Effects of 2 Hz flickering light on refractive state, fundus imaging and visual function of C57BL/6 mice.

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450 µm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.

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.

Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs.

In this study, we explored the predictive role of choroidal blood perfusion (ChBP) and choroidal thickness (ChT) on the development of myopia in guinea pigs. Optical Coherence Tomography Angiography (OCTA) was used to assess the baseline choroidal blood perfusion (ChBP) and choroidal thickness (ChT) in 4-week-old guinea pigs. Refraction and axial length (AL) were measured at baseline. Myopia was induced for one week using form-deprivation (FD) or negative lenses followed by measurements of refraction, axial length and choroidal parameters (ChT and ChBP). The correlations were evaluated between the baseline choroidal values and the magnitude of myopia induced, along with the magnitude of changes in ChT and ChBP after myopia induction. There was a significant correlation between the baseline choroidal parameters and ocular refraction. Myopia induction led to choroidal thinning and less ChBP as well as longer eyes. On the other hand, following exposure to the same non-obstructed visual induction period, the myopic shift was less, and it was associated with thicker choroids and more ChBP at baseline. One week of myopia induction also resulted in thinner choroids and less ChBP, and these declines also correlated with their baseline values. In conclusion, the present study shows that the changes in the baseline choroidal ChT and ChBP parameters are proportional to the magnitude of myopia development and axial elongation in guinea pigs. These significant correlations between baseline ChBP and ChT and myopia development suggest that they may be a viable predictor of this process in guinea pigs.

Effect of red-light therapy on retinal and choroidal blood perfusion in myopic children.

OBJECTIVE: To investigate the effect of repeated low-level red-light therapy (RLRLT) on retinal and choroidal blood perfusion in myopic children. METHODS: Forty-seven myopic children (mean spherical equivalent refractive error [SE]: -2.31 ± 1.26 D; age range: 8.0-11.0 years) were enrolled and received RLRLT (power 2 mW, wavelength 650 nm) for 3 min twice a day, while 20 myopic children (SE: -2.75 ± 0.84 D; age range: 7.0-10.0 years) were included as a control group. All participants wore single-vision distance glasses. Refractive error, axial length (AL) and other biometric parameters were measured at baseline and during follow-up visits in the first, second and fourth weeks after initiation of treatment. Retinal thickness, subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) were obtained using optical coherence tomography (OCT). The percentage retinal vascular density (VD%) and choriocapillaris flow voids (FV%) were measured using en-face OCT angiography. RESULTS: After 4 weeks of treatment, a significant increase in SFCT was observed in the RLRLT group, with an average increase of 14.5 µm (95% confidence interval [CI]: 9.6-19.5 µm), compared with a decrease of -1.7 µm (95% CI: -9.1 to 5.7 µm) in the control group (p < 0.0001). However, no significant changes in retinal thickness or VD% were observed in either group (all p > 0.05). In the OCT images from the RLRLT group, no abnormal retinal morphology related to photodamage was observed. The horizontal scans revealed an increase in TCA, LA and CVI over time (all p < 0.05), while SA and FV% remained unchanged (both p > 0.05). CONCLUSIONS: These findings indicate that RLRLT can enhance choroidal blood perfusion in myopic children, demonstrating a cumulative effect over time.

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.

Change in three-dimensional choroidal vessel network after AR device assisted 1-hour visual task in 2D/3D mode in young healthy subjects.

PURPOSE: The purpose of the study was to investigate the changes of choroidal blood perfusion in different layers and quadrants and its possible related factors after 1 h visual task by augmented reality (AR) device in two-dimensional (2D) and three-dimensional (3D) mode, respectively. METHODS: Thirty healthy subjects aged 22-37 years watched the same video source in 2D and 3D mode separately using AR glasses for 1 h with a one-week interval. Swept-source optical coherence tomography angiography (SS-OCTA) was performed before and immediately after watching to acquire choroidal thickness (ChT), three-dimensional choroidal vascularity index (CVI) of large- and middle-sized choroidal vessels and choriocapillaris flow voids (FV%) at macular and peripapillary area. Near point of accommodation (NPA) and accommodative facility (AF) were examined to evaluate the accommodative ability. Pupil diameters by infrared-automated pupillometer under scotopic, mesopic and photopic condition were also obtained. RESULTS: Compared with pre-visual task, the subfoveal CVI decreased from 0.406 ± 0.097 to 0.360 ± 0.102 after 2D watching (p < 0.001) and to 0.368 ± 0.102 after 3D watching (p = 0.002). Pupil sizes under different illuminance conditions became smaller after both 2D and 3D watching (all p < 0.001). AF increased after both 2D and 3D watching (both p < 0.05). NPA receded in post-3D watching (p = 0.017) while a not significant tendency was observed in post-2D. CONCLUSION: A reduction in subfoveal choroidal blood flow accompanied with pupil constriction was observed immediately after 1 h visual task using AR glasses in 2D and 3D mode. Accommodative facility improved after 2D and 3D watching with AR glasses, whereas decrease in the maximum accommodation power was only found in 3D mode.

Choroidal blood perfusion as a potential "rapid predictive index" for myopia development and progression.

Myopia is the leading cause of visual impairment worldwide. The lack of a "rapid predictive index" for myopia development and progression hinders the clinic management and prevention of myopia. This article reviews the studies describing changes that occur in the choroid during myopia development and proposes that it is possible to detect myopia development at an earlier stage than is currently possible in a clinical setting using choroidal blood perfusion as a "rapid predictive index" of myopia.

Bio-heat transfer simulation of retinal laser irradiation.

Retinopathy is a surgical process in which maladies of the human eye are treated by laser irradiation. A two-dimensional numerical model of the human eye geometry has been developed to investigate transient thermal effects due to laser radiation. In particular, the influence of choroidal pigmentation and that of choroidal blood convection-parameterized as a function of choroidal blood perfusion-are investigated in detail. The Pennes bio-heat transfer equation is invoked as the governing equation, and finite volume formulation is employed in the numerical method. For a 500-µm diameter spot size, laser power of 0.2 W, and 100% absorption of laser radiation in the retinal pigmented epithelium (RPE) region, the peak RPE temperature is observed to be 103 °C at 100 ms of the transient simulation of the laser surgical period. Because of the participation of pigmented layer of choroid in laser absorption, peak temperature is reduced to 94 °C after 100 ms of the laser surgery period. The effect of choroidal blood perfusion on retinal cooling is found to be negligible during transient simulation of retinopathy. A truncated three-dimensional model incorporating multiple laser irradiation of spots is also developed to observe the spatial effect of choroidal blood perfusion and choroidal pigmentation. For a circular array of seven uniformly distributed spots of identical diameter and laser power of 0.2 W, transient temperature evolution using simultaneous and sequential mode of laser surgical process is presented with analysis.