A Duration-Dependent Interaction Between High-Intensity Light and Unrestricted Vision in the Drive for Myopia Control.

Purpose: To evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and unrestricted vision (UnV) on lens-induced myopia (LIM) development in chickens. Methods: Myopia was induced in one eye in chicks (10 groups, n = 126) from day 1 posthatching (D1) until day 8 (D8) using -10 diopter (D) lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to 2, 4, or 6 hours of HL (15,000 lux), UnV (removal of -10 D lens), or both (HL + UnV). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as interocular difference (IOD = experimental eye - control eye) ± SEM. Results: By D8, LIM increased AL (0.36 ± 0.04 mm), myopic refraction (-9.02 ± 0.37 D), and choroidal thinning (-90.27 ± 16.44 µm) in the LIM group (all, P < 0.001). Compared to the LIM group, exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced myopic refraction in a duration-dependent manner, with UnV being more effective than HL (P < 0.05). Only 6 hours of HL + UnV (not 2 or 4 hours) prevented LIM and was more effective than UnV (P = 0.004) or HL (P < 0.001) in reducing myopic refraction and more effective than HL (P < 0.001) in reducing axial elongation. Conclusions: Daily exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6 hours of HL + UnV completely stopped LIM development. The synergetic effect of HL and UnV is dependent on the duration of the interventions.

Evaluation of a steroid delivery system to mitigate the severity of proliferative vitreoretinopathy in a minipig model.

Purpose: To investigate the efficacy of liposomal prednisolone phosphate to mitigate the severity of proliferative vitreoretinopathy (PVR) in a minipig model of PVR. Methods: A total of 18 eyes of 9 minipigs underwent PVR induction surgically. Eyes were randomized equally into three groups: intravitreal injection of liposomal prednisolone phosphate (LPP), triamcinolone acetonide (TA), and controls. PVR severity was graded on fundoscopic examination using a modified version of the Silicon Study Classification System. Severe PVR was defined as grade 2-5 on this classification, and the proportion of eyes with retinal detachment from severe PVR, defined as retinal re-detachment, i.e., PVR grade 2-5, was compared between treatment and control groups. Results: On day 28, five eyes (83.3%) in the control group were observed to have severe PVR. Within the LPP group, one (16.7%) eye developed retinal detachment due to severe PVR. Grade 0 PVR was observed in four (66.7%) eyes, grade 1 in one (16.7%) eye, and grade 5 in one (16.7%) eye. Within the TA group, grade 0 PVR was observed in four eyes (66.7%), grade 1 in two eyes (16.6%), and grade 5 in one (16.7%) eye. The difference in the proportion of eyes with severe PVR was significantly lower in the LPP group compared to controls at day 28 (16.7% vs 83.3%, p=0.02). There was no significant difference in the rate of severe PVR or median PVR grade between the liposomal prednisolone phosphate and triamcinolone acetonide groups. Conclusion: Liposomal prednisolone phosphate reduces the severity of PVR in a minipig model of PVR.

Endogenous or Exogenous Retinal Pigment Epithelial Cells: A Comparison of Two Experimental Animal Models of Proliferative Vitreoretinopathy.

Purpose: Proliferative vitreoretinopathy (PVR) is a blinding condition that can occur following ocular penetrating injury and retinal detachment. To develop effective therapeutics for PVR, it is imperative to establish an animal model that is reproducible, closest in anatomy to the human eye, and most representative of the human disease. We compared two in vivo models of PVR in minipig eyes to assess reproducibility and consistency. Methods: Six minipigs underwent PVR induction with procedure A and six underwent procedure B. In both procedures, PVR was induced with vitrectomy, bleb retinal detachment, retinotomy, and injection of platelet-rich plasma. In procedure A, retinal pigment epithelial (RPE) cells were harvested from cadaveric pig eyes and injected at the end of surgery. In procedure B, native RPE cells were released into the vitreous cavity by creating a RPE detachment and scraping the RPE layer. PVR severity was graded on fundoscopic examination with a modified Silicone Study Classification System for PVR. Severe PVR was defined as stages 2 to 5. Results: Three eyes (50%) and five eyes (83.3%) developed re-detachment of the retina from severe PVR in procedures A and B, respectively (P = 0.55). Median PVR stage was higher in eyes that underwent procedure B compared to eyes that underwent procedure A, although the difference was not statistically significant (2.5 vs. 1.5, P = 0.26). Conclusions: This new model utilizing native RPE cells achieved a high consistency in inducing severe PVR in the minipig. Translational Relevance: Our model closely follows pathogenic events in human PVR, making it ideal for preclinical testing of novel therapeutics for PVR.