Quantitative retinal alterations in hyperopic defocus: Integrated OCT angiography and histomorphometric analyses of lens-induced murine myopia.

Abstract

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&#xa0;=&#xa0;12) and the control group (device only, without lens, n&#xa0;=&#xa0;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&#xa0;&#xb1;&#xa0;0.79 D vs. 0.13&#xa0;&#xb1;&#xa0;0.36 D in controls, p&#xa0;<&#xa0;0.0001) and axial elongation (AL: 3.597&#xa0;&#xb1;&#xa0;0.042&#xa0;mm vs. 3.507&#xa0;&#xb1;&#xa0;0.067&#xa0;mm, p&#xa0;=&#xa0;0.0001); SS-OCTA demonstrated significant regional thinning, predominantly in the inner retina of the LIM group, with central thinning of 12.8&#xa0;% (73.50&#xa0;&#xb1;&#xa0;18.06&#xa0;&#x3bc;m vs. 84.38&#xa0;&#xb1;&#xa0;12.91&#xa0;&#x3bc;m, p&#xa0;=&#xa0;0.038); temporal and inferior thinning were also significant. However, there was no statistically significant difference in microvascular density (all p&#xa0;>&#xa0;0.05). Histology confirmed thinning of the entire temporal retinal layer (12.5&#xa0;% decrease; 144.70&#xa0;&#xb1;&#xa0;16.55&#xa0;&#x3bc;m vs. 165.40&#xa0;&#xb1;&#xa0;18.46&#xa0;&#x3bc;m, p&#xa0;=&#xa0;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&#xa0;>&#xa0;central) preceded blood flow alterations, suggesting structural abnormalities as an early driver of myopic axial elongation, providing new insights for targeted myopia interventions.