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Masatoshi Murata, Atushi Sanbe, Jung Wha Lee, Saori Murata; Laser-induced intrachoroidal drug delivery system to posterior segment eye disease.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5274.
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The purpose of this study is to investigate the feasibility of laser-induced intrachoroidal dexamethasone (DEX) delivery as a potentially useful therapy for adjusting the most effective drug level to posterior segment eye diseases.
An implant was prepared by dissolving poly(DL-lactide), DEX and indocyanine green (ICG). In vitro release of DEX was evaluated at 7, 14, and 28 days by ELISA. In vivo, a DEX implant was inserted into a rabbit choroid, and 10, 50, or 200 burns of photocoagulation were applied at the implant lesion. After treatment, the vitreous humor was immediately aspirated and the DEX level was measured by LC/MS/MS. Furthermore, the vitreous DEX level was measured at 1, 7, 14, and 28 days after implantation and 50 burns of photocoagulation. The toxicity of the laser-exposed DEX implant was evaluated by ophthalmoscopy and light microscopy. Proliferative vitreoretinopathy (PVR) was induced by injecting human retinal pigment epithelial cell line into the vitreous cavity after DEX implantation and photocoagulation, and anti-proliferative activities were evaluated by grading clinical signs and histopathologic studies. Clinical scores of PVR were classified in five stages according to published criteria.
Photocoagulation significantly increased the DEX release from the implant at 7 days in vitro. In vivo, the DEX implant exposed to 10, 50, and 200 burns of photocoagulation increased the vitreous DEX levels in a dose-dependent manner. The DEX implant applied to 50 burns of photocoagulation significantly increased the vitreous DEX level at 1 and 7 days. The laser-exposed DEX implant showed no retinal abnormalities around the implantation site. In clinical PVR scores, most of eyes in the DEX implant with no photocoagulation had stage 4 or 5 at 28 days. However no eye in the laser-exposed DEX implant developed stage 4 and 5 PVR. The laser-exposed DEX implant group had also shown the inhibition of proliferative tissues on the retinal surface at 28 days histologically.
Laser-induced intrachoroidal DEX delivery controls the DEX level in the vitreous humor and effectively prevents an experimental PVR.
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