Purpose <p>To evaluate the posterior scleral stiffness of different regions in high myopic eyes and to explore its associations with macular choroidal and peripapillary retinal nerve fiber layer (pRNFL) thickness and vasculature.</p> Methods <p>Thirty subjects with high myopic eyes and 30 subjects with low myopic eyes were included in this study. The elastic modulus of the macular and peripapillary sclera at the temporal, nasal, superior and inferior regions were determined via shear wave elastography (SWE). Optical coherence tomography and angiography (OCT/OCTA) centered on the fovea and optic disc was obtained by using a commercially available swept-source OCT/OCTA device. Built-in automated software was used to quantify macular subfovea choroidal vessel volume (SFCVV), macular subfovea choroidal thickness (SFCT) and pRNFL thickness.</p> Results <p>The SWE results demonstrated that high myopic eyes had significantly lower macular and peripapillary scleral elastic modulus than low myopic eyes (<i>P</i> &lt; 0.001). The reduction in the elastic modulus was slightly greater in the temporal peripapillary region, followed by the superior peripapillary, inferior and nasal peripapillary regions (<i>P</i> &gt; 0.05). The linear regression analysis demonstrated a significant association between the posterior scleral elastic modulus and SFCT and inferior pRNFL thickness (<i>P</i> &lt; 0.001).</p> Conclusion <p>High myopic eyes had weakened posterior scleral stiffness. The regional change in the elastic modulus was associated with the SFCT and inferior quadrant pRNFL thickness. This novel in vivo quantitative assessment of scleral stiffness via SWE may help to characterize the underlying pathologic mechanism of scleral biomechanics on choroid and pRNFL changes in high myopia.</p> Key messages <Emphasis Type="BoldItalic">What is known</Emphasis> <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Previous studies reported significant choroid thickness and peripapillary nerve fiber layer thickness decrease in high myopia</p> </ItemContent> <ItemContent> <p>The scleral stiffness is weakened in myopic eyes</p> </ItemContent> </UnorderedList></p> <Emphasis Type="BoldItalic">What is new</Emphasis> <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Shear wave elastography (SWE) is a novel tool to detect posterior scleral biomechanics in myopic eyes in vivo</p> </ItemContent> <ItemContent> <p>Stiffness of the posterior sclera at macular and peripapillary regions is lower in high myopic than in low myopic eyes</p> </ItemContent> <ItemContent> <p>The posterior scleral stiffness is correlated with subfovea choroidal thickness and inferior quadrant peripapillary nerve fiber layer thickness</p> </ItemContent> </UnorderedList></p>