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Overview of Systemic Pharmacotherapeutics of the Eye

By Nick Whelan, BVSc, MVSc, MACVSc, DACVCP, DACVO, Animal Eye Clinic of Waterloo Region, Cambridge, Ontario, Canada

Also see Ophthalmology.

The anatomy of the eye presents unique opportunities for topical and/or systemic medical treatment of neural tissue. Like the brain, the eye has protective barriers from the vascular system. The blood-ocular barriers (ie, the blood-aqueous and blood-retinal barriers) allow the eye to control entry of inflammatory cells, protein, and low-molecular-weight compounds from the systemic circulation.

The blood-aqueous barrier is a function of the iris and ciliary body epithelium. In the iris, the capillary endothelium is not fenestrated, but there are tight junctions. In the ciliary body, there are tight connections between the apical ends of the nonpigmented epithelial cells. Breakdown of this barrier results in entry of protein and cells into the anterior chamber and is seen as aqueous flare or plasmoid aqueous. The blood-retinal barrier is composed of two layers: an endothelial and epithelial portion. The endothelial part is composed of the endothelium of the retinal capillaries, which are also nonfenestrated. The epithelial portion is the retinal pigment epithelium. When treating the eye via the systemic circulation, these barriers can limit the entry and amount of medications into the eye, especially highly water-soluble compounds. They are less effective in the face of inflammation, and many drugs gain increased access to the intraocular structures when the eye is inflamed. The time required for drugs to reach their peak concentrations in the eye depends highly on the physicochemical properties of the particular drug.

The presence of barriers such as the iris, ciliary body, and lens, as well as normal movement of aqueous humor through the pupil and out the trabecular and uveoscleral meshwork can further limit the distribution of drugs. Several enzymes are present in the cornea and ciliary body. These can metabolize drugs to inactive metabolites before and after the compound reaches the anterior chamber. Drugs predominantly leave the anterior chamber with the aqueous humor via the corneal trabecular and/or uveoscleral meshwork, although small amounts may move posteriorly into the vitreous.