For example, the effect associated with having a myopic parent for children in quantile 0.05 vs. 0.50 was as follows ALSPAC age 15, -1.19 D (95% CI -1.75 to -0.63) vs. -0.13 D (-0.19 to -0.06), P = 0.001; Generation R age 9, -1.31 D (-1.80 to -0.82) vs. -0.19 D (-0.26 to -0.11), P less then 0.001. Effect sizes for OLS regression were intermediate to those for quantiles 0.05 and 0.50. Conclusions Risk factors for myopia were associated with much larger effects in children in the extremes of the refractive error distribution, providing indirect evidence that emmetropization buffers against both genetic and environmental risk factors.Purpose Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of the translaminar pressure (TLP), which directly effects the optic nerve head. This study measured the diurnal cycle of TLP using continuous wireless telemetry in nonhuman primates (NHPs), a common animal model of glaucoma. Methods We have developed an implantable wireless telemetry system based on a small piezoelectric pressure transducer with low drift. Unilateral IOP was measured in the anterior chamber of the eye, and intracranial pressure (ICP, a surrogate measure of CSFP) was measured in the brain parenchyma in four awake, behaving NHPs for periods of 22 to 281 days. IOP and ICP telemetry transducers were calibrated with direct pressure measurements in the eye (every 2 weeks) and brain (monthly). TLP was quantified in real time as IOP-ICP, and hourly means of IOP, ICP, and TLP were analyzed. Results Results show that mean ICP is significantly higher by an average of 4.8 ± 0.8 mmHg during sleeping hours in NHPs (P less then 0.01). IOP showed a small but significant nocturnal elevation in two of four animals despite NHPs sleeping upright (P less then 0.05). TLP was significantly lower during sleep (7.1 ± 0.6 mmHg; P less then 0.01) than when the animals were awake and active (11.0 ± 0.9 mmHg), driven primarily by the large increase in ICP during sleep. Conclusions The 56% increase in TLP during waking hours in NHPs matches the increase in TLP due to postural change from supine to upright reported previously in humans.Purpose Choroideremia is an inherited retinal degeneration caused by 280 different pathogenic variants in the CHM gene. Only one silent/synonymous variant (c.1359C>T; p.(Ser453=)) has been reported and was classified as inconclusive based on in silico analysis. This study elucidates the pathogenicity of this variant also found in a Brazilian patient. Methods Ophthalmological examinations such as color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and macular integrity assessment microperimetry were performed. The subjects' total RNA was extracted from peripheral blood cells. cDNA was synthesized and the amplification between exon 10 and 14 of the CHM mRNA was performed. The amplification products were sequenced by Sanger sequencing and the results were aligned to the reference sequence. Results The synonymous variant c.1359C>T p.(Ser453=) in the CHM gene is associated with an error in mRNA processing, leading preferentially to production of an aberrant transcript without exon 11 (p.(Gln451Phefs*3)). This anomalous mRNA production is related to typical choroideremia phenotype. Conclusions These molecular findings reinforce the need for more detailed investigation of silent variants in patients with well-defined phenotype of retinal dystrophies. Molecular and clinical findings provided evidence that c.1359C>T (p.(Gln451Phefs*3)) in CHM should be considered a disease-causing variant.Purpose To determine the relationship between funduscopic findings in myopic eyes and the prevalence and structure of the conus in the optical coherence tomographic (OCT) images. Methods A prospective observational cross-sectional study of 121 right eyes of 121 young healthy volunteers. All participants underwent color fundus photography (CFP), scanning laser ophthalmoscopy, and OCT. Based on the OCT analyses, the area between the edge of the ellipsoid zone (EZ) and that of choroid was defined as the "choroidal conus (CC)", and the area between the edge of the choroid and the scleral edge as the "scleral conus (SC)". The eyes were classified into three groups such as the non-conus (NC) group, CC group, and SC group. The differences in the axial length, optic disc tilt, ovality ratio, papillomacular position angle, and peripapillary nerve fiber elevation (pNFE) between the three groups were determined. Results CFPs detected a conus in 79 eyes (65.3 %). The outer border of the conus in CFPs corresponded with the edge of the EZ in the OCT in all subjects. Thirty-seven eyes had CC alone (CC group) and 42 eyes had both CC and SC (SC group). The CC and SC groups had longer axial lengths and more frequent pNFEs than the NC group. There was a significant difference in the optic disc tilt and ovality ratio between the CC and SC groups. Conclusions The eyes with SC tend to have larger optic disc tilt and smaller ovality ratio than the eyes with CC only.Purpose Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR. Methods Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked.  https://www.selleckchem.com/products/bromoenol-lactone.html  Results Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf.