Diagnosis and clinical course of ocular ischemic syndrome with retinal vascular abnormalities due to unilateral ocular artery and internal carotid artery stenosis in a child with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a hereditary disease that causes neurofibromas generally, but it has been reported to sometimes be associated with various forms of blood vessel stenosis, occlusion and vascular abnormalities of unknown mechanism. However, a symptomatic case with simultaneous ophthalmic artery stenosis and internal carotid artery stenosis is an extremely rare pathogenesis in a child with NF1. In this report, we performed the diagnosis and observation using various imaging modalities for this rare pediatric case. CASE PRESENTATION: A 6-year-old girl diagnosed with NF1 presented with gradual visual loss in the right eye. Best corrected visual acuity (BCVA) was 20/40 OD and the intraocular pressure (IOP) was normal in both eyes. Retinal vascular abnormalities with tortuous vessels and optic disc pallor were observed in the right fundus. Widefield fluorescein angiography revealed multiple sites of neovascularization and a large non-perfusion area in the peripheral retina. Optical coherence tomography angiography showed retinal vascular abnormalities in the right eye and revealed differences in inner retinal thickness and blood flow signal between the left and right eyes. Laser speckle flowgraphy showed that chorioretinal blood flow was significantly decreased in the right eye. Cerebral angiography revealed the right ophthalmic artery was significantly narrowed throughout. In addition, Magnetic resonance angiography revealed that the right internal carotid artery was significantly narrowed in the ophthalmic segment. We diagnosed ophthalmic artery and internal carotid artery stenosis with retinal vascular abnormalities and ocular ischemic syndrome in NF1. Because IOP increased to 35 mmHg, due to neovascular glaucoma in addition to mild vitreous hemorrhage occurred, panretinal photocoagulation was performed after intravitreal bevacizumab injection. After treatments, IOP normalized, but BCVA decreased to 20/100 OD. Arterial spin labeling showed normal cerebral blood flow. The patient is currently being carefully monitored. CONCLUSIONS: We have described the diagnosis and treatment of ocular ischemic syndrome due to multiple arteries stenosis in a child with NF 1. Utilization of various imaging modalities was helpful in diagnosing the complicated pathogenesis. However, since direct intervention by neurosurgery is not possible in this case, it is expected that treatment will be extremely difficult in the future.

Mesenchymal cells and fluid flow stimulation synergistically regulate the kinetics of corneal epithelial cells at the air-liquid interface.

PURPOSE: In vivo microenvironments are critical to tissue homeostasis and wound healing, and the cornea is regulated by a specific microenvironment complex that consists of cell-cell interactions, air-liquid interfaces, and fluid flow stimulation. In this study, we aimed to clarify the effects of and the correlations among these three component factors on the cell kinetics of corneal epithelial cells. METHODS: Human corneal epithelial-transformed (HCE-T) cells were cocultured with either primary rat corneal fibroblasts or NIH 3T3 fibroblasts. We employed a double-dish culture method to create an air-liquid interface and a gyratory shaker to create fluid flow stimulation. Morphometric and protein expression analyses were performed for the HCE-T cells. RESULTS: Both the primary rat fibroblasts and the NIH 3T3 cells promoted HCE-T cell proliferation, and the presence of fluid flow synergistically enhanced this effect and inhibited the apoptosis of HCE-T cells. Moreover, fluid flow enhanced the emergence of myofibroblasts when cocultured with primary rat fibroblasts or NIH 3T3 cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by both fluid flow and cellular interaction between the HCE-T and NIH 3T3 cells. CONCLUSION: The cell-cell interaction and fluid flow stimulation in the air-liquid interface synergistically or independently regulated the behavior of HCE-T cells. Fluid flow accelerated the phenotypic change from corneal fibroblasts and NIH 3T3 cells to myofibroblasts. Elucidation of the multicomponent interplay in this microenvironment will be critical to the homeostasis and regeneration of the cornea and other ocular tissues.