being tuned to mid-spatial frequencies. They also imply that form deprivation is not a graded phenomenon

Double-Pass Measurement of Retinal Image Quality in the Chicken Eye

8 pages, 6 figures.-- PMID: 12553544 [PubMed].-- This research was presented as a paper at the annual meeting of the Association for Research in Vision and Ophthalmology on May 4, 2000, in Ft. Lauderdale, FL.[Purpose] The chicken, Gallus gallus domesticus, is used as an animal model to study the development of refractive error. Although vision is important in determining the eye's refractive state, relatively little is known about the retinal image quality of the chicken eye. An objective double-pass technique was used to measure the optical quality of the eyes of White Leghorn chickens.[Methods] Measurements were made on 21 eyes of six untreated birds and eight experimental birds that were members of a study of refractive development. Ages ranged from 3 to 6 weeks, and refractions ranged from -1.29 to +0.58 D in the untreated eyes and -4.58 to +10.17 D in the experimental eyes. The measurements were made under general anesthesia combined with either cycloplegia or ciliary nerve section. Proper optical alignment of the eye was achieved with the aid of a TV monitor, CCD camera, and an infrared source. A 543-nm laser point source was focused on the retina, and the double-pass aerial image was collected by a high-resolution CCD camera. Refractive errors were corrected with trial lenses, using a bracketing method to optimize the retinal images. Both the full width at half-maximum of the double-pass aerial image and the single-pass modulation transfer function were used as objective estimates of the optical quality.[Results] The mean full width at half-maximum value in eyes of the untreated birds was 1.60 min arc for a 4.50-mm mean pupil diameter. Optical quality tended to be worse in the experimental myopic eyes.[Conclusions] The optical quality of the chicken eye measured under monochromatic conditions meets or may even exceed the neural limits of spatial acuity based on anatomical estimates of ganglion cell spacing. The data also suggest that optical quality is worse in myopic eyes, which is consistent with studies of human eyes.Support for this research was provided by National Eye Institute, National Institutes of Health grants EY04395 to S. Burns, EY11228 to D. Troilo, EY12392 to C. Wildsoet, and EY12847 to N. Coletta. S. Marcos was supported by the Human Frontier Science Program LT/0542/1997-B and Fulbright 163/2000.Peer reviewe

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PURPOSE. To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. METHODS. Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. RESULTS. Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469). CONCLUSIONS. Common genetic variants within or nearby genes that cause syndromic myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis of syndromic forms of refractive errors can provide new insights into the etiology of myopia and additional potential targets for therapeutic interventions

Posterior retinal contour in adult human anisomyopia

PURPOSE. It is well documented that myopia is associated with an increase in axial length or, more specifically, in vitreous chamber depth. Whether the transverse dimensions of the eye also increase in myopia is relevant to further understanding of its development. METHODS. The posterior retinal surface was localized in two-dimensional space in both eyes of young adult white and Taiwanese-Chinese iso- and anisomyopes (N = 56), from measured keratometry, A-scan ultrasonography, and central and peripheral refraction (±35°) data, with the aid of a computer modeling program designed for this purpose. Anisomyopes had 2 D or more interocular difference in their refractive errors, with mean values in their more myopic eyes of -5.57 D and in their less myopic eyes of -3.25 D, similar to the means of the two isomyopic groups. The derived retinal contours for the more and less myopic eyes were compared by way of investigating ocular shape changes that accompany myopia, in the posterior region of the vitreous chamber. The presence and size of optic disc crescents were also investigated as an index of retinal stretching in myopia. RESULTS. Relative to the less myopic eyes of anisometropic subjects, the more myopic eyes were more elongated and also distorted into a more prolate shape in both the white and Chinese groups. However, the Chinese eyes showed a greater and more uniform relative expansion of the posterior retinal surface in their more myopic eyes, and this was associated with larger optic disc crescents. The changes in the eyes of whites displayed a nasal-temporal axial asymmetry, reflecting greater enlargement of the nasal retinal sector. CONCLUSIONS. Myopia is associated with increased axial length and a prolate shape. This prolate shape is consistent with the proposed idea that axial and transverse dimensions of the eye are regulated differently. The observations that ocular shape changes are larger but more symmetrical in Chinese eyes than in eyes of whites warrant further investigation

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

P URPOSE . To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors

Biochemistry and Molecular Biology Bidirectional, Optical Sign-Dependent Regulation of BMP2 Gene Expression in Chick Retinal Pigment Epithelium

PURPOSE. We explored the role of bone morphogenic protein 2 (BMP2) in defocus-induced ocular growth using gene expression changes in RPE as a surrogate. METHODS. Young White-Leghorn chickens were used in this study. Normal gene expression of BMP2 and its receptors was examined in retina, RPE, and choroid, and BMP2 protein expression assessed in the same tissues using Western blots and immunohistochemistry. Quantitative PCR (qPCR) was used to assess the effects of short-term exposure (2 or 48 hours) to monocular þ10 and À10 diopter (D) lenses, on RPE gene expression of BMP2 and its receptors. Ocular growth was assessed using A-scan ultrasonography. RESULTS. In the eyes of untreated chickens, BMP2 mRNA was expressed more highly in RPE compared to retina and choroid and all three tissues expressed BMP2 protein. The gene expression for all three receptors also was detected in these tissues, with BMPR2 showing highest and BMPR1B lowest expression. BMP2 was up-regulated in the RPE from eyes wearing þ10 D lenses, which exhibited shorter than normal vitreous chambers (VCDs) and thickened choroids, while BMP2 was down-regulated in the RPE from eyes wearing À10 D lenses, which developed enlarged VCDs. These treatments did not induce differential expression of BMP receptors in RPE. CONCLUSIONS. That mRNA expression of BMP2 in chick RPE shows bidirectional, defocus sign-dependent changes is suggestive of a role for BMP2 in eye growth regulation, although the diffuse ocular expression of BMP2 and its receptors suggests complex growth-modulatory signal pathways. (Invest Ophthalmol Vis Sci. 2012;53:6072-6080

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests