Essentials of Veterinary Ophthalmology. Kirk N. Gelatt

Table 2.11 Factors that cause short‐ and long‐term fluctuations in IOP.

Short‐term fluctuations	Long‐term fluctuations
Diurnal changes	Aging
Forced eyelid closure	Race/breed
Contraction of retractor bulbi muscles	Hormones
Coughing/Valsalva maneuver	Glucocorticoids
Abrupt changes in blood pressure	Growth hormone
Pulse	Estrogen
Struggling/electroshock	Progesterone
Changes in body/head position	Obesity
Succinylcholine	Myopia
Acidosis	Gender
	Season

      Ocular rigidity is a constant characteristic of each eye, but it also depends on IOP. Hence, the distensibility of each globe varies among individuals as well as with the IOP. Dogs and cats have greater scleral elasticity than humans, so less resistance is offered with indentation tonometry, and buphthalmia occurs more readily with prolonged, increased IOP.

      Intraocular Pressure

In many species, IOPs as measured with applanation tonometry in normal animals have been reported (Table 2.10). In humans and animals, short‐ and long‐term fluctuations in IOP occur for a variety of reasons (Table 2.11). Diurnal IOP variations generally occur in most species; in humans and dogs, the highest pressure occurs in the morning and the lowest in the afternoon. In contrast, the greatest IOPs occur during the day and the lowest IOPs are documented at night in the rabbit, cat, horse, and nonhuman primate. In glaucomatous canine patients, diurnal IOP fluctuations (as measured by tonometry) are typically much greater in comparison to normal dogs. Consequently, antiglaucoma medications administered once daily to dogs should be given in the evening to mitigate IOP spikes in the morning, when pressures are typically the greatest.

Lens

      The second most powerful refracting structure in the eye is the lens. Like the cornea, the lens is a transparent tissue without a direct blood supply. The lens depends primarily on AH for its metabolic needs. Most of the lens proteins are soluble, with a small amount of glycoproteins, whereas the cornea consists mostly of insoluble collagen and a relatively large amount of glycoproteins. The lens considerations are important to the veterinary ophthalmologists when considering cataract surgery in animals, and attempts using intraocular lenses (IOLs) to re‐establish the best possible visual acuity. Lens metabolism is also important as the second largest group of dogs having cataract surgery are those with diabetes mellitus.

      Lens epithelial cells are the progenitors of the lens fibers and transition into lens fiber cells of the cortex at the equator. This process is characterized by distinct biochemical and morphological changes, such as the synthesis of crystallin proteins, cell elongation, loss of cellular organelles, and disintegration of the nucleus.

      Transparency of the lens depends primarily on the highly ordered lens cell arrangement, as well as on the solubility and physical arrangements of its proteins. The lens behaves as a cell syncytium both biochemically and electrically. The lens consists of approximately 68% water, 38% protein, and small amounts of lipids, inorganic ions, carbohydrates, ascorbic acid, glutathione, and amino acids.

      The protein content of the lens is very high in comparison to other body organs. Protein synthesis ceases with formation of the lens fiber cells, and all the protein changes that occur after this stage are posttranslational modifications. Lens proteins are divided into water‐soluble proteins and water‐insoluble proteins. Crystallins comprise 80–90% of the water‐soluble lens proteins. Most of the insoluble proteins occur in the lens nucleus, whereas the soluble proteins are concentrated in the lens cortex. The insoluble proteins are associated primarily with membranes of the lens fibers; the soluble proteins comprise the bulk of the refractive fibers of the lens. With aging, water‐soluble proteins coalesce to make high molecular weight aggregates and their hydrophilicity diminishes. Additionally, when the lens becomes cataractous, the level of water‐insoluble proteins increases.

      The lens epithelium is the major site of energy production in the lens. Energy is used for active transport of inorganic ions and amino acids and for protein synthesis. Osmoregulation occurs through active transport and involves the action of Na⁺–K⁺‐ATPase to maintain high K⁺ and amino acid concentrations and low Na⁺, Cl⁻, and water concentrations within the lens. The movement of water is passive and occurs with the active cation transport. As the Na⁺ ion is transported from the lens, K⁺ is transported into the lens (see Figure 2.7) in a manner similar to that in red blood cells.

The lens capsule functions as a semipermeable membrane. It prevents direct contact between the lens and the surrounding ocular environment and protects the lens from the invasion of pathogens. However, the capsule allows water, small solutes, many proteins, and waste to pass, thereby enabling the lens to grow and perform metabolic functions. Its mechanical functions include maintaining the shape of the lens in association with accommodating and providing for the attachment of the zonules. Because the lens capsules surround the developing lens before the fetus's immune system develops, leakage of lens cells and material causes lens‐induced uveitis in later life (a major cause for lower cataract surgery success results in the long term).

      The primary source of energy for the lens is glucose, which diffuses from the AH. Energy is derived from anaerobic glycolysis and is used for active cation transport and protein synthesis. Oxygen is not necessary for normal lens metabolism, though a small percentage of glucose is metabolized through the Krebs cycle. The hexose monophosphate (i.e., pentose) shunt and the sorbitol pathway are other pathways of glucose metabolism in the lens. The major end product of glucose metabolism in the lens is lactic acid, which diffuses into the AH. The rate of glycolysis is controlled by the amount of hexokinase enzyme and the rate of entrance of glucose into the lens. With high concentrations of glucose (>175 mg/dl), the level of glucose 6‐phosphate increases, which inhibits hexokinase and limits the rate of glycolysis. This process prevents excessive buildup of lactic acid in the lens, which would lower the pH and activate the lens proteases. With very high blood and AH glucose concentrations, as occur in diabetes mellitus, the enzyme aldose reductase is activated as an alternative route of glucose metabolism in the lens. The result is an accumulation of sorbitol in the lens cells, which causes swelling associated with the increased osmotic pressure. The outcome is the intumescent diabetic cataract.

Vitreous

      Vitreal Structure and Aging

      Physically, the vitreous is a hydrogel that consists of >98% water and fills the large posterior cavity of the eye. Collagen comprises the framework of the vitreous and provides its plasticity. Despite the low protein content, a diverse array of >1200 soluble proteins have been identified