Essentials of Veterinary Ophthalmology. Kirk N. Gelatt

heavily on choroidal blood flow for nutrients and waste removal. In the animal species studied, most of the blood supply to the choroid is supplied by the short posterior ciliary arteries, but some of the peripheral choroid receives blood from the major arterial circle of the iris. The choroidal capillaries are fenestrated and large (diameter 15–50 μm). These vessels are highly permeable and permit glucose, proteins, and other substances (including fluorescein) of the blood to enter the choroid.

      Within the choroid, these proteins create a high osmotic pressure gradient that assists in removal of fluids from the retina. The short posterior ciliary arteries appear to supply well‐defined territories within the choroid. As a result, these “watershed zones” can develop with marked elevations of IOP (often >50 mmHg), and appear in the dog and nonhuman primate as pyramidal‐shaped areas of choroidal and retinal degeneration extending from the optic nerve head.

      The rate of uveal blood flow is rapid (1.2 ml/min in the cat), with a mean combined retinal and choroidal circulation time of 3–4 s. In monkeys, 95% of the ocular blood flows through the uveal tract, of which 85% is through the choroid. With this high rate of blood flow, oxygen extraction from each millimeter of blood is low (∼5–10%). The oxygen content of choroidal venous blood is 95% of that in arterial blood. Reduced flow rates result in higher oxygen extraction, so that total extraction is reached. This protects the oxygen supply to the retina, and it also protects the eye from light‐generated thermal damage. Choroidal vessels have little to no autoregulatory mechanisms, but carbon dioxide is a potent vasodilator of choroidal vessels. Choroidal vessels are under the strong influence of sympathetic stimulation, which can result in a 60% reduction of choroidal blood flow. The α‐adrenergic drugs cause vasoconstriction of choroidal vessels, but β‐adrenergic drugs have no effect.

      Retinal Blood Flow

      The retina receives 4% of the ocular blood flow in the monkey. In cats, 20% of the oxygen consumed by the retina is delivered through the retinal circulation and the remaining 80% is delivered via the choroidal circulation. Similar data are not available for other domestic animals. Blood flow in the innermost retina is practically unaffected by moderate changes in perfusion pressure. Autoregulation of retinal blood flow is extensive in the cat, monkey, and pig, and protects the retinal circulation from large variations in perfusion pressure. Both metabolic and myogenous autoregulation are present in the eye. Metabolic control of retinal blood flow is similar to that of blood flow to the brain. In the cat, maximum retinal vasodilation occurs with an increased of 75–80 mmHg, so as to increase flow from 15 to 50 ml/min. Neural control of retinal blood flow is limited to those vessels indirectly affecting retinal blood flow. Retinal vessels have α‐adrenergic binding sites that, when stimulated, cause vasoconstriction, thus increasing retinal vascular resistance. Retinal arteries most likely autoregulate through a myogenic mechanism, which is activated based on stretch. During sympathetic stimulation, myogenic autoregulatory responses appear to increase. Opening and closing of capillary beds in many tissues occur with varying metabolic needs. The vascular endothelial cells may produce nitric oxide, endothelins, prostaglandins, and renin–angiotensin products in response to chemical stimuli (e.g., acetylcholine and bradykinin), changes in blood pressure and blood vessel wall stress, changes in local oxygen levels, and other stimuli. As the mechanisms of local autoregulation become better understood, pharmacological modulation of these processes may become possible. The theoretical oxygen diffusion maximum of 143 μm plays a significant role in animal species with avascular retinas; as a result, avascular retinas are usually very thin, and have short photoreceptors, no tapeta, high glycogen levels in the Müller cells, and no retinal taper.

      Blood Flow of the Optic Nerve Head

      Blood flow of the optic nerve head is usually provided primarily by branches from the short posterior ciliary arteries. In humans, cats, and rabbits, optic nerve head blood flow possesses autoregulation over a wide range of IOPs (∼30–75 mmHg), but in humans, this autoregulation is most efficient when IOP is 6–30 mmHg. Ocular perfusion pressure, the relationship between systemic blood pressure and IOP, determines blood flow in the optic nerve head. The autoregulatory capacity of optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure, compared with that induced by increasing the IOP. Studies of blood flow in the optic nerve head have been limited by the small tissue mass involved. The optic nerve head is subjected to several different pressures as well as to the tissue stress at the different levels of the scleral lamina cribrosa.

Ocular Barriers

      Blood–ocular barriers contain endothelial and epithelial tight junctions with varying degrees of “leakiness.” These barriers prevent nearly all protein movement and are effective against low molecular weight solutes such as fluorescein and sucrose. The complexities of these structures differ between the various vascular beds, which allow movement of some substances from one compartment to the other. The two primary barriers within the eye are the blood–aqueous barrier (BAB) and the blood–retinal barrier (BRB). With inflammation, these barriers may be compromised, and allow fibrin and other proteins into the ocular tissues and space. Other minor barriers of the eye exist as well. The zonula occludens of the corneal epithelium prevents the movement of ions and therefore fluid from the tears into the stroma, prevents some evaporation, and protects the cornea from pathogens. The partial obliteration of the intercellular spaces provided by the macula occludens of the corneal endothelial cells prevents bulk flow of AH into the corneal stroma but allows moderate diffusion of small nutrients and water.

      Blood–Aqueous Barrier

      The BAB depends primarily on the tight junctions in the nonpigmented ciliary body epithelium, the nonfenestrated iris capillaries, and the posterior iris epithelium. The anterior BAB in the iris allows transcellular transport by means of vesicles. Paracellular transport is controlled by tight junction extensions. The anterior surface of the iris does not serve as a barrier as it does not have a continuous cellular layer. The epithelial portion of the BAB is the inner, nonpigmented ciliary epithelium, and it controls the flow of fluid into the posterior chamber. The BAB is less effective than the retinal epithelial barrier, because protein can pass into the AH through leakage in other parts of the anterior uvea. Both the ciliary body and choroidal blood vessels are highly fenestrated and thus leak most of their plasma components, including protein, into the stroma. No barrier is present between the AH and the vitreous humor, which allows the diffusion of solutes from the posterior aqueous into the vitreous humor, or between the anterior uvea and the sclera. Breakdown of the BAB is seen clinically as an “aqueous flare” in anterior uveitis or secondary to loss of AH, as in anterior chamber paracentesis.

      Blood–Retinal Barrier

The tight junctions between the retinal pigmented epithelial cells comprise the bulk of the epithelial portion of the BRB. The nonfenestrated retinal capillary endothelium with tight junctions between the cells comprises the endothelial portion of the BRB. The most permeable point of the BRB is the optic nerve head, at which substances from the choroid can pass into the nerve. The choroidal capillaries are highly permeable to permit passage of all low molecular weight compounds and proteins. Thus, nutrients from the choroidal blood supply pass readily into the retinal pigment epithelium, where numerous transport systems account for the selectivity of the barrier and elaborate transcellular pathways exist to pass them on into the retina. This high protein permeability of the choroidal vessels also elevates osmotic pressure, which helps fluid to pass out of the retina. The transport of water from the retina to the choroid is driven by the active transport of chloride to prevent water accumulation in the subretinal space. No significant barrier exists between the vitreous body and the retina.

Aqueous Humor and Intraocular Pressure

      In the normal eye, IOP is generated by flow of AH against resistance, and is necessary to maintain the