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Background This study aimed to examine changes to optic disc characteristics and macular choroidal microvasculature, and their relationships in young patients with high myopia (HM). Methods: A total of 90 patients were enrolled in this cross‐sectional study. Based on their refractive power, the patients were divided into three groups: 27 in the control group, 34 in the HM group and 29 in the extremely high myopia group. Images of each patient's macula and optic disc were taken by ocular coherence tomography angiography. The macular choroidal and retinal thickness, capillary vessel density and capillary flow area were measured using Matlab software. Parapapillary atrophy (PPA) and the ovality index (OI) obtained from the scanning laser ophthalmoscopy images and the degree of optic disc tilt obtained from the optic nerve head ocular coherence tomography B‐scans were analysed by Image J and Matlab software. Results: The PPA area, OI and degree of optic disc tilt were significantly different among the three groups (all p ≤ 0.001). The macular choroidal thickness and microvasculature were significantly different among the three groups (all p < 0.05). Macular choroidal thickness was significantly correlated with PPA area and the degree of optic disc tilt (r = −0.331, p = 0.003; r = −0.394, p = 0.001, respectively). Macular choroidal capillary vessel density and choriocapillaris flow area were associated with PPA area (r = −0.251, p = 0.047; r = −0.326, p = 0.009, respectively). Conclusions: PPA area, OI and the degree of optic disc tilt were increased in patients with HM, and these changes were correlated with macular choroidal thickness and choroidal microvasculature. [ABSTRACT FROM AUTHOR]

High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three newly identified -genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) in FKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a newly identified European ancestry-specific rare variant in FOLH1. Functional experiments revealed a mechanism whereby a single G-to-A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter of FKBP5 , resulting in decreased transcription of FKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport. [Display omitted] • Large-scale WES of HM identifies an East-Asian-specific risk variant rs533280354 in FKBP5 • rs533280354 disrupts the binding of KLF15 to FKBP5 and decreases its expression • Burden analysis shows SRPK1 and CHRNA3 associated with HM in Han Chinese population • Rare variants in retinal vascular and neurotransmitter-related pathways are enriched in HM Su et al. report a large-scale whole-exome sequencing study of high myopia (HM). They find several ancestry-specific risk variants and candidate genes associated with HM and demonstrate that a low-frequency variant disrupts the binding site of KLF15, resulting in suppressed FKBP5 expression. [ABSTRACT FROM AUTHOR]