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J. J. Chen, N. G. Ghazi; Penetration of Topical Ranibizumab in the Rabbit Eye. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6242.
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The outlook for retaining vision in neovascular age-related macular degeneration (NVAMD) has been greatly improved by the development of the new injectable medication ranibizumab (Lucentis). However, Lucentis is currently administered intravitreally with a significant cumulative risk of endopthalmitis. Administration of Lucentis in the form of eye drops (topical route) would substantially decrease the risks and discomfort associated with the current intravitreal route. This study assesses the penetration of Lucentis (48kDa) through the various eye compartments after topical administration to the eye using a rabbit model.
Lucentis eye drops (25µl) were applied every 2 hours for 12 hours daily to the right eye of 5 rabbits. Intraocular penetration of the drug was assessed at 3, 7, 14, 21, and 28 days following initiation of topical application. At each time point, one of the rabbits was euthanized and both eyes were enucleated and evaluated with confocal immunohistochemistry to assess the pattern of ocular penetration of Lucentis. A sixth rabbit was given an intravitreal injection of Lucentis into the right eye and was sampled at 28 days. The left eye of each rabbit was used as an internal negative control. Rabbit eyes incubated for 24 hours with Lucentis were also used as positive controls.
Compared to the positive and negative controls, confocal immunohistochemistry of the right eyes showed mild Lucentis penetration into the retina after 3 days of topical administration. By 7 days, significant Lucentis penetration into both the anterior and posterior segments of the rabbit eye was evident. Strong Lucentis staining was noted in the cornea, iris, and all layers of the retina, including the photoreceptor layer. Mild staining of the retinal pigment epithelium and choroid was present. Confocal imaging of the left eyes of all rabbits at each time point showed no Lucentis staining.
Topically applied Lucentis penetrates through the cornea and enters the retinal layers after 3-7 days of administration in a rabbit model. This provides evidence that topical Lucentis may be a viable method of administration to treat retinal vascular diseases such as NVAMD.
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