The purpose of this study was to study changes in choroidal thickness (ChT) and choroidal blood perfusion (ChBP), and the correlation between them, in guinea pig myopia. METHODS. The reliability of optical coherence tomography angiography (OCTA) for measuring ChT and ChBP was verified in guinea pigs, after cervical dislocation (n ¼ 7) or temporal ciliary artery transection (n ¼ 6). Changes in refraction, axial length, ChT, and ChBP were measured during spontaneous myopia (n ¼ 9), monocular form-deprivation myopia (FDM, n ¼ 13), or lens-induced myopia (LIM, n ¼ 14), and after 4 days of recovery from FDM and LIM. RESULTS. The abolition (by cervical dislocation) or reduction (by temporal ciliary artery transection) of ChBP, and of the associated changes in ChT, were verified by OCTA, thus validating the method of measurement. In the spontaneous myopia group, ChT and ChBP were reduced by 25.2% and 31.9%, respectively. In FDM eyes, mean 6 SD ChT and ChBP decreased significantly compared with the untreated fellow eyes (ChT fellow: 76.13 6 9.34 lm versus 64.76 6 11.15 lm for FDM; ChBP fellow: 37.87 6 6.37 3 10 3 versus 30.27 6 6.06 3 10 3 for FDM) and increased after 4 days of recovery (ChT: 77.94 6 12.57 lm; ChBP: 37.41 6 6.11 3 10 3). Effects of LIM were similar to those of FDM. Interocular differences in ChT and ChBP were significantly correlated in each group (FDM: R ¼ 0.71, P < 0.001; LIM: R ¼ 0.53, P < 0.001). CONCLUSIONS. ChT and ChBP were significantly decreased in all three models of guinea pig myopia, and they both increased during recovery. Changes in ChT were positively correlated with changes in ChBP. Therefore, it is possible that the changes of ChT are responsible for the changes of ChBP or vice versa. Keywords: myopia, choroidal thickness, choroidal blood perfusion, guinea pig M yopia is commonly recognized as an ocular disorder that carries significant risks of visually blinding complications. 1,2 In recent decades, the prevalence and severity of myopia have been on the rise, and it is estimated that by 2050 there will be 4.76 billion people with myopia and 0.94 billion with high myopia. 3-6 Meanwhile, the total cost of myopia correction is also increasing, becoming a relatively large economic burden in urbanized countries. 7-9 With the drastic increase in the public health impact, as well as the socioeconomic burden of myopia, many researchers have focused on investigating the mechanisms underlying myopia development. Twenty years ago, in a seminal study, Wallman et al. found that choroidal thickness (ChT) in chicks significantly increased and decreased in response to positive and negative lens-induced defocus, causing hyperopic and myopic refractive shifts, respectively. 10 On removal of the imposed negative lens defocus, the choroid of the now myopic eye thickened, moving the retina forward toward the defocused image plane. Such bidirectional growth regulation has stimulated researchers to study the choroid as a target tissue for myopia control, and ChT has been investigated as a surrogate marker for...

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10−8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10−3). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.

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