Also see Ophthalmology.
The eye and surrounding tissues present opportunities for topical and/or systemic medical treatment. Like skin, the eye is visible and medication can be applied directly in some instances, but at other times systemic administration is the better option for optimal response.
Ocular Anatomy in Animals
The globe is held in position in the orbit by the extraocular muscles, which allow horizontal, vertical, and rotatory movement as well as movement into the orbit. The upper, lower, and third eyelids have several functions that include protecting the globe, contributing the lipid layer of the tear film, spreading the tear film, and helping to decrease evaporation. The cornea and sclera make up the outer fibrous coats of the eye and are a directly visible physical barrier. The interior of the globe is separated into anterior and posterior segments. The anterior segment consists of the anterior chamber (aqueous humor), anterior uvea (iris/pupil and ciliary body), and lens. Behind this is the vitreous and the posterior uvea, which is composed of the retina, choroid, and optic nerve.
Ocular Therapeutics in Animals
Medication administration for ocular disorders is affected by interactions involving the eye and the drug, both of which are influenced by the route of administration and the class of drug.
Eye Effects
The eye affects administration of an ocular drug by controlling absorption/penetration (the practitioner should make note of rate/pharmacokinetics) of absorption, distribution, metabolism, and excretion. These can be affected by physicochemical factors associated with the cornea and blood-ocular barriers. The cornea has four layers:
epithelium
stroma
Descemet membrane
endothelium
Each of these layers can impede movement of drugs into the anterior chamber. Drug penetration through the cornea is limited by its physical makeup. The epithelial layer is the major barrier to absorption because of its tight cellular junctions and its lipophilic nature. The lipophilic endothelium is also a barrier to hydrophilic drugs but not to the same extent as the epithelium. The hydrophilic corneal stroma, by contrast, is more of a barrier to lipophilic than to hydrophilic drugs. To penetrate the corneal epithelium, a drug needs to be lipophilic or non-ionized. Further movement across the stroma requires the drug to have a hydrophilic component or for it to be ionized. Passage across Descemet membrane and the endothelium into the anterior chamber requires the drug to be non-ionized.
Like the brain, the eye has protective barriers from the vascular system. The two protective barriers within the globe, known as the blood-ocular barriers, are the blood-aqueous and the blood-retinal barriers. They 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 occurs as aqueous flare or plasmoid aqueous.
The blood-retinal barrier is composed of two layers: an endothelial and an epithelial portion. The endothelial part is composed of the endothelium of the retinal capillaries, which are nonfenestrated. The epithelial portion is the retinal pigment epithelium. The presence of other 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 active or 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. When treating the eye via the systemic circulation, these barriers can limit the entry and amount of medications into the eye, especially for highly water-soluble compounds. These barriers 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.
Drug Effects
In addition to the effects of the eye, there are also effects of the drug. These depend on the route of administration, the formulation vehicle and its release characteristics, and the volume administered.
For More Information
Also see pet health content regarding drugs used to treat eye disorders.
