Hyperopia

Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained ("missing heritability"). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5'-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10-4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10-3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10-3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p < 1.0 × 10-4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10-4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10-4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10-4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10-4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the "missing" myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.

Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

BackgroundStudies show great variability in the prevalence of hyperopia among children. This study aimed to synthesize the existing knowledge about hyperopia prevalence and its associated factors in school children and to explore the reasons for this variability.MethodsThis systematic review followed PRISMA guidelines. Searching several international databases, the review included population- or school-based studies assessing hyperopia through cycloplegic autorefraction or cycloplegic retinoscopy. Meta-analysis of hyperopia prevalence was performed following MOOSE guidelines and using the random effects model.ResultsThe review included 40 cross-sectional studies. The prevalence of hyperopia ranged from 8.4% at age six, 2-3% from 9 to 14 years and approximately 1% at 15 years. With regard to associated factors, age has an inverse association with hyperopia. The frequency of hyperopia is higher among White children and those who live in rural areas. There is no consensus about the association between hyperopia and gender, family income and parental schooling.ConclusionFuture studies should use standardized methods to classify hyperopia and sufficient sample size when evaluating age-specific prevalence. Furthermore, it is necessary to deepen the understanding about the interactions among hyperopic refractive error and accommodative and binocular functions as a way of identifying groups of hyperopic children at risk of developing visual, academic and even cognitive function sequelae.

PurposeThe oculomotor system, which controls eye movements, is closely linked to visual processing. While refractive errors are common, their influence on oculomotor behavior remains underexplored. This study compared oculomotor performance among emmetropic, myopic, and hyperopic individuals.MethodsIn this cross-sectional, single-visit study, 67 participants (33 myopes, 10 hyperopes, 24 emmetropes; mean age 25.9 ± 3.0 years) completed fixation and visually guided saccade tasks at a viewing distance of 57 cm. A centrally positioned black, disc-shaped target (0.50° in diameter) was displayed on the screen for 45 seconds, after which it shifted to a predetermined location to elicit visually guided saccades. Clinical measures were included in the correlation analysis to ensure the findings were clinically relevant and to examine relationships between research variables and patient outcomes. Eye movements were recorded using the EyeLink 1000Plus. Fixation stability was quantified using Bivariate Contour Ellipse Area (BCEA). Fixational saccade metrics, vergence stability, and saccadic behavior were analyzed. Axial length and corneal power were measured using a portable ultrasound scanner.ResultsFixation stability differed significantly across groups, with myopes exhibiting larger BCEA values compared to emmetropes (H[2] = 10.6, p ConclusionMyopes exhibited more unstable fixation, characterized by larger, faster, and more frequent fixational saccades. These findings suggest distinct oculomotor behavior in myopia, potentially reflecting altered spatiotemporal processing during visual development.