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H. Kim, W. He, S. B. Robinson, S. W. Cousins, K. G. Csaky; The Effects of Lymphatic Clearance on the Transcleral Penetration of Sodium Fluorescein (NaF) in Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1815.
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© ARVO (1962-2015); The Authors (2016-present)
Transscleral delivery into the vitreous using a subconjunctival drug implant is under investigation but appears to be hampered by low sustained vitreous drug levels in animals. To improve our understanding of the clearance mechanism in transscleral delivery, we evaluated intraocular fluorescence levels following subconjunctival implantation of NaF in rats with decreased conjunctival lymphatic outflow.
To quantify fluorescein penetration into the retina, pixel standardization was performed and standard curves were generated in 8 µm slices. A 2% NaF- HPMC implant was placed in the subconjunctival space. The buccal lymphatic vessel was visualized after subconjunctival injection of patent blue dye and either ligated or sham-ligated. One hour post- implantation, the eye and buccal lymph node were enucleated and frozen immediately using OCT. Sections were prepared and fluorescent intensity in the retina and lymph node of control, euthanized, lymphatic ligated or sham-ligated animals was quantified.
Intraocular fluorescence was significantly elevated in euthanized animals compared with controls. Ten minutes after subconjunctival injection of patent blue dye, the blue dye was observed within the buccal lymphatic vessel. Ligation of the lymphatic vessel inhibited the appearance of NaF into the buccal lymph node. A significant elevation of intraocular fluorescence was detected in the ligated side retina than in the non-ligated side retina (p < 0.005).
These results suggest that the conjunctival lymphatic vessels effectively eliminate hydrophilic agents from the subconjunctival space and thereby may reduce their ocular penetration. The various periocular drug clearance modalities are important to consider when developing a successful transscleral drug delivery system.
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