Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

PPARγ modulates refractive development and form deprivation myopia in Guinea pigs.

Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferator-activated receptor γ (PPARγ) expression modulate hypoxia-induced pathological responses. We determined if PPARγ modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1α) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPARγ antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1α and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1α expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1α upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPARγ modulates collagen expression levels and FDM through an inverse relationship between changes in PPARγ and HIF-1α expression levels.

Assessment of Choroidal Vascularity and Choriocapillaris Blood Perfusion in Anisomyopic Adults by SS-OCT/OCTA.

Purpose: To explore the association of choroidal vascularity and choriocapillaris blood perfusion with myopic severity in anisomyopes. Methods: Refractive error, axial length (AL), and other biometric parameters were measured in 34 anisomyopic young adults. Macular choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI), were determined from swept-source optical coherence tomography (SS-OCT) vertical and horizontal B-scans. The percentage of choriocapillaris flow voids (FV%) was obtained from en face SS-OCT-angiography. Results: The spherical equivalent refraction (SER) was -3.35 ± 1.25 diopters in the more myopic eyes and -1.25 ± 1.17 diopters in the less myopic eyes (P < 0.001). The interocular difference in SER was highly correlated with that in AL (P < 0.001). The macular ChT, TCA, LA, and SA were smaller in the more myopic eyes than in the less myopic eyes in both vertical and horizontal scans (all P < 0.001). Importantly, the CVIs in vertical and horizontal scans were smaller and the FV% was greater in the more myopic eyes (P < 0.05). In vertical scans, the interocular difference in CVIs was correlated with that in the SER, AL, and ChT (all P < 0.05). The interocular difference in FV% was correlated with that in SER, AL, and vertical and horizontal ChTs (all P < 0.05). Conclusions: Choroidal vascularity and choriocapillaris blood perfusion were lower in the more myopic eyes of anisomyopic adults. These changes were correlated with the severity of myopia and choroidal thinning, indicating that choroidal blood flow is disturbed in human myopia.

Changes in Choroidal Thickness and Choroidal Blood Perfusion in Guinea Pig Myopia.

Purpose: The purpose of this study was to study changes in choroidal thickness (ChT) and choroidal blood perfusion (ChBP), and the correlation between them, in guinea pig myopia. Methods: The reliability of optical coherence tomography angiography (OCTA) for measuring ChT and ChBP was verified in guinea pigs, after cervical dislocation (n = 7) or temporal ciliary artery transection (n = 6). Changes in refraction, axial length, ChT, and ChBP were measured during spontaneous myopia (n = 9), monocular form-deprivation myopia (FDM, n = 13), or lens-induced myopia (LIM, n = 14), and after 4 days of recovery from FDM and LIM. Results: The abolition (by cervical dislocation) or reduction (by temporal ciliary artery transection) of ChBP, and of the associated changes in ChT, were verified by OCTA, thus validating the method of measurement. In the spontaneous myopia group, ChT and ChBP were reduced by 25.2% and 31.9%, respectively. In FDM eyes, mean ± SD ChT and ChBP decreased significantly compared with the untreated fellow eyes (ChT fellow: 76.13 ± 9.34 µm versus 64.76 ± 11.15 µm for FDM; ChBP fellow: 37.87 ± 6.37 × 103 versus 30.27 ± 6.06 × 103 for FDM) and increased after 4 days of recovery (ChT: 77.94 ± 12.57 µm; ChBP: 37.41 ± 6.11 × 103). Effects of LIM were similar to those of FDM. Interocular differences in ChT and ChBP were significantly correlated in each group (FDM: R = 0.71, P < 0.001; LIM: R = 0.53, P < 0.001). Conclusions: ChT and ChBP were significantly decreased in all three models of guinea pig myopia, and they both increased during recovery. Changes in ChT were positively correlated with changes in ChBP. Therefore, it is possible that the changes of ChT are responsible for the changes of ChBP or vice versa.