Role In Development Of Myopia Research Articles

Unveiling the gut microbiota and metabolite profiles in guinea pigs with form deprivation myopia through 16S rRNA gene sequencing and untargeted metabolomics

AimThe aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive intestinal peptide (VIP), lipopolysaccharides (LPS), specific gut microbiota and their metabolites. Method20 specific-pathogen-free (SPF) guinea pigs were divided into the FDM and the control(Con) group. Following model induction, serum levels of VIP and LPS were quantified. A combination of 16S ribosomal ribosomal Ribonucleic Acid (rRNA) gene sequencing, non-targeted metabolomics and bioinformatics analysis were employed to identify disparities in gut microbiota and metabolites between the two groups of guinea pigs. ResultCompared to the control group, FDM guinea pigs exhibited a significant trend towards myopia, along with significantly elevated concentrations of LPS and VIP (p < 0.0001). Furthermore, Ruminococcus_albus emerged as the predominant bacterial community enriched in FDM (p < 0.05), and demonstrated positive correlations with 10 metabolites, including l-Glutamic acid, Additionally, Ruminococcus_albus exhibited positive correlations with VIP and LPS levels (p < 0.05). ConclusionThe findings suggest that the Ruminococcus_Albus and glutamate metabolic pathways play a significant role in myopia development, leading to concurrent alterations in serum VIP and LPS levels in FDM guinea pigs. This underscores the potential of specific gut microbiota and their metabolites as pivotal biomarkers involved in the pathogenesis of myopia.

Assessment of the effects of myopic and hyperopic anisometropia on choroidal vascular structure in children using SS-OCTA.

To compare large- and medium-sized choroidal vascularity and the choriocapillaris (CC) flow area in children with different refractive errors using swept-source optical coherence tomography angiography (SS-OCTA). Forty-two anisometropic children were enrolled and divided into hyperopic anisometropia (HA) and myopic anisometropia (MA) groups. SS-OCTA was performed to analyse choroidal vascularity. Mean choroidal thickness (CT), choroidal vascularity volume (CVV), choroidal vascularity index (CVI) and CC flow area were compared between the two eyes. The inter-ocular differences between the two groups were also determined. Mean CT and CVV were highest in eyes with shorter axial lengths in both refractive groups, and the difference between the two eyes was positively correlated with the difference in axial length at the foveal region. Significant differences in the CVI in the MA group were only found in the parafoveal region. Inter-ocular differences in the CC were significantly reduced in eyes with longer axial lengths in the foveal and parafoveal regions of the HA and MA groups, respectively. Comparing inter-ocular differences, CC was significantly greater in the parafoveal region of the MA group than the HA group. All layers of choroidal vasculature were thinner in eyes with longer axial lengths in all groups. The inter-ocular CC difference was greater in the MA than in the HA group, with similar differences in axial length. This suggests that both medium-to-large choroidal vascular and choroidal capillaries may play a role in myopia development.

Epitranscriptomic investigation of myopia-associated RNA editing in the retina.

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development.

Effects of Morning or Evening Narrow-band Blue Light on the Compensation to Lens-induced Hyperopic Defocus in Chicks.

Exposure to blue light before bedtime is purported to be deleterious to various aspects of human health. In chicks, blue evening light stimulated ocular growth, suggesting a role in myopia development. To further investigate this hypothesis, we asked if brief blue light altered the compensatory responses to hyperopic defocus. Previous work showed that several hours' evening exposure to blue light stimulated ocular growth in chicks, but morning exposure was only effective at a lower illuminance. By contrast, rearing in blue light has inhibited ocular growth in untreated eyes and eyes exposed to form deprivation or defocus. We studied the effects of brief exposures to blue light on the compensation to hyperopic defocus. Chicks wore monocular negative lenses (-10 D) starting at age 10 days. They were subsequently exposed to blue light (460 nm) for 4 hours in the morning or evening for 8 to 9 days ("dim," 200 lux[morning, n = 9; evening, n = 11]; "bright," 600 lux[morning, n = 8; evening, n = 20]); controls wore lenses in white light (n = 14). Ultrasonography was done on days 1, 5, 8, and 9 for "evening" groups and days 1, 6, and 8 for "morning." All data are reported as interocular differences (experimental minus fellow eyes). Refractions were measured on the last day. For evening exposure, dim blue light enhanced the axial compensation at all times (change in axial length: day 6: 465 vs. 329 μm/9 days, analysis of variance P < .001, P = .03; day 9: 603 vs. 416 μm/9 days, analysis of variance P < .001; P < .05). Bright blue light had a transient inhibitory effect (day 5: 160 vs. 329 μm; P < .005). Refractive errors were consistent with axial growth, with dim causing more myopia than bright (-9.4 vs. -4.7 D; P < .05). Morning blue light had no significant effect. We speculate that these findings reflect a complex interaction between illuminance, defocus, and time of day.

Insights into myopia gleaned from retinal electrophysiology

AbstractThe prevalence of myopia is increasing dramatically. Retinal signalling controls eye growth and a retinal myopia‐signalling cascade has been postulated. One of the strongest genetic associations with myopia susceptibility is a locus near the GJD2 gene which codes for a protein forming gap junctions in the retina. We explored whether any parameters of retinal electrophysiology were associated with presence of the risk allele. Full‐field scotopic and photopic electroretinogram (ERG) recording was performed in over 200 healthy volunteers from the TwinsUK cohort. Responses were elicited by stimuli conforming to international standard protocols and additional experimental protocols aimed at isolating rod and cone system responses. The majority of participants had been genotyped previously for their identity at the relevant locus. A mixed linear model was employed with ERG parameters (amplitudes and peak times) as outcomes and allelic dosage at the relevant locus as a predictor, adjusting for age, sex and inter‐individual relatedness. ERG recordings and genotype data were available for the majority of participants (95% female; mean (SD) age 64.2 (9.7) years). Light adapted single‐flash a‐waves and b‐waves associated significantly with allelic identity at the locus of interest. None of the standard dark‐adapted ERG parameters associated significantly with genotype at this locus. Further investigation of responses to experimental protocols, and those obtained from patients with loss of ON or both ON and OFF bipolar cell responses, suggested changes specific to the cone‐driven OFF pathway. The findings suggest associations between photopic cone‐driven retinal electrophysiological signalling and one of the genetic polymorphisms most strongly linked to myopia. Higher environmental light levels are known to be protective in myopia, and our results support the hypothesis that changes in light‐adapted cone system signalling might play a role in myopia development.

Studies on the interactions of retinal dopamine with choroidal thickness in the chicken

PurposeRecently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken.MethodsChanges in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence.ResultsThe choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone–injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor–positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF.ConclusionsRetinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.

MicroRNA-29a May Influence Myopia Development by Regulating Collagen I

ABSTRACTPurposeThe aim of this study was to characterize the regulatory role of microRNA-29a (miR-29a) in myopia, providing support for potential biomarkers and new therapeutic targets of myopia in humans.MethodsThe miR-29a expression level was detected in the aqueous humor and peripheral blood plasma of 21 high myopic patients and eight cataract control patients using quantitative polymerase chain reaction. iTRAQ analysis of proteomes was conducted to show the regulatory effect of miR-29a on human scleral fibroblasts (SFs) cultured in vitro. We also assessed proliferation, migration, and collagen I synthesis in SF cells, mediated by miR-29a.ResultsMiR-29a expression was significantly higher in the aqueous humor of highly myopic patients than in the cataract control patients (fold change: 4.861, p = 0.001). miR-29a inhibited the synthesis of type I collagen in human SF cells and enhanced cell migration, but had no significant effect on cell proliferation.ConclusionMiR-29a was highly expressed in aqueous humor of myopia patients and inhibited the synthesis of type I collagen in human SF cells in vivo, thereby it may play an important role in myopia development.

Studies on retinal mechanisms possibly related to myopia inhibition by atropine in the chicken.

While low-dose atropine eye drops are currently widely used to inhibit myopia development in children, the underlying mechanisms are poorly understood. Therefore, we studied possible retinal mechanisms and receptors that are potentially involved in myopia inhibition by atropine. A total of 250μg atropine were intravitreally injected into one eye of 19 chickens, while the fellow eyes received saline and served as controls. After 1h, 1.5h, 2h, 3h, and 4h, eyes were prepared for vitreal dopamine (DA) measurements, using high-pressure liquid chromatography with electrochemical detection. Twenty-four animals were kept either in bright light (8500lx) or standard light (500lx) after atropine injection for 1.5h before DA was measured. In 10 chickens, the α2A-adrenoreceptor (α2A-ADR) agonists brimonidine and clonidine were intravitreally injected into one eye, the fellow eye served as control, and vitreal DA content was measured after 1.5h. In 6 chickens, immunohistochemical analyses were performed 1.5h after atropine injection. Vitreal DA levels increased after a single intravitreal atropine injection, with a peak difference between both eyes after 1.97h. DA was also enhanced in fellow eyes, suggesting a systemic action of intravitreally administered atropine. Bright light and atropine (which both inhibit myopia) had additive effects on DA release. Quantitative immunolabelling showed that atropine heavily stimulated retinal activity markers ZENK and c-Fos in cells of the inner nuclear layer. Since atropine was recently found to also bind to α2A-ADRs at doses where it can inhibit myopia, their retinal localization was studied. In amacrine cells, α2A-ADRs were colocalized with tyrosine hydroxylase (TH), glucagon, and nitric oxide synthase, peptides known to play a role in myopia development in chickens. Intravitreal atropine injection reduced the number of neurons that were double-labelled for TH and α2A-ADR. α2A-ADR agonists clonidine and brimonidine (which were also found by other authors to inhibit myopia) severely reduced vitreal DA content in both injected and fellow eyes, compared to eyes of untreated chicks. Merging our results with published data, it can be concluded that both muscarinic and α2A-adrenergic receptors are expressed on dopaminergic neurons and both atropine and α2A-ADR antagonists stimulate DA release whereas α2A-ADR agonists strongly suppress its release. Stimulation of DA by atropine was enhanced by bright light. Results are in line with the hypothesis that inhibition of deprivation myopia is correlated with DA stimulation, as long as no toxicity is involved.

Role of microfluctuations in accommodation: a novel approach to reduce non-accommodative noise.

Accommodative response and its possible role in myopia development has been explored through the study of the microfluctuations (MFs) of accommodation, which are commonly divided in high (1.0 to 2.3 Hz) and low (0.1 to 0.6 Hz) frequency components. Previous research efforts have evidenced that a certain percentage of the amplitude of MFs seems not to originate in the accommodative response. We aimed to develop and test a new approach to reduce this non-accommodative noise. For this purpose, ten healthy participants were enrolled to determine the difference between the amplitude of MFs at near and distance for each range of frequencies, which was defined as the relative amplitude of MFs. The findings support the exploration of the relative rather than absolute values of the amplitude of MFs to better understand the contribution of both accommodative and non-accommodative factors to MFs.

Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia

Myopia, commonly referred to as nearsightedness, is one of the most common causes of visual disability throughout the world. It affects more people worldwide than any other chronic visual impairment condition. Although the prevalence varies among various ethnic groups, the incidence of myopia is increasing in all populations across globe. Thus, it is considered a pressing public health problem. Both genetics and environment play a role in development of myopia. To elucidate the epigenetic mechanism(s) underlying the pathophysiology of high-myopia, we conducted methylation profiling in 18 cases and 18 matched controls (aged 4–12 years), using Illumina MethylationEPIC BeadChips array. The degree of myopia was variable among subjects, ranging from −6 to −15D. We identified 1541 hypermethylated CpGs, representing 1745 genes (2.0-fold or higher) (false discovery rate (FDR) p ≤ 0.05), multiple CpGs were p < 5 × 10−8 with a receiver operating characteristic area under the curve (ROC-AUC) ≥ 0.75 in high-myopia subjects compared to controls. Among these, 48 CpGs had excellent correlation (AUC ≥ 0.90). Herein, we present the first genome-wide DNA methylation analysis in a unique high-myopia cohort, showing extensive and discrete methylation changes relative to controls. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination.

Patterns of Daily Outdoor Light Exposure in Australian and Singaporean Children.

PurposeMyopia is rising in prevalence in many locations, and there is evidence that outdoor light exposure is a major environmental factor playing a role in myopia development. This study examined the patterns of daily light exposure in similarly aged children from two geographic locations (Australia and Singapore) known to exhibit differences in myopia prevalence.MethodsWearable light sensors were used to assess daily light exposure in 69 Singaporean children aged 8 to 12 years (mean, 9.2 ± 1.1) and 43 Australian children aged 10 to 12 years (mean, 11.3 ± 0.6). The mean daily time exposed to bright outdoor light (>1000 lux) and the number and duration of daily episodes of outdoor exposure were examined.ResultsPatterns of daily outdoor light exposure differed substantially between Australia and Singapore. Australian children (105 ± 42 min/d) experienced significantly longer daily outdoor light exposure than Singaporean children (61 ± 40 min/d; P = 0.005), with the largest differences found on weekdays during school hours. Australian children (6.9 ± 1.5 episodes per day) had more frequent daily episodes of outdoor light exposure compared with Singaporean children (4.6 ± 1.5; P = 0.02); however, there was no significant difference in the mean duration of these episodes between countries (P = 0.54).ConclusionsChildren living in Singapore were exposed to significantly less daily outdoor light than Australian children, and these differences may be one of several factors contributing to the differences in myopia prevalence typically found between these populations.Translational RelevanceKnowledge of these light exposure patterns may assist in the design of outdoor interventions, including school programs, to increase outdoor time in urban Asian populations.

Differences in retinal shape between East Asian and Caucasian eyes.

To investigate whether retinal shape is different between East Asians and Caucasians. There were 36 East Asian and 40 Caucasian young adults, with refractions between +0.75D and -5.50D. Peripheral eye lengths were obtained after pupil dilation using the Lenstar partial coherence interferometer. Measurements were obtained along the horizontal and vertical meridians of the visual field out to ±35° and ±30°, respectively, in 5° steps. Retinal co-ordinates were estimated using a validated method from the peripheral eye length measurements and ray-tracing through a modified Le Grand full theoretical eye. Rays were directed normally towards the anterior cornea. Retinal shapes were described in terms of vertex radius of curvature (Rv ), asphericity (Q) and equivalent radius of curvature (REq ) along both horizontal and vertical meridians. Rv was smaller in East Asian than in Caucasians (mean difference ± 95% CI -0.7 ± 0.5 mm), along the horizontal meridian than the vertical meridian (-1.2 ± 0.6 mm), and in myopia than in emmetropia (-1.0 ± 0.6 mm). Rv along the horizontal meridian, but not along the vertical meridian, became smaller as myopia increased. Q did not vary significantly with meridian, refraction group or race. The same pattern of results occurred for REq as for Rv . The percentage differences of heights under the estimated retinal surfaces showed steeper retinas in East Asians than in Caucasians; the differences between East Asian and Caucasian emmetropes were 2.5% and <1% along horizontal and vertical meridians, respectively, and corresponding differences for myopes were 4.6% and 1.8%. East Asians had steeper retinas than Caucasians. The horizontal meridian had steeper retinas than the vertical meridian. Myopes had steeper retinas than emmetropes. Racial differences in retinal shape in both emmetropes and myopes, combined with the high prevalence of myopia in East Asia, suggest that retinal shape may play a role in myopia development.

Time outdoors, blood vitamin D status and myopia: a review.

Myopia is a major public health concern throughout the world and the prevalence has been increasing rapidly in recent years, especially in urban Asia. The "vitamin D hypothesis" has been raised recently because vitamin D may be a link between less time outdoors and increased risk of myopia. We reviewed all studies published in English which examined the association of time outdoors and blood vitamin D status with myopia. The protective effect of time spent outdoors on the risk of myopia onset has been well-established with numerous observational studies and three trials published. Five studies reporting the association between the blood vitamin D status and the risk of myopia and two studies examining the variations in the vitamin D receptor as potential risk factors for myopia development were identified. Most of the current evidence was cross-sectional in nature and had not properly controlled important confounders in its analyses. The evidence supporting that vitamin D played a role in myopia development is weak and the mechanisms are unclear. At the current stage, it is still unclear whether blood vitamin D status regulates the onset or progression of myopia. Blood vitamin D status may only serve as a biomarker of outdoor exposure, which is the real protective factor for myopia.

Altered TGF-β2 and bFGF expression in scleral desmocytes from an experimentally-induced myopia guinea pig model

To determine changes in expression of transforming growth factor β-2 (TGF-β2) and basic fibroblast growth factor (bFGF) in scleral desmocytes from anterior and posterior portions of experimentally-induced myopic eyes of guinea pigs. Three groups (n = 10) of 2-week-old guinea pigs were used to develop concave lens-induced myopia (LIM) in one eye via the out-of-focus method for 6, 15, or 30 days respectively, while the other eye in each guinea pig served as the self-control (SC). After myopia induction, lenses were removed, and scleral fibroblasts were cultured and passaged twice. TGF-β2 and bFGF expression levels of scleral desmocytes in LIM and SC groups were compared by immunocytochemistry, quantitative real-time PCR (qRT-PCR) and Western blot analyses. The TGF-β2 expression of the anterior portion of the sclera in the LIM group was significantly higher at 15 days, and at its highest at 30 days after myopia induction compared with the SC group (P < 0.05). The TGF-β2 staining of the posterior sclera in the LIM group began to rise significantly at 6 days, peaked at 15 days and remained significantly higher than that of the anterior part, as well as the SC group, even at 30 days after myopia induction (P < 0.05). BFGF levels in scleral desmocytes from the anterior and posterior regions in the LIM group were both significantly lower than those of the SC group at all time points after myopia induction (P < 0.05). Furthermore, as the myopia progressed, bFGF expression in the anterior and posterior sclera in the LIM group gradually and statistically significantly decreased compared with the SC group (P < 0.05); however, no significant differences were observed between the anterior and posterior parts in the LIM group at any time after myopia induction (P > 0.05). All these results were consistent at the mRNA and protein levels. During myopia development in lens-induced guinea pigs, the increase in TGF-β2 activity of scleral desmocytes initiated at the posterior pole. Along with the induction time, the TGF-β2 activity in all scleral desmocytes became elevated. By contrast, the bFGF activity showed a general decline in all scleral desmocytes, rather than mainly in the posterior pole. These results imply that expression of TGF-β2 in scleral desmocytes plays a direct role, while that of bFGF exerts an indirect role in myopia development.

Worldwide prevalence and risk factors for myopia

Myopia, the most common type of refractive error, is a complex trait including both genetic and environmental factors. Numerous studies have tried to elucidate the aetiology of myopia. However, the exact aetiology of myopia is still unclear. To summarize the worldwide patterns and trends for the prevalence of myopia and to evaluate the risk factors for myopia in population-based studies. The prevalences of myopia vary across populations of different regions and ethnicities. In population-based studies on children, the prevalence of myopia has been reported to be higher in urban areas and Chinese ethnicity. The regional and racial difference is not so obvious in adult populations aged over 40 years. More time spent on near work, less time outdoors, higher educational level and parental history of myopia have been reported to increase the risk of myopia. Environmental factors play a crucial role in myopia development. The effect of gene-environment interaction on the aetiology of myopia is still controversial with inconsistent findings in different studies. A relatively hyperopic periphery can stimulate compensating eye growth in the centre. Longitudinal cohort studies or randomized clinical trials of community-based health behaviour interventions should be conducted to further clarify the aetiology of myopia.

Effect of accommodation on peripheral ocular aberrations

Changes in peripheral aberrations, particularly higher order aberrations, as a function of accommodation have received little attention. Wavefront aberrations were measured for the right eyes of 9 young adult emmetropes at 38 field positions in the central 42 x 32 degrees of the visual field. Subjects accommodated monocularly to targets at vergences of either 0.3 or 4.0 D. Wavefront data for a 5-mm diameter pupil were analyzed either in terms of the vector components of refraction or Zernike coefficients and total RMS wavefront aberrations. Relative peripheral refractive error (RPRE) was myopic at both accommodation demands and showed only a slight, not statistically significant, hypermetropic shift in the vertical meridian with the higher accommodation demand. There was little change in the astigmatic components of refraction or the higher order Zernike coefficients, apart from fourth-order spherical aberration, which became more negative (by 0.10 microm) at all field locations. Although it has been suggested that nearwork and the state of peripheral refraction may play some role in myopia development, for most of our adult emmetropes any changes with accommodation in RPRE and aberration were small. Hence it seems unlikely that such changes can be of importance to late-onset myopization.

Corneal Optics after Reading, Microscopy and Computer Work

To compare lid-induced changes in corneal optics following reading, microscopy and computer work. Nine subjects with normal ocular health were recruited for the study. Five subjects were myopic, two were emmetropic, one was astigmatic and one was hyperopic. Corneal topography was measured before and after 60 mins of reading a novel, performing a blood cell counting task on a microscope and Internet searching. Corneal topography data were used to derive the corneal wavefront Zernike coefficients up to the fourth order. A meridian analysis of instantaneous corneal power along the upper 90-degree semi-meridian was performed to examine local changes caused by eyelid pressure. Digital photography was used to capture body posture and eyelid position during the tasks. Each of the three tasks showed systematically different effects on both the characteristics and location of corneal topography changes. Reading and microscopy generally exhibited larger and more centrally located changes compared with the computer task. Differences in wavefront aberration characteristics between the three tasks were apparent in both lower and higher order aberrations. The location of corneal distortions differed significantly between microscopy and computer work, with microscopy causing distortions to occur closer to the videokeratoscope measurement axis compared with computer work (p = 0.015). Reading, microscopy and computer work have different effects on corneal aberrations. The results are in agreement with the hypothesis that lid-induced corneal aberrations may play a role in myopia development.

Aberrations and myopia

It has been suggested that high levels of axial aberration or specific patterns of peripheral refraction could play a role in myopia development. Possible mechanisms involving high levels of retinal image blur caused by axial aberrations include form deprivation through poor retinal image quality in distance vision, enhanced accommodative lags favouring compensatory eye growth, and an absence of adequate directional cues to guide emmetropization. In addition, in initially emmetropic eyes, hyperopia in the retinal periphery may result in local compensatory eye growth, which induces axial myopia. Evidence in support of these ideas is reviewed and it is concluded that, for any fixed pupil diameter, evidence for higher levels of axial aberration in myopes in comparison with other refractive groups is weak, making involvement of axial aberrations in myopization through image degradation at the fovea unlikely. If, however, some potential myopes had unusually large pupil diameters, their effective aberration levels and associated retinal blur would be larger than those of the rest of the population. There is stronger evidence in favour of differences in patterns of peripheral refraction in both potential and existing myopes, with myopes tending to show relative hyperopia in the periphery. These differences appear to be related to a more prolate eyeball shape. Longitudinal studies are required to confirm whether the retinal defocus associated with the peripheral hyperopia can cause patterns of eyeball growth which lead to axial myopia.

A Susceptibility Locus for Myopia in the Normal Population Is Linked to the PAX6 Gene Region on Chromosome 11: A Genomewide Scan of Dizygotic Twins

Myopia is a common, complex trait with considerable economic and social impact and, in highly affected individuals, ocular morbidity. We performed a classic twin study of 506 unselected twin pairs and inferred the heritability of refractive error to be 0.89 (95% confidence interval 0.86-0.91). A genomewide scan of 221 dizygotic twin pairs, analyzed by use of optimal Haseman-Elston regression methods implemented by use of generalized linear modeling, showed significant linkage (LOD >3.2) to refractive error at four loci, with a maximum LOD score of 6.1 at 40 cM on chromome 11p13. Evidence of linkage at this locus, as well as at the other linkage peaks at chromosomes 3q26 (LOD 3.7), 8p23 (LOD 4.1), and 4q12 (LOD 3.3), remained the same or became stronger after model fit was checked and outliers were downweighted. Examination of potential candidate genes showed the PAX6 gene directly below the highest peak at the 11p13 locus. PAX6 is fundamental to identity and growth of the eye, but reported mutations usually result in catastrophic congenital phenotypes such as aniridia. Haplotype tagging of 17 single-nucleotide polymorphisms (SNPs), which covered the PAX6 gene and had common minor allele frequencies, identified 5 SNPs that explained 0.999 of the haplotype diversity. Linkage and association analysis of the tagging SNPs showed strong evidence of linkage for all markers with a minimum chi 21 of 7.5 (P=.006) but no association. This suggests that PAX6 may play a role in myopia development, possibly because of genetic variation in an upstream promoter or regulator, although no definite association between PAX6 common variants and myopia was demonstrated in this study.

Low‐grade myopia in children with regressed retinopathy of prematurity

Myopia is a frequent sequelae of retinopathy of prematurity. The mechanism for myopia development in children born preterm is not well understood. From a group of 33 myopic preterm children we selected those who had regressed retinopathy and myopic values < or = 5 D. Seventeen children met our criteria. Of them, 10 patients could be re-examined. Factors related to myopia development were analyzed and compared to a control group of 12 children born fullterm with emmetropia or low hypermetropia, as well as another group of 10 fullterm children with myopic values < or = 5 D. The age of children ranged from 9 to 14 years in all groups. The mean birth weight in myopic premature children was 1249.3 g. Higher keratometric diopter values were found in myopic premature children than in emmetropic fullterm children (p < 0.05) and myopic fullterm children (p < 0.05). Increased axial length values were observed in myopic fullterm children when compared to myopic premature children (p < 0.05) In children born preterm the corneal refractive power seems to play a major role in myopia development.