Ординатура / Офтальмология / Английские материалы / Slatter's Fundemental of Vetrinary Ophthalmology 4th edition_Maggs, Miller, Ofri_2008

Lens vesicle cavity

Posterior epithelial cells elongating into primary lens fibers

FIGURE 2-15. Light micrograph of 15-mm pig embryo showing lens vesicle filling with primary lens fibers; lens bow configuration is evident. (Modified from Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

posterior tunica vasculosa lentis (Figure 2-19). The anterior tunica vascuolosa lentis is formed by branches from the annular vessel. These tunicas are responsible for vascular supply to the lens during embryonic development. During the last stages of embryologic development or soon after birth, as the aqueous humor takes over this metabolic function, the hyaloid vasculature atrophies, regresses, and is replaced by the pupillary membrane (see also next section, Ciliary Body and Iris).

The mesenchyme around the optic cup forms the choroid, which surrounds the choriocapillaris. The nasal and temporal long posterior ciliary arteries branch off the ophthalmic artery and advance forward in the horizontal plane through the choroid to supply the future ciliary body. At the level of the ciliary body they anastomose to form the major vascular circle of the iris.

Posteriorly, the short ciliary arteries arrange themselves around the entrance of the optic nerve into the globe (Figure 2-20). The vessels form an anastomosing plexus, called the Haller-Zinn vascular circle, which plays a role in the vascular supply of the optic nerve head.

Ciliary Body and Iris

The adult ciliary body is lined with two layers of epithelium of neuroectodermal origin. The inner layer, close to the vitreous, is unpigmented. This layer is the anterior extension of the sensory neuroretina, though it contains no neural elements. The outer layer is pigmented and is the anterior continuation of the retinal pigment epithelium. The ciliary epithelium forms folds called ciliary processes (Figure 2-21). These processes are the production site of the aqueous humor; they also serve as the anchoring site of the lens zonules, which suspend the lens in the eye. The underlying ciliary muscle and stroma of the ciliary body originate from the neural crest–derived secondary mesenchyme; the power of the muscle’s contraction and relaxation is transferred through the ciliary processes and zonules to the lens, changing its refraction and the focusing of the eye.

The anterior rim of the optic cup forms the iris, which has two pigmented epithelial layers on its posterior face. These epithelial layers are continuous with the two layers of the epithelium of the ciliary body. The sphincter and dilator smooth muscles of the mammalian iris, which control the constriction and dilation of the pupil through their antagonistic actions, are

DEVELOPMENT AND CONGENITAL ABNORMALITIES 27

A B

C D

E F

G H

FIGURE 2-16. Stages of development of the lens. A, Elongation and anterior growth of posterior cuboidal epithelial cells to form primary lens fibers. B, Elongation of primary lens fibers to fill the cavity in the lens vesicle, and formation of the lens bow of cuboidal cell nuclei. C and D, Secondary lens fibers proliferate from the equatorial region of the lens, covering the primary lens fibers and scattered cuboidal cell nuclei. E, The adult lens. F and G, Appearance of the Y sutures. H, New layers of secondary lens fibers are laid down around the central primary lens fibers. Growth continues throughout life. (A modified from Severin GA [2000]: Severin’s Veterinary Ophthalmology Notes, 3rd ed. Severin, Ft. Collins, CO.)

derived from the neuroectoderm of the anterior rim of the optic cup. The iris stroma originates from the neural crest–derived secondary mesenchyme (see Figure 2-21). This mesenchyme continues to grow over the anterior part of the lens, covering the hole that will be the future pupil with a membrana pupillaris, which replaces the anterior tunica vasculosa lentis at the same location (see Figures 2-19 and 2-22). This membrane contains branches from the major arterial circle of the iris that form a vascular net over the iris and the pupil. However, strands of the membrana pupillaris may remain attached to the anterior surface of the iris. These strands, known as persistent pupillary membranes, are inherited as a homozygous recessive trait in the basenji.

Posterior capsule

FIGURE 2-17. Adult lens showing the successive layers of the lens that are laid around the embryonal nucleus throughout life. (From Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. ButterworthHeinemann, St. Louis.)

FIGURE 2-18. Lens embryogenesis. Left, Elongation of the posterior epithelium results in obliteration of the lens lumen. Right, Secondary lens fiber migration leads to the formation of the Y sutures. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

Anterior vascular capsule (pupillary membrane)

Posterior vascular capsule

Capsulopupillary portion

Hyaloid artery

FIGURE 2-19. Hyaloid vasculature and primary vitreous during embryologic ocular development. (From Yanoff M, Duker J [2004]: Ophthalmology, 2nd ed. Mosby, St. Louis.)

vessels

Retinal blood vessels

Vortex vein

Long posterior ciliary artery

Short posterior ciliary arteries

Central retinal artery

Central retinal vein

FIGURE 2-20. Horizontal section of the eye showing ciliary circulation. (From Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

Cornea and Anterior Chamber

The outer corneal epithelium derives from the surface ectoderm, but the inner layers, which include the corneal stroma and corneal endothelium, derive from the secondary mesenchyme. Descemet’s membrane is secreted by the endothelial cells (see Figure 2-22). Further ingrowth of secondary mesenchyme occurs between the epithelium and endothelium, forming the corneal stroma.

Between the cornea and the lens two spaces develop: the posterior chamber between the iris and the lens, and the anterior chamber between the iris and the cornea (Figure 2-23). After the regression of the pupillary membrane, aqueous may flow from the posterior chamber to the anterior chamber through the pupil.

Sclera and Extraocular Muscles

Neural crest–derived mesenchyme surrounds the optic cup and forms two layers. The inner layer, which is adjacent to the retina, is the choroid, and the outer layer is the sclera. Condensation of the sclera begins anteriorly, near the ciliary body, and proceeds posteriorly to the optic nerve, where it is continuous with the dura mater of the optic nerve. Extraocular muscles form in the neural crest–derived secondary mesenchyme of the orbit.

Eyelids and Third Eyelid

The lower eyelid and the third eyelid are formed by the maxillary process. The upper eyelid is formed by the paraxial mesoderm. During development the upper and lower eyelids are fused (Figure 2-24). With time, these fused eyelids separate, although the age at which separation occurs varies among species. In horses, cattle, sheep, and pigs, lids open at 7 to 10 days postpartum. During the formation of the eyelids their inner surface

Conjunctiva

Outer, pigmented epithelium

Ciliary body

Sclera

A

B

Future cornea

Descemet endothelium (mesothelium)

Pupillary Posterior membrane chamber

Mesoderm

FIGURE 2-22. Formation of the anterior chamber and cornea. Note the pupillary membrane, which replaced the anterior tunica vasculosa lentis, covering the future pupil.

Fused Anterior Posterior

Cornea lids chamber chamber

4 mm

Hyaloid artery

Retina

FIGURE 2-23. Section through eye and orbit of 48-mm human embryo (approximately 9.5 weeks). (Modified from Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

(and the anterior sclera) is lined with palpebral conjunctiva derived from the surface ectoderm. This ectoderm also contributes to the formation of lid epidermis, cilia, and a number of glands: the lacrimal and nictitating glands, which produce the aqueous portion of the tear film; the tarsal meibomian glands, which produce the lipid component of the tear film; and Zeiss (sebaceous) and Moll (sweat) glands. Neural crest–derived secondary mesenchyme contributes to the development of the

tarsus and dermis of the lids, but mesoderm contributes to the formation of eyelid muscles.

Nasolacrimal System

The nasolacrimal groove separates the lateral nasal fold from the maxillary processes. At the bottom of the groove a solid cord of ectodermal cells forms and gets buried as the maxillary

Anterior chamber

FIGURE 2-24. Light micrograph of 45-mm pig embryo. Eyelids are fused, extraocular muscle is evident, and axons are evident in optic nerve. (Modified from Remington LA [2005]: Clinical Anatomy of the Visual System, 2nd ed. Butterworth-Heinemann, St. Louis.)

process grows over it to fuse to the lateral nasal fold. Two ectodermal buds grow from the proximal end of the buried cord toward the upper and lower lid folds near the nasal canthus. These buds form the superior and inferior lacrimal puncta. The distal end of the cord enters the ventral nasal meatus. The entire cord becomes the nasolacrimal duct by a process of canalization. Incomplete canalization is common in domestic animals, resulting in obstruction of the tear drainage. In dogs the puncta and the upper half of the nasolacrimal duct are most commonly affected. In horses the nasal meatus of the duct may be imperforate.

CONGENITAL ABNORMALITIES

Teratology is the branch of embryology that deals with abnormal development and congenital malformations. It is important to remember that not all congenital abnormalities are necessarily inherited, as some may result from toxicity or disease during development. Conversely, not every inherited abnormality is necessarily congenital. Many inherited disorders (e.g., cataract, progressive rod cone degeneration) may be manifested later in life.

The most important determining aspect of the character of a deformity is the stage of development at which the etiologic agent acts. Factors acting during the early period of embryogenesis are generally lethal. Those occurring during organogenesis result in gross deformities affecting the whole eye (e.g., anophthalmia, microphthalmia, and cyclopia). If the factor acts during the fetal period, when the most fundamental and active stage has been completed, minor defects of individual parts of the eye caused by arrests in development and associated deformities due to aberrant growth may occur. Because much of the development and differentiation of the eye occurs very early in gestation (during the first 2 weeks in the dog), events initiated during this time may result in malformations in structures that do not fully mature until much later. Studies of the effect of exposure to teratogens on ocular development have identified narrow, critical periods for induction of malformations; for example, exposure during gastrulation (formation of the mesodermal germ layer) results in a spectrum of malformations

including microphthalmia, cataract, retinal dysplasia, anterior segment dysgenesis, and optic nerve hypoplasia. It is only by detailed study of anomalies that etiology and pathogenesis of the lesions are understood, and subsequent diagnosis and evaluation simplified.

The stage of development (e.g., embryogenesis, organogenesis, or fetal period) at which a teratogenic factor acts is most important in determining the final effects on the eye.

In this section common congenital abnormalities of the whole eye of domestic animals are considered. Abnormalities of the individual parts of the eye are discussed in the relevant chapters.

Anophthalmos and Microphthalmos

Anophthalmos means the total absence of an eye. It may be caused by the suppression of the optic primordia during the development of the forebrain, may be caused by the abnormal development of the forebrain, or may be due to the degeneration of the optic vesicles after they have already formed as a result of a teratogenic insult.

True anophthalmos is very rare, and its diagnosis is made after histologic examination of the orbital contents has not shown the presence of any ocular structure. Most instances of presumed clinical anophthalmos are cases of extreme microphthalmos, because some histologic evidence of a rudimentary eye can usually be found.

Microphthalmos is an eye that is smaller than normal (Figure 2-25). Microphthalmos is most frequent in pigs and

A

B

FIGURE 2-25. A, Bilateral microphthalmia as part of a multiple ocular defects syndrome, which also includes developmental defects in the iris, lens, retina and embryonic hyaloid apparatus. B, Close-up of the right eye of the same dog, highlighting the microphthalmia and iris abnormalities. (Courtesy University of California, Davis, Veterinary Ophthalmology Service Collection.)

Table 2-1 Anomalies Associated with Microphthalmos in Dogs

Modified from Cook C (1995): Embryogenesis of congenital eye malformations. Vet Comp Ophthal 5:110.

dogs. In pigs, vitamin A deficiency in the dam is the most common cause. In dogs, microphthalmos occurs frequently as part of the collie eye anomaly. Administration of griseofulvin to pregnant cats for treatment of dermatomycosis has resulted in anophthalmos or microphthalmos in their kittens. In white shorthorn cattle hereditary microphthalmos is associated with large lids and third eyelid, resulting in entropion because the small globe does not support the elongated lids.

Microphthalmos may occur in eyes that are otherwise (functionally) normal, if all the internal eye structures remain proportional in size. It may also occur in eyes with multiple ocular anomalies, including cataract, retinal dysplasia, and anterior segment dysgenesis (Table 2-1). In Jersey calves, an autosomal recessive condition causes congenital blindness with microphthalmos, aniridia (lack of iris), microphakia (small lens), ectopia lentis (malpositioned lens), and cataract. Lambs grazing on seleniferous pasture in Wyoming were afflicted with microphthalmos, ectopia lentis or aphakia, optic nerve hypoplasia, persistent pupillary membrane, uveal coloboma, and nonattachment of the retina. In Hereford cattle an encephalopathymicrophthalmos syndrome is inherited as a simple autosomal recessive hereditary trait. Animals present with a domed skull, degeneration of skeletal muscles, small palpebral fissures, small orbits, retinal dysplasia, vitreous syneresis, microphakia, and bilateral microphthalmos.

Cyclopia and Synophthalmus

In cyclopia there is a single eye. In synophthalmus the eyes are fused in the midline (Figure 2-26). These conditions are incompatible with life.

2-26. Cyclopia in lambs whose dam grazed on Veratrum californicum. (Courtesy University of Wisconsin–Madison Veterinary Ophthalmology Service Collection.)

DEVELOPMENT AND CONGENITAL ABNORMALITIES 31

In cyclopia the prosencephalon does not show cleavage; there is one midbrain, one dorsal cyst, and a single optic nerve and optic canal. The frontonasal process presents a proboscis (displaced nose) above the single orbit. The lids of the two eyes are fused around the single orbit. Cyclopia has been reported, in Idaho and Utah, in lambs born to ewes that grazed on Veratrum californicum on the fourteenth day of gestation and, in Western Australia, in lambs born to ewes that grazed on unknown toxic plants.

Coloboma

Coloboma is a condition in which a portion of the eye, usually a portion of the uvea, is lacking. Most colobomas (typical colobomas) are due to an incomplete closure of the embryonic optic fissure (Figure 2-27). These colobomas are usually situated in the inferonasal portion of the eye. The extent of the coloboma may vary. Severe colobomas are associated with the formation of an orbital cyst (microphthalmos with orbital cyst), because the optic fissure failed to close and form a vesicle. Moderate colobomas may involve numerous ocular structures, whereas mild cases may manifest as only a simple notch in the lower nasal quadrant of the pupil.

Atypical colobomas are not associated with the incomplete closure of the embryonic fissure and are not located in the lower nasal quadrant. They are usually due to lack of induction of one tissue by another. For example, lack of induction by retinal pigment epithelium may cause colobomas in the choroid and sclera, whereas lack of induction by the anterior rim of the optic cup may result in aniridia, or lack of iris.

Colobomas of the optic nerve head may be seen in dogs affected with collie eye anomaly (Figure 2-28) and in basenjis that present with persistent pupillary membranes. In cats,

Mesodermal vascular tissue

Retina

Pigment epithelium

Retina

Pigment epithelium

FIGURE 2-27. The closure of the fetal cleft. The margins come together accurately (top), but subsequently an excessive growth of the inner (retinal) layer leads to its eversion (bottom), causing a coloboma of the retina and posterior uvea. (Modified from Duke-Elder S [editor] [1963]: System of Ophthalmology, Vol III: Normal and Abnormal Development. Part 2: Congenital Deformities. Henry Kimpton, London.)

FIGURE 2-28. A coloboma of the optic nerve head and sclera as part of the collie eye anomaly syndrome.

colobomas in the lateral segments of the upper eyelids are common. These must be surgically corrected, because they allow facial hair to irritate the cornea and conjunctiva.

BIBLIOGRAPHY

Achiron R, et al. (2000): Axial growth of the fetal eye and evaluation of the hyaloid artery: in utero ultrasonographic study. Prenat Diagn 20:894.

Aguirre G, et al. (1972): The development of the canine eye. Am J Vet Res 33:2399.

Bailey TJ, et al. (2004): Regulation of vertebrate eye development by Rx genes. Int J Dev Biol 48:761.

Baker CV, Bronner-Fraser M (2001): Vertebrate cranial placodes I: embryonic induction. Dev Biol 232:1.

Barishak RY (2001): Embryology of the Eye and Its Adnexa. S. Karger, Basel, Switzerland.

Bistner SI, et al. (1973): Development of the bovine eye. Am J Vet Red 34:7. Boroffka SA (2005): Ultrasonographic evaluation of preand postnatal

development of the eyes in beagles. Vet Radiol Ultrasound 46:72. Collinson JM, et al. (2004): Analysis of mouse eye development with

chimeras and mosaics. Int J Dev Biol 48:793.

Cook C (1995): Embryogenesis of congenital eye malformations. Vet Comp Ophthal 5:110.

Cook C, et al. (1993): Prenatal development of the eye and its adnexa, in Tasman Jaeger W (editor): Duane’s Foundations of Clinical Ophthalmology. JB Lippincott, Phildelphia, p. 1.

Cook CS (1989): Experimental models of anterior segment dysgenesis. Ophthalmic Paediatr Genet 10:33.

Cvekl A, Tamm ER (2004): Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases. Bioessays 26:374.

Duddy JA, et al. (1983): Hyaloid artery patency in neonatal beagles. Am J Vet Res 44:2344.

Gould DB, et al. (2004): Anterior segment development relevant to glaucoma. Int J Dev Biol 48:1015.

Gum GG, et al. (1984): Maturation of the retina of the canine neonate as determined by electroretinography and histology. Am J Vet Res 45:1166.

Jubb KF, Kennedy PC (1993): Pathology of the Domestic Animals, 4th ed, Vol II. Academic Press, New York.

McAvoy JW, et al. (1999): Lens development. Eye 13:425.

Mey J, Thanos S (2000): Development of the visual system of the chick:

I. Cell differentiation and histogenesis. Brain Res Brain Res Rev 32:343. Pichaud F, Desplan C (2002): Pax genes and eye organogenesis. Curr Opin

Genet Dev 12:430.

Provis JM (2001): Development of the primate retinal vasculature. Prog Retin Eye Res 20:799.

Reza HM, Yasuda K (2004): Lens differentiation and crystallin regulation: a chick model. Int J Dev Biol 48:805.

Rutledge JC (1997): Developmental toxicity induced during early stages of mammalian embryogenesis. Mutat Res 12:113.

Sengpiel F, Kind PC (2002): The role of activity in development of the visual system. Curr Biol 12:R818.

Spencer WH (1996): Ophthalmic Pathology, 4th ed. Saunders, Philadelphia. Stromland K, et al. (1991): Ocular teratology. Surv Ophthalmol 35:429. Zieske JD (2004): Corneal development associated with eyelid opening.

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THERAPEUTIC FORMULATIONS

Although topical application of solutions, suspensions, and ointments is most common in ocular medicine, parenteral methods of administration via a systemic (i.e., intravenous, intramuscular, subcutaneous) or local (i.e., subconjunctival, intraorbital, intracameral, intravitreous) route are also used. Drugs for ocular administration are prepared in various ways. The topical use of powders for ocular treatment is detrimental to the eye and outmoded. Solutions, suspensions, and ointments for topical application must have physical characteristics within a relative narrow range to be well tolerated. Of these the most important characteristics are tonicity and pH. These parameters must also be considered by compounding pharmacists when formulating drugs for topical ophthalmic use.

Ophthalmic preparations must be sterile, especially if they enter the interior of the eye. Bacterial filtering and the addition of preservatives such as benzalkonium chloride are used to limit contamination of multidose containers. However, these preservatives are also toxic to mammalian cells. This fact has a number of important clinical implications:

•Topical drug use is not benign and should always be limited to the lowest effective concentration, frequency, and duration.

•Drugs designed for topical use should not be used intraocularly or injected, especially subconjunctivally.

•Preservatives in ophthalmic drugs and diagnostic agents may interfere with diagnostic attempts to isolate and grow microbes from the ocular surface.

Although topical application of drugs provides excellent drug concentrations at the ocular surface, there are two critical barriers to penetration of drugs into the eye. These are the blood-ocular barrier (which, like the blood-brain barrier, is impermeable to most drugs unless there is significant intraocular inflammation) and the cornea (which becomes more permeable when ulcerated).

ROUTES OF ADMINISTRATION

The main factors governing choice of the route of administration are as follows:

•Inherent properties of the drug

•Site of desired action (surface or intraocular structures)

•Frequency of administration possible

•Drug concentration required at target tissue

•Vascularity of the target tissue

Some drugs, because of their properties, are restricted as to the routes by which they can be given. For example, polymyxin B cannot be given systemically because of nephrotoxicity or by subconjunctival injection because of local irritation. Drugs required in high concentration in the cornea or conjunctiva are usually administered by frequent topical application or subconjunctival injection. If high concentrations are required in the anterior uveal tract (i.e., iris or ciliary body), subconjunctival injection, systemic administration, or frequent topical application of drugs that will pass through the intact cornea are used. Drugs that do not pass through the blood-ocular barrier still reach high concentrations in the highly vascular anterior uvea (iris and ciliary body), posterior uvea (choroid), and sclera. With inflammation the blood-ocular barrier may be reduced, and drugs that cannot normally enter the aqueous or vitreous humor may do so. If high concentrations are required within orbital tissues, systemic administration is usually used. Choice of route is summarized in Figure 3-1.

The cornea may be considered a trilaminar (lipid-water- lipid) “sandwich,” in which the epithelium and endothelium are relatively lipophilic and hydrophobic, whereas the stroma is relatively hydrophilic and lipophobic. Lipid-soluble drugs (e.g., chloramphenicol) penetrate more readily, whereas electrolytes and water-soluble drugs (e.g., neomycin, bacitracin, and penicillin) penetrate poorly if at all after topical application. The lipophilic properties of the epithelium may be partially bypassed by subconjunctival injection, provided that other properties of the drug are suitable for administration by this route.

Higher or more prolonged drug concentrations and therapeutic effects may be achieved with the following approaches:

•Increasing drug concentration in the topical preparation; for example, 1% prednisolone suspension results in higher intraocular concentrations than does 0.5% suspension (Figure 3-2).

•Increasing the frequency of application; for example, topical administration every 10 minutes for an hour results in higher concentrations than does a single application.

•Slowing absorption. Drugs released over a long period can be used to maintain drug concentrations. This is one mechanism whereby subconjunctival administration leads to higher topical concentrations of drug because of delayed release (“leakage”) of drug back along the injection tract. Penetration of topically administered drugs can also be enhanced through the use of preparations that maintain longer contact with the eye before being washed away by the tears (e.g., ointments, suspensions, or more viscous solutions).

•Facilitation of passage of drug between epithelial cells by limited and controlled damage of the intercellular adhesions of the epithelium with a surface-active preservative such as benzalkonium chloride (an additive in some drugs).

Fludrocortisone 0.1%

Cortisone 2.5%

Hydrocortisone 2.5%

Prednisolone 0.5%

Dexamethasone 0.1%

Prednisolone 1.0%

FIGURE 3-2. Relative antiinflammatory action of various corticosteroid preparations. Note that prednisolone (1.0%) and dexamethasone are relatively more potent than hydrocortisone. (Modified from Havener WH [1994]: Ocular Pharmacology, 6th ed. Mosby, St. Louis.)

C

D

Solutions and Suspensions (“Drops”)

Ophthalmic solutions and suspensions (or “drops”) are commonly used for topical treatment of ocular disease. They are usually easily instilled in dogs and cats but not in large animals. The correct method for instilling eyedrops is shown in Figure 3-3. Drops permit the delivered dose to be controlled and varied easily, and they are alleged to interfere less with repair of corneal epithelium than ointments, although this last feature is unlikely to be clinically significant. Drops are quickly diluted and eliminated from the eye by tears, so greater frequency of application or drug concentration may be required, especially with increased lacrimation. It is important to note that systemic absorption of drugs from the conjunctival sac after topical application is rapid and may result in notable blood concentrations. This may be of clinical significance with use of phenylephrine (producing systemic hypertension) and long-term corticosteroid use (inducing iatrogenic hyperadrenocorticism).

FIGURE 3-3. Correct method of instilling an eyedrop. The lower eyelid is held open with the hand being used to restrain the patient’s head. The upper eyelid is retracted with the hand holding the medication. The medication container is held 1 to 2 cm from the eye, and a single drop is instilled. Care must be taken to avoid the bottle touching the eye because this may injure the ocular surface or cause contamination of the drug remaining in the bottle.

Continuous or Intermittent Ocular Surface Lavage Systems

With frequent treatment or in horses with painful eyes, a lavage system allows medications to be conveniently, safely, and frequently delivered into the conjunctival sac. Originally, such systems were placed within the nasolacrimal duct and medications were instilled in a retrograde fashion. More recently subpalpebral lavage systems have been described that are simply placed and avoid nasal irritation and risk of dislodgement. A two-hole technique through the skin of the upper eyelid has now been replaced by single-hole systems, owing to the commercial availability of lavage systems with footplates to prevent inadvertent removal. The original one-hole system was placed in the central upper lid but is associated with a relatively high risk of complications, most notably corneal ulceration due to rubbing of the footplate on the cornea. Placement of the subpalpebral lavage system in the ventromedial conjunctival fornix may be preferred because of the natural corneal protection provided by the third eyelid at that point (Figure 3-4).

Subpalpebral lavage systems placed in the medial aspect of the lower lid are associated with less common and less severe ocular complications than those placed centrally and dorsally, even when left in place and used by owners for up to 55 days after discharge from hospital. The lavage tube leads back to the shoulder, where it is secured at the mane and where drugs can be administered with less risk of injury to the eye or the operator. Drugs are injected into the tube and either slowly propelled to the eye with a gently administered bolus of air from a syringe or continuously propelled by a gravity-fed bottle or small mechanical infusion pump connected to the tube. This method of therapy is usually reserved for horses with severe corneal or uveal disease. A protective eyecup can be applied over the lavage tube for protection of the eye and apparatus. Ointments (and some more viscous suspensions) cannot be applied through lavage systems.

Ointments

In horses the orbicularis oculi muscle is very powerful, and it is impossible to tilt the head to allow a drop of solution to

enter without contaminating the bottle. Ointments are preferred in such patients. Ointments also allow longer contact between the drug and surface tissues. Finally, less drug enters the nasolacrimal apparatus. Therefore ointments achieve higher tissue concentrations than solutions or suspensions do. A soothing effect occurs on instillation, they are a more stable medium for labile antibiotics and drugs, and they also provide physical lubrication and protect against desiccation better than solutions do. However, because oily ointment bases cause severe intraocular inflammation, and because application of ointments may result in ocular trauma from the tube itself, ointments are not recommended when globe perforation has occurred or is likely. Because they make tissue handling difficult and cause granulomatous inflammation if they penetrate ocular surface structures, ointments should also not be used before ocular or adnexal surgery. Finally, owners tend to overmedicate when using ointments, resulting in loss of medication, higher cost, and lower compliance with treatment regimens. As little as 0.5 cm of ointment from a fine nozzle is sufficient to medicate an eye.

Subconjunctival, Subtenons, and Retrobulbar Injection

Subconjunctival injection permits a portion of the administered drug to bypass the barrier of the corneal epithelium and penetrate transsclerally. However, a notable proportion of the injected drug leaks back out the injection tract and is absorbed as if it had been administered topically. Subconjunctival administration is used to facilitate high drug concentrations in anterior regions of the eye, whereas deeper injections beneath Tenon’s capsule allow greater diffusion of drugs through the sclera and into the eye. Mydriatics (for pupillary dilation), antibiotics, and corticosteroids are the main groups of drugs administered by this route. Some irritating drugs (e.g., polymyxin B) or any topical drug containing a preservative cannot be given subconjunctivally. Drugs with potent systemic sympathomimetic or vasopressor effects also should not be given in this manner.

In cooperative patients, subconjunctival injections can be given using topical anesthesia only. Handheld lid retractors may be helpful in all species (Figure 3-5). For horses and cattle, one should also consider tranquilization, appropriate restraint (a twitch for horses and nose grips for cattle), and an

A

auriculopalpebral nerve block to produce akinesia of the upper lid (see Chapter 5). A few drops of topical ophthalmic anesthetic (e.g., proparacaine) are instilled into the conjunctival sac. Conjunctival anesthesia is facilitated by a cotton-tipped applicator soaked in topical anesthesia and placed against the conjunctiva at the planned injection site for about 30 seconds. The solution for subconjunctival injection then is administered through a 25to 27-gauge needle with a 1-mL tuberculin or insulin syringe under the bulbar conjunctiva as close as possible to the lesion being treated (Figure 3-6). Injection under the palpebral conjunctiva is not effective. The needle is rotated on withdrawal to limit leakage through the needle tract. Up to 1 mL of drug can be given beneath the bulbar conjunctiva, but most injections do not exceed 0.5 mL. Slight hemorrhage into the injection site occasionally occurs but is absorbed within 7 to 10 days. Injections of depot preparations should be avoided at this site because they often lead to granuloma formation.

Supplies for subconjunctival injection are topical anesthetic, a cotton-tipped applicator, a 1-mL syringe (tuberculin or insulin), a 25to 27-gauge needle, and solution for injection.

Retrobulbar injection is used rarely and only for treatment of disease processes in the orbit or posterior half of the globe. These areas can usually be treated adequately with safer and simpler systemic routes of treatment. Therefore this route of therapy is now generally limited to the injection of local anesthetic into the muscle cone behind the globe for removal of the bovine eye.

Systemic Drug Administration

Although there are rare exceptions, systemically administered drugs should be considered to reach only the vascular tissues of the eye and surrounding structures—that is, not the cornea, the lens, or (in the presence of an intact blood-ocular barrier) the aqueous or vitreous humor. This knowledge may be used to the clinician’s advantage. For example, systemic administration of a corticosteroid for control of uveitis in the presence of corneal ulceration is safe and effective, because the target tissue (the uvea) is vascular, but the drug will not reach the avascular cornea in quantities sufficient to retard healing. Equally, the systemic administration of an antibiotic for treatment of

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