Characterization of Choroidal Morphologic and Vascular Features in Young Men With High Myopia Using Spectral-Domain Optical Coherence Tomography

Gupta, Preeti; Thakku, Sri Gowtham; Saw, Seang‐Mei; Tan, Mellisa; Lim, Edmund Wei Long; Tan, Marcus; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching‐Yu

doi:10.1016/j.ajo.2017.02.001

Cited by 79 publications

(84 citation statements)

References 29 publications

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“…In humans, myopic eyes with higher dioptric values have thinner choroids than those in fellow eyes with lower diopter values (46), and prolonged near work elicits an accommodation process that is associated with myopia development and choroidal thinning (47,48). Choroidal thinning in humans with high myopia is also associated with reductions in both its stromal and vascular components (49). Further, changes in choroidal blood flow precede changes in choroidal thickness subsequent to a recovery period from FD in animal models (50).…”

Section: Hypoxia May Be the Long-sought Myopic Visual Signal Transducmentioning

confidence: 99%

Scleral hypoxia is a target for myopia control

Chen

Zhao

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

268

233

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Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)-signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.

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Section: Hypoxia May Be the Long-sought Myopic Visual Signal Transducmentioning

confidence: 99%

Scleral hypoxia is a target for myopia control

Chen

Zhao

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

268

233

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“…4 Key NHC key Laboratory of Myopia (Fudan University), Shanghai, China. 5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.…”

Section: Availability Of Data and Materialsmentioning

confidence: 99%

“…Despite increased use, the implantation of MfIOLs in myopic cataract eyes remains controversial. In addition to retinal abnormalities [5], the compatibility between IOLs and capsular bag sizes is an issue that cannot be ignored [6,7]. In our previous studies, we found that the compatibility between C-loop haptic IOLs and capsular bag sizes tends to decrease with the elongation of axial length (AXL).…”

Section: Introductionmentioning

confidence: 99%

Decentration and tilt of plate-haptic multifocal intraocular lenses in myopic eyes

Meng

Xiao

et al. 2020

Eye and Vis

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Background: To investigate the decentration and tilt of plate-haptic multifocal intraocular lenses (MfIOLs) in myopic eyes. Methods: Myopic (axial length [AXL] > 24.5 mm) and non-myopic (21.0 mm < AXL ≤ 24.5 mm) cataract eyes were enrolled in this prospective study and randomly assigned to receive implantation of Zeiss AT LISA tri 839MP lenses (Group A) or Tecnis ZMB00 lenses (Group B). In total, 122 eyes of 122 patients were available for analysis. Decentration and tilt of MfIOLs, high-order aberrations (HOAs), and modulation transfer functions (MTFs) were evaluated using the OPD-Scan III aberrometer 3 months postoperatively. Subjective symptoms were assessed with a Quality of Vision questionnaire. Results: Near and distance visual acuities, tilt and horizontal decentration did not differ between the two groups, postoperatively. However, myopic eyes of Group B showed greater vertical decentration than those of Group A (− 0.17 ± 0.14 mm vs.-0.03 ± 0.09 mm, respectively), particularly when the MfIOLs were placed horizontally or obliquely. Overall decentration of myopic eyes was greater in Group B than in Group A (0.41 ± 0.15 mm vs. 0.16 ± 0.10 mm, respectively). In Group B, AXL was negatively correlated with vertical decentration and positively correlated with overall decentration. No such correlations were found in Group A. Intraocular total HOAs, coma, trefoil and spherical aberrations were lower in Group A than in Group B for a 6.0 mm pupil among myopic eyes. Generally, Group A had better MTFs and fewer subjective symptoms than Group B among myopic eyes. Conclusions: Plate-haptic design of MfIOLs may be a suggested option for myopic cataract eyes due to the less inferior decentration and better visual quality postoperatively.

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“…To look deep into the genes with pathogenic variants associated with high myopia, we assembled a list of 709 genes associated with eye diseases (details in variant filtering section of Materials & Methods), including 58 known high myopia genes and 651 ocular disease genes (Table S2). Clinical phenotype related studies have shown that retinal, choroidal and scleral lesions are highfrequency phenotypes in high myopia patients (Brussee et al 2014;Gupta et al 2015;Gupta et al 2017). It would be natural to assume that myopia related genes would be highly expressed in retina and sclera tissues.…”

Section: Resultsmentioning

confidence: 99%

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

2018

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Background. High myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing study to identify potential causal gene mutations. Methods. A total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes. Results. In 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in 5 known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in 7 ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation. Discussion. Systematic mutation analysis of candidate genes was performed using whole exome sequencing (WES) data, functional interaction (FI) network, GO and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.

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Characterization of Choroidal Morphologic and Vascular Features in Young Men With High Myopia Using Spectral-Domain Optical Coherence Tomography

Cited by 79 publications

References 29 publications

Scleral hypoxia is a target for myopia control

Scleral hypoxia is a target for myopia control

Decentration and tilt of plate-haptic multifocal intraocular lenses in myopic eyes

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

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