This study aimed to establish a stable mouse model of lens-induced myopia (LIM) and integrate swept-source OCT angiography (SS-OCTA) with quantitative tissue morphology techniques to analyze the spatiotemporal dynamics of retinal structure and blood flow during myopia development. Twenty-four C57BL/6 mice were randomly divided into the LIM group (with the left eye wearing an anti-scratch fixation device and equipped with a -25D lens, n = 12) and the control group (device only, without lens, n = 12). The intervention lasted for 4 weeks. Axial length (AL) and refraction were measured at baseline and 2 and 4 weeks after defocus initiation. The thicknesses of inner, outer, and all retinal layers were quantified in vivo using SS-OCTA at baseline and at weeks 2 and 4 after defocus initiation. At study conclusion, H&E staining was performed for histological analysis of the retina. The LIM group successfully developed progressive myopia (refraction: -2.20 ± 0.79 D vs. 0.13 ± 0.36 D in controls, p < 0.0001) and axial elongation (AL: 3.597 ± 0.042 mm vs. 3.507 ± 0.067 mm, p = 0.0001); SS-OCTA demonstrated significant regional thinning, predominantly in the inner retina of the LIM group, with central thinning of 12.8 % (73.50 ± 18.06 μm vs. 84.38 ± 12.91 μm, p = 0.038); temporal and inferior thinning were also significant. However, there was no statistically significant difference in microvascular density (all p > 0.05). Histology confirmed thinning of the entire temporal retinal layer (12.5 % decrease; 144.70 ± 16.55 μm vs. 165.40 ± 18.46 μm, p = 0.009). Furthermore, the novel fixation device achieved zero detachment rate and did not cause ocular complications. This study successfully established a stable and reproducible LIM model, overcoming technical limitations of traditional methods. Findings indicated that structural remodeling of the inner retina (temporal > central) preceded blood flow alterations, suggesting structural abnormalities as an early driver of myopic axial elongation, providing new insights for targeted myopia interventions.
