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

immune-privileged site and may be protected by a blood-tear barrier. Disruption of this barrier may allow immune-mediated destruction of these tissues, resulting in KCS. Indeed, in some dogs with KCS circulating autoantibodies to the lacrimal glands, salivary glands, and gland of the third eyelid are present. As in humans, animals with KCS may also be affected with a variety of autoimmune or immune-mediated disorders, including Sjögren’s syndrome (dry mouth as well as eyes), systemic lupus erythematosus, pemphigus foliaceus, rheumatoid arthritis, hypothyroidism, diabetes mellitus, polymyositis and polyarthritis, atopy, glomerulonephritis, and ulcerative colitis.

Idiopathic. The majority of cases of idiopathic KCS may actually be immune-mediated, both in dogs and in the less commonly affected cat.

Orbital and Supraorbital Trauma. Trauma that either affects the glands directly or damages the nerves that innervate them may cause KCS. The disorder frequently accompanies traumatic proptosis. In horses KCS is rare, but the most common cause is regarded as trauma to the facial nerve.

Infectious. Canine distemper virus affects the lacrimal glands and glands of the third eyelid and may result in temporary or permanent dysfunction. KCS has also been associated with Leishmania infection and with chronic viral or bacterial conjunctivitis with fibrosis of the glands or their ducts. Feline herpesvirus may induce KCS through fibrosis of the lacrimal gland ductules.

Locoweed Poisoning. In cattle, sheep, and horses, locoweed poisoning can cause KCS.

Other Causes. Debilitated or dehydrated animals frequently have decreased tear production. Vitamin A deficiency rarely causes KCS in dogs, although it may do so somewhat more frequently in other species. Eosinophilic granulomatous dacryoadenitis, perhaps secondary to parasitic invasion into the lacrimal glands, has been reported as a cause in horses.

Congenital. Congenital acinar hypoplasia occurs in miniature breeds such as the pug, Chihuahua, and Yorkshire terrier. Cats with eyelid agenesis may also exhibit KCS due to absence of the glands or their ductules.

Senile Atrophy. Dogs 10 years or older are at increased risk for KCS due to senile atrophy of the lacrimal glands.

Radiation. The lacrimal gland and gland of the third eyelid, if in the field, may be damaged by radiation therapy.

Neurogenic. KCS may be seen in conjunction with loss of parasympathetic innervation of the lacrimal glands (cranial nerve [CN] VII) and in certain other neurogenic disorders, especially those involving the trigeminal nerve (CN V) and dysautonomia. Often, neurogenic KCS is unilateral and the nares on the affected side is also dry if the parasympathetic innervation is damaged proximal to the pterygopalatine ganglion.

KCS is a common and important ocular disease in dogs. It should be suspected whenever chronic conjunctivitis, keratitis, or ocular discharge is present.

Excision of the gland of the third eyelid is a common cause of KCS in dogs.

PATHOLOGIC CHANGES. A reduction in the aqueous portion of the tear film may result in compensatory conjunctival

cell hyperplasia and increased mucin production. Additionally, at least in the acute phase, the tear film becomes more hypertonic, leading to dehydration of the ocular surface epithelium (corneal and conjunctival), in turn resulting in edema, vacuolar degeneration, and generalized thinning of the corneal/ conjunctival epithelium. Corneal epithelial cells are more readily exfoliated by the greater friction associated with blinking and a roughened, keratinized conjunctival epithelium. Overt epithelial erosion or corneal ulceration may then occur, leading to substantial ocular pain as the trigeminal nerve endings in the cornea are exposed. Over time the conjunctiva becomes hyperemic and chemotic, and the epithelium undergoes squamous metaplasia and hyperkeratinization. The corneal epithelium also thickens and keratinizes. The resulting irregular epithelial surface may reduce the adhesion of the remaining tear film to the ocular surface, further worsening the condition. Inflammatory cells and blood vessels infiltrate the anterior corneal stroma, and pigment, lipid, and calcium may be secondarily deposited. When this occurs the cornea is typically less susceptible to ulceration, and if an ulcer develops it may be less painful because of loss of the superficial corneal sensation. Loss of antimicrobial substances normally suspended in the aqueous portion of the tear film (IgA, lysozyme) predisposes the dry eye to secondary bacterial and sometimes fungal infections. Not only may the bacteria lead to corneal malacia and perforation but the increased protease and inflammatory debris present within the remaining tear film may also raise the risk of corneal melting and perforation. A dry eye should be regarded not only as an immunocompromised eye but also as a nutritionally deficient one because the precorneal tear film supplies the anterior cornea with a significant portion of its metabolic needs.

BREED PREDISPOSITION. KCS occurs more commonly in the American cocker spaniel, bloodhound, Boston terrier, Cavalier King Charles spaniel, English bulldog, English springer spaniel, Lhasa apso, miniature schnauzer, Pekingese, poodle, pug, Samoyed, shih tzu, West Highland white terrier, and Yorkshire terrier.

CLINICAL SIGNS. The signs of KCS depend on whether the condition is bilateral or unilateral, acute or chronic, and temporary or permanent (Figures 9-19 to 9-21).

Mucoid and Mucopurulent Discharge. A thick, often ropy ocular discharge that clings to the ocular surface is the most consistent clinical sign of KCS. The discharge may be the result of increased mucin production by the conjunctival goblet cells and/or a reduction in the rinsing function of the tear film. The purulent component of the discharge may be sterile and the

Corneal vascularization

Lusterless cornea

Pigmentation

Ulceration

Dry, sticky, mucopurulent discharge

Dry ipsilateral nostril

Figure 9-19. Clinical signs of keratoconjunctivitis sicca.

Figure 9-20. Mild keratoconjunctivitis sicca in a dog with a history of intermittent conjunctival hyperemia and discharge. At this stage tear production may wax and wane, and it is easy to misdiagnose the condition as intermittent conjunctivitis presumably of bacterial or allergic origin.

Figure 9-21. Severe keratoconjunctivitis sicca in an American cocker spaniel. Note the thick mucopurulent discharge that clings to the cornea, the hyperemia conjunctiva, and corneal roughening and pigmentation.

result of inflammatory cell infiltrate into the conjunctiva or cornea, or it may be septic if secondary bacterial infection has occurred. Dried discharge is often present on the eyelids. The conjunctiva is usually hyperemic, thickened, and chemotic.

Blepharospasm. Variable severity of blepharospasm and protrusion of the third eyelid (presumably from frictional irritation as the lids move over a dryer ocular surface) are common. The level of pain depends on the amount of ocular surface sensitivity remaining.

Corneal Ulceration. In severe or acute cases the corneal epithelium is lost, especially centrally. Mucopurulent material or malacic corneal stroma may adhere to the ulcer bed. Corneal perforation and endophthalmitis may occur.

Corneal Vascularization and Pigmentation. Superficial and deep corneal vascularization and pigmentation often occur in chronic KCS. These changes are common causes of vision loss in this disorder.

Dry, Lusterless Cornea. The dry appearance of the cornea due to lack of the precorneal tear film is characteristic of KCS but occurs in only 25% of dogs with the disorder.

Dry Ipsilateral Nostril. The nares and nostril may also be dry on the affected side, especially in neurogenic KCS. This sign is thought to be due to impaired innervation of the lateral nasal gland in addition to the lacrimal glands.

Chronic Staphylococcal Blepharitis. Chronic infection of the eyelids and the tarsal glands, sometimes with hypersensitivity, may occur. Deficiency of the lipid layer of the tear film may accompany deficiencies of the aqueous and mucin layers.

Intermittent KCS is a common clinical entity and often can be diagnosed only with repeated performance of the STT. Unilateral cases of KCS may be more likely to be intermittent in nature than bilateral cases. Many patients show fluctuations in STT values above and below the normal lower limit of 10 mm/min, with clinical signs being more common either in the winter when humidity in the home is low or at hot, dry times of the year when evaporation of the tear film is the greatest. In brachycephalic breeds intermittent instances of KCS may result in ulceration. KCS should be suspected as a cause of the ulcer if the cornea is ulcerated and the STT value is less than 10 to perhaps 15 mm/min, because the normal response of the eye to ulceration should be to increase tear production above normal.

DIAGNOSIS. The diagnosis of KCS is suggested by the history (drug administration, “cherry eye” excision, repeated bouts of conjunctivitis that recur when topical medication is discontinued), clinical signs, and STT values. STT values less than 10 mm/min are suspicious for KCS, especially in brachycephalic breeds of dogs or in patients that should have epiphora (corneal erosion, conjunctivitis, etc.). Rose bengal staining may also be of value. Rose bengal stains conjunctival cells and mucus a bright rose red when devitalized by drying. The clinician should consider a complete hematologic and serum chemistry profile and other diagnostic tests to rule out other concurrent disorders or immune-related diseases that have been associated with KCS, including diabetes mellitus, hypothyroidism, polyarthritis and polymyositis, rheumatoid arthritis, and immune-mediated skin disorders.

NATURAL COURSE OF THE DISEASE. KCS caused by drugs, systemic diseases, and orbital and supraorbital trauma may resolve spontaneously in 45 to 60 days, but many patients do not recover. The majority of cases of idiopathic KCS do not improve without treatment. Patients with untreated, or undertreated, KCS are at substantial risk for vision loss.

Failure by owners to apply treatment adequately and consistently is a common cause of poor therapeutic results in KCS. The importance, aims, cost, and alternatives for therapy must be discussed with the owner at the start and reinforced throughout therapy.

TREATMENT. Initial therapy is medical, and in the majority of patients consistent medical therapy adequately controls the disease. In select cases surgery may be of benefit. In general, when multiple medications are being given to the same eye, it is best to space the applications out as evenly as possible. If such spacing is difficult, or impossible, solutions and suspensions should be given no closer than 5 minutes apart and ointments should be given no closer than 30 minutes apart. Given the current range of treatment options, poor owner compliance or low patient acceptance of therapy is the primary cause of visual impairment in KCS.

Medical Therapy. All medications should be applied to an eye that is as free of discharge and as clean as possible to ensure

adequate contact of the preparation with the target tissue. Application of any medication to a dry eye filled with debris and caked with discharge is almost invariably ineffective. Cleaning of the eyes and periocular tissue is usually best accomplished with a sterile eye wash and gentle wiping of the eyes with soft gauze or tissue. The aims of medical therapy are as follows.

Stimulate Natural Tear Production. Topical cyclosporine forms the cornerstone of KCS therapy. Available preparations include 0.2% ointment, which is approved by the U.S. Food and Drug Administration (FDA) for use in dogs, and 1% or 2% compounded formulations in an olive oil or corn oil base. All three formulations are clinically effective, although some patients may be more responsive to the 1% or 2% compounded formulations than to the commercially available ointment preparation. The compounded formulations, however, may be more irritating than the ointment in a small proportion (5% to 10%) of animals, and 2% cyclosporine may suppress systemic lymphocytes. There have been no reports of systemic adverse effects with topical cyclosporine.

The exact mechanism by which cyclosporine increases tear production is somewhat uncertain but involves immunomodulation by inhibition of helper T cells and by direct stimulation of tear production by binding to the cyclophilin receptor and thereby inhibiting prolactin, which in turn limits tear production. Additional effects of cyclosporine that are independent of its tear stimulatory effects are a reduction in corneal pigmentation and an improvement in conjunctival goblet cell mucin secretion.

A common regimen is to begin with topical cyclosporine ophthalmic ointment every 12 hours for a month and recheck tear production several hours after the medication has been administered. Topical cyclosporine therapy often requires a month or more before an effect may be seen (perhaps because of the time required to immunomodulate helper T cells and to allow the gland to regenerate), but once tear production does increase, the response to the drug is more immediate (minutes to hours after application). The latter response may be a function of a neurohormonal mechanism of action of the drug. If STT values are not substantially increased (> 10 mm/min), the same regimen may be continued for 2 more months or 1% or 2% compounded cyclosporine every 12 hours may be used for several months. During this time an STT, performed a few hours after cyclosporine has been applied to the eye, is performed monthly. If tear production still has not increased, 1% cyclosporine every 8 hours or topical tacrolimus every 12 hours may be tried. If tear production (STT value) consistently exceeds 20 mm/min (uncommon), tear stimulant therapy may be reduced to once a day and all the other medications may be discontinued.

Tacrolimus (formerly FK506) is a potent immunomodulator with a mechanism of action believed to be similar to cyclosporine A but with a reported 10to 100-fold higher potency. In one study, compounded 0.02% tacrolimus suspension applied every 12 hours was highly effective at improving tear production. All dogs that were controlled with cyclosporine A also could be controlled with tacrolimus, and in about one quarter of those dogs, tear production rose an additional 5 mm/min or more. Additionally, a significant number of dogs who did not experience increased tear production with cyclosporine did so with tacrolimus. In addition to increasing tear production, tacrolimus also reduced many of the other symptoms of KCS. Despite these promising results the potential toxic side effects of the drug and the potential carcinogenicity of the compound do indicate that further studies are required before the drug can be

determined to be safe for the animal as well as for the human who applies the medication. A related compound, pimecrolimus, also experimentally improved tear production in dogs treated with a 1% corn oil–based formulation three times a day, but its long-term safety is also unknown.

Pilocarpine, administered either topically or systemically, may be used in selected cases in an effort to stimulate tear production. In view of its mechanism of action, it would be expected to be most effective in patients with neurogenic KCS secondary to parasympathetic denervation, in which peripheral cholinergic receptors have undergone upregulation and are more sensitive to the effects of cholinergic stimulation than other cholinergically innervated tissues. Pilocarpine may be used topically in a dilute form in artificial tears (0.125% or 0.25%) given every 6 to 8 hours or orally by being mixed with the animal’s food. In the latter instance the initial dose applied to the food is 1 drop of 2% topical pilocarpine per 10 kg of body weight twice daily. The dose is increased in 1-drop increments every 2 to 3 days until signs of systemic toxicity develop (inappetence, hypersalivation, vomiting, diarrhea, bradycardia). Because the efficacy of this approach depends on a differential sensitivity of the lacrimal glands than other tissues (gastrointestinal, cardiac), the therapeutic window is quite narrow, and one needs to see subtle signs of toxicity in other tissues before concluding that the drug is ineffective. In my experience the drug is seldom effective in treating KCS, and its side effects (local ocular irritation, inappetence, vomiting/ diarrhea) may preclude its long-term use.

Other promising tear stimulants in dogs in the experimental setting are the use of 100 ML of nerve growth factor ointment every 12 hours and oral administration of low-dose interferon-A. The long-term safety and efficacy of these compounds remain to be elucidated.

Replacement of the Precorneal Tear Film. Wetting agents are second best to drugs, which increase natural tears. They do, however, play an important role in improving the ocular health of animals in which tear stimulant therapy does not raise tear production to adequate levels or while waiting for tear stimulant therapy to begin to work. There are many types of artificial tears, and in addition to a wetting agent, they contain varying amounts and types of preservatives. A preparation is initially selected on the basis of the tear function that needs replacement and the individual needs of the patient. If a particular brand of tear replacement therapy is effective but irritating, a related compound with a different or no preservative should be tried. Often a variety of agents are tried before the optimal formulation is identified for an individual patient.

Preparations with polyvinyl alcohol (common in many over- the-counter formulations) are relatively watery in consistency, resulting in a relatively short contact time and the need for frequent application. They are best selected when the goal is to keep the eye free of debris, and by themselves they are typically inadequate to treat a substantially dry eye. The addition of dextrans (e.g., Hypotears) results in a slightly more viscous material that better mimics natural mucins and should be considered if the goal is to replace the mucin layer. The addition of methylcellulose (e.g., Isopto Tears, Tears Naturale, GenTeal lubricating eyedrops, GenTeal gel, Refresh Celluvisc Tears) makes the solution more viscous, slows its evaporation rate, increases the corneal contact time, and also is beneficial if the goal is to replace the mucin layer. The greater viscosity of these agents also makes them good choices when the goal is to lubricate the eye, although they may result in more debris

around the eyelids. The addition of viscoelastic agents such as chondroitin sulfate and sodium hyaluronate (Hylashield) result in one of the longest contact times, but these compounds may not be readily available in the United States.

Ointments containing petrolatum, mineral oil, or lanolin (e.g., Duratears, Lacri-Lube, Puralube, Lubri-Tears) are very thick and have the longest contact time but are the least like natural tears. They are best used in animals with exposure keratitis expected to go long periods without treatment, just before bedtime, or in patients with lipid layer deficiencies. Although the long contact time makes it appealing to use these compounds in severely dry eyes, their viscous nature usually results in a thick “gummy” material that may be uncomfortable. Severely dry eyes typically respond better to less viscous compounds than the ointments.

Reduce Ocular Surface Inflammation. Topical cyclosporine or tacrolimus may have some efficacy at reducing ocular surface inflammation—even if they do not increase tear production. If these agents are inadequate, a short course (1 to 4 weeks) of topical 0.1% dexamethasone or 1% prednisolone acetate applied every 6 to 8 hours may be used to reduce corneal vascularization, pigmentation, and inflammation. Topical corticosteroids may also be useful in patients in which conjunctival swelling around the lacrimal ductules precludes tear secretion stimulated by cyclosporine or tacrolimus. Topical corticosteroids are usually not used long term, and it is mandatory to perform fluorescein staining of the cornea before their use to ensure absence of even minor corneal erosions or abrasions. In general these compounds should be used with extreme caution in acute KCS because of the risk of corneal ulceration or perforation. Alternatively a topical NSAID such as flurbiprofen could be used.

Control Secondary Infection. Because white blood cells may be present within the cornea/conjunctiva and on the ocular surface simply as a result of inflammation associated with drying, the presence of a purulent discharge does not necessarily indicate a secondary bacterial infection. Conjunctival cytology can be a useful guide in determining whether the discharge is sterile or septic and whether topical antibiotics are required. If bacterial overgrowth or secondary infection has occurred, topical antibiotics such as neomycin/bacitracin/polymyxin B may be used every 6 to 8 hours. If corneal ulceration has occurred, topical antibiotics should be applied more frequently and corneal cytology and culture/sensitivity testing should be considered (see Chapter 10 for details). Additionally, the response to therapy should be closely followed because ulcerative keratitis in patients with KCS often becomes malacic and corneal perforation is not uncommon. In general topical antibiotics are not typically required on a long-term basis, and their continual application typically results only in ocular irritation or resistant organisms.

Removal of Excess Mucus. Rinsing the eyes with sterile eye wash is often sufficient to remove excess mucus. Mucolytics may be used in selected patients with copious discharge that clings tenaciously to the ocular surface and eyelids. Although 5% acetylcysteine may be used as a mucolytic, its low pH may result in irritation, it has a shelf-life of only a few days once opened, and it is expensive. Nevertheless it may be useful, at least in the short term, in patients with unusually thick and tenacious discharge.

Owner noncompliance with frequent medication regimens is an important cause of treatment failure, especially when response to cyclosporine is poor.

Follow-up. Initial therapy typically consists of cleaning the eyes at least once daily with sterile eye wash, topical application of cyclosporine ophthalmic ointment every 12 hours, use of an artificial tear (selected on the basis of the most pressing need for replacement—cleaning, lubrication, or addressing exposure) every 2 to 4 hours, and topical application of antibiotics if bacterial overgrowth has occurred. If the conjunctiva is quite chemotic and the cornea is negative to fluorescein stain, topical corticosteroids or an NSAID may be considered. In select cases with copious discharge a mucolytic may also be used. A lubricating ointment is usually given at bedtime. The patient is examined at 1 month (ideally a few hours after receiving cyclosporine), and tear stimulant therapy is adjusted as described previously. Unless advised otherwise, many owners do not treat the pet on the day of the visit, thereby making it difficult for the clinician to assess the efficacy of cyclosporine therapy. If a corneal ulcer or erosion was present at the initial examination, the timing of the recheck appointment is dictated by the corneal defect and not by the KCS.

In many animals cyclosporine or tacrolimus may increase tear production to the extent that other medications may be reduced or eliminated. Even if tear production does not increase, therapy with cyclosporine and the other compounds often results in substantial clinical improvement and retention of vision. A higher proportion of dogs with an initial STT value above 2 mm/min show a beneficial response to cyclosporine than those with a reading below 2 mm/min. If the STT value is 0 at commencement of treatment, the chance of response to cyclosporine is less, although overall clinical response to the regimen may be good. Corneal pigmentation may be reduced in about 80% of affected dogs. In rare cases or in patients with intermittent KCS, cyclosporine may be discontinued and tear production remains at normal levels. Topical cyclosporine is ineffective in KCS secondary to distemper, trauma, or advanced glandular fibrosis and in many drug-induced forms of the disorder.

If severe ulceration is present, the above topical therapy, including cyclosporine, is used in addition to aggressive antibiotic therapy, and the eye is treated as described in Chapter 10. Some patients need immediate surgical therapy if corneal rupture is imminent, and such high-risk patients should be referred to an ophthalmologist.

A minimum of 3 to 6 months of medical therapy is desirable before surgical therapy for KCS is considered, because some dogs regain tear production during this time. If surgical treatment is performed too early, epiphora may result when tear production returns, requiring surgical reversal. By the end of 3 to 6 months, the owner has often decided in favor of either medical or surgical treatment. For long-term medical treatment, antibiotics, corticosteroids, and acetylcysteine may be reduced or deleted from the regimen. For cases that fail to respond with increased tear production or in animals that demonstrate sensitivity to cyclosporine or tacrolimus or for whose owners topical treatment is inconvenient, surgical therapy is a viable alternative.

Complications of KCS with medical therapy include vascularization, scarring, and pigmentation of the cornea to varying degrees. Surgical attempts to remove this opaque tissue by keratectomy have a low success rate, with postoperative return of the tissue in a high proportion of patients. Complications of such keratectomy include reduced tear flow, thought to be due to section of the corneal nerve and reduced reflex lacrimation, bacterial keratitis, predominantly with gram-positive

organisms, and delayed reepithelialization of the cornea. The best candidates for this procedure are patients with an excellent response to cyclosporine, STT values above 15 mm/min, absence of recent or current bacterial conjunctivitis, and minimal limbal or conjunctival pigment.

Surgical Therapy

Parotid Duct Transposition. The parotid duct conducts saliva from the parotid gland to an oral papilla near the carnassial tooth. In the transposition procedure the duct and papilla are mobilized and transferred to the conjunctival sac to provide substitute lubrication. The technique is technically demanding and requires precision and practice. Even if successful, it rarely eliminates the need to treat the eye topically.

Because of potential complications (occurring in 9% to 37% of cases, as reported by various authorities), parotid duct transposition should be undertaken only by a competent surgeon experienced in the technique and after medical treatment has been evaluated for at least 3 to 6 months.

Before this technique is performed, the teeth are cleaned, and if periodontal disease is present, systemic antibiotics are given for 14 days. Before surgical intervention, the clinician confirms function of the parotid gland and patency of the duct and eliminates the possibility of xerostomia by placing one or more drops of 1% atropine onto the oral mucosa and observing the papilla for secretion. In this circumstance, 1% atropine is used not for its parasympatholytic effects (which would reduce saliva production) but because it is very bitter tasting and acutely induces profuse salivation when administered via this route.

Under general anesthesia the oral cavity is cleaned and packed with gauze soaked in povidone-iodine solution. The lateral surface of the face is prepared for surgery, and the parotid papilla is cannulated with 2/0 nylon (colored) with a smooth blunt end (Figure 9-22). This cannula facilitates later identification and manipulation of the duct. Because of a rightangle bend in the duct as it enters the papilla, perseverance may be necessary to effect cannulation. Grasping the papilla and moving it rostrally reduces the bend and makes passage of the nylon easier.

Subcutaneous approaches (“closed procedures”) in which no facial skin incision is made have also been described. In this version the papilla and duct are dissected free via the oral cavity to the point near where the duct attaches to the gland. From there a subcutaneous tunnel is made by blunt dissection to the inferior-lateral conjunctival cul-de-sac, where the papilla is sutured in place. Extreme care must be taken not to twist or rotate the duct as it is being transposed.

Both the “open” and “closed” procedures are effective, and the decision as to which one to use is largely personal preference because both procedures have their proponents and detractors.

Postoperative Treatment. Until a regular supply of parotid secretions is established, cyclosporine, artificial tears, and topical

antibiotics are used several times a day. Small, regular amounts of food (e.g., a dry dog biscuit every hour or so at the owner’s convenience) and soft food are used to establish a continuous supply of secretion until skin sutures are removed at 10 days.

Operative and Postoperative Complications. Postoperative subcutaneous edema is common for the first few days and can be limited by careful suturing of the oral mucosal incision to prevent saliva from entering the wound.

The most severe intraoperative complication is severing the duct from the papilla, which results in scar formation and constriction around the junction with the conjunctiva. If the end of the duct is opened with an incision along both sides for 2 to 2.5 mm, a wider opening with less chance of constriction can be obtained. Careless or traumatic handling of the duct with instruments leads to cicatricial constriction and obstruction. Microsurgical resection and anastomosis of obstructions is possible but cannot be relied on to repair the results of poor surgical technique.

The most common postoperative complication is accumulations of whitish crystalline mineralized material from salivary secretions on the ocular surface and lid margins. These accumulations cannot be prevented and, if substantial, result in blepharoconjunctivitis and blepharospasm. They can be reduced by frequent applications of 1% to 2% ethylenediaminetetraacetic acid (EDTA) in artificial tears. Continued use of cyclosporine may be helpful because of its lubricant and antiinflammatory properties. Facial irritation from overproduction of saliva may occur, but ligation of the parotid duct is rarely necessary. After parotid duct transposition, the numbers of bacteria on the surface of the eye increase, with many uncommon organisms isolated. Usually these organisms are nonproblematic although they may contribute to blepharoconjunctivitis in some patients. If glandular function returns after transposition, epiphora can result. It may be prevented in the majority of patients by adequate medical evaluation before surgery is attempted. If epiphora should occur, ligation of the duct or re-transposition to the mouth is curative. Salivary flow can also be reduced by surgical reduction of the diameter of the parotid duct.

NEOPLASIA

Neoplasms of the lacrimal gland are rare in dogs and manifest as space-occupying lesions that can be removed by suitable orbital approaches (see Chapter 17). Lacrimal adenocarcinoma has a good prognosis if removed early, while still localized. Conjunctival neoplasms may invade the nasolacrimal duct and spread to the nasal cavity; likewise, neoplasms in the nasal cavity may invade the nasolacrimal duct. Space-occupying nasal lesions may obstruct the nasolacrimal duct, causing epiphora. Cryotherapy may be used near the lacrimal puncta and canaliculi without causing permanent obstruction.

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ANATOMY, PHYSIOLOGY, AND WOUND HEALING

Cornea

The outer, fibrous coat of the eye consists of the posterior, opaque sclera and the anterior, transparent cornea. The anteriormost sclera is covered by the translucent bulbar conjunctiva. The point at which the cornea, sclera, and bulbar conjunctiva merge is called the limbus. In domestic species the horizontal diameter of the cornea is greater than the vertical diameter. This difference is especially notable in the large herbivores. The corneal thickness varies among species and across regions of the cornea but is usually between 0.5 and 0.8 mm.

The cornea has the following four layers (Figure 10-1):

•Stratified epithelium and its basement membrane

•Collagenous stroma

•Descemet’s membrane (basement membrane of the endothelium)

•Endothelium

The corneal epithelium is stratified, squamous, and nonkeratinized. From deep to superficial it comprises the basement membrane, basal epithelial cells, wing cells, and squamous surface cells (Figure 10-2). Basal cells are attached to the basement membrane by hemidesmosomes. As basal cells divide, daughter cells are forced toward the surface, become flattened as wing cells, and gradually lose many of their organelles. Basal cells are replaced by stem cells at the limbus that are constantly undergoing mitosis and migrating centripetally. Surface squamous cells possess microvillous projections that anchor the deep mucin layer of the precorneal tear film. The corneal stroma, composed of keratocytes, collagen, and ground substance, constitutes 90% of the corneal thickness and lends rigidity to the globe. The parallel collagen fibrils form lamellae of interlacing sheets (Figure 10-3), with occasional interspersed keratocytes (which are modified fibroblasts), lymphocytes, macrophages, and neutrophils. The regular spacing of stromal collagen fibrils maintains corneal transparency and distinguishes corneal stroma from the collagen in scar tissue and sclera.

Descemet’s membrane is the basement membrane of the endothelium, lying between the posterior stroma and the endothelium (see Figures 10-1 and 10-4). Because it is continuously secreted by endothelial cells throughout life, this membrane thickens with age. It is very elastic but can break from globe stretching (buphthalmos), as seen with advanced glaucoma, or with penetrating injuries or ruptured ulcers. Descemet’s mem-

brane becomes exposed in ulcers in which there is complete stromal loss (descemetoceles). It does not stain with fluorescein and therefore appears as a dark, transparent, sometimes outwardly bulging structure in the center of a deep corneal ulcer or wound.

The endothelium is one cell layer thick and lies posterior to Descemet’s membrane, lining the anterior chamber. Its role is to pump ions from the stroma into the aqueous. The movement of water that follows these ions ensures that the corneal stroma remains relatively dehydrated. This function is a major contributor to corneal transparency. Endothelial cells in the adult animal are postmitotic and have a limited capacity to replicate in most species. With advancing age, endothelial cells are lost and the corneal stroma becomes thicker owing to subtle edema. The normal canine endothelial cell density in young dogs is approximately 2800 cells/mm2. Corneal decompensation and inability to remove water from the stroma occur when endothelial cell density falls below 500 to 800 cells/mm2. The endothelium may be prematurely lost or damaged because of genetic predisposition (endothelial dystrophy), trauma (exogenous and due to anterior lens luxation), intraocular or corneal surgery, intraocular inflammation (uveitis), or glaucoma. Such loss of corneal endothelium, beyond the ability of surrounding cells to compensate, usually causes permanent corneal edema and opacity.

The cornea is the most powerful optical refracting surface in the eye. This ability relies mainly on appropriate corneal curvature and transparency. Corneal transparency is maintained by numerous specialized anatomic and physiologic features. The following features keep the cornea transparent:

•Lack of blood vessels

•Relatively low cell density

•Lack of melanin (or other pigments)

•Maintenance of a relatively dehydrated state

•A smooth optical surface (provided by the precorneal tear film)

•A highly regular arrangement of stromal collagen fibrils

•Lack of keratinization

Factors that alter the collagen lattice or spacing of collagen fibrils, the optical surface, or the type of collagen all reduce corneal transparency (see Figure 10-3). Common examples are corneal edema, corneal scarring, loss of epithelium, alterations in the precorneal tear film, elevated intraocular pressure (IOP), damage to endothelium, formation of scar tissue, altered glycosaminoglycan content, melanosis, corneal vascularization, and infiltration of the stroma with white blood cells.

Because the cornea is avascular, oxygen and nutrients must be obtained and metabolites disposed of through alternate

A

B

C

D

FIGURE 10-1. Photomicrograph of the feline cornea. A, Epithelium; B, stroma; C, Descemet’s membrane; D, endothelium.

FIGURE 10-2. Drawing of the corneal epithelium comprising columnar basal cells (A), polyhedral wing cells (B), and nonkeratinized surface squamous epithelial cells (C). The basal cells are subtended by the epithelial basement membrane (D), stromal keratocytes (E), and collagenous stroma (F). Note also the extensive arrays of microplicae and microvilli at the corneal surface (G), which help retain the tear film. A sensory (trigeminal) nerve fiber (H) is shown penetrating the epithelium at its base, and a lymphocyte (I) can be seen migrating through the basal epithelium. (Modified from Hogan MJ, et al. [1971]: Histology of the Human Eye. Saunders, Philadelphia.)

routes (Figure 10-5). Such routes include the aqueous humor, the precorneal tear film and the atmosphere, and adjacent capillary beds in the sclera and bulbar and palpebral conjunctiva. The endothelium and posterior stroma receive most of their nutrients from the aqueous humor, but the tear film and atmospheric oxygen are the major sources for the anterior cornea.

Normal Corneal Healing

Each component of the cornea heals to a different degree, at a different rate, and via completely different mechanisms.

A

B

C

FIGURE 10-3. The corneal stroma. A, Collagen lamellae. Parallel collagen fibrils lie within a lamella and run the full length of the cornea. Successive lamellae run across the cornea at angles to one another. Fibroblasts are shown between the lamellae. B, Cross-sectional orientation of normal stromal collagen fibrils. Each of the fibrils is separated from its fellows by equal distances because of mucoproteins, glycoproteins, and other components of the ground substance. Maurice has explained the transparency of the cornea on the basis of this very exact equidistant separation, which results in the elimination of scattered light by destructive interference. C, Cross-sectional view of disoriented collagen fibrils, which scatter light and result in reduction of corneal transparency. The orderly position of the fibrils can be disturbed by edema, alterations in the ground substance, scar formation, or infiltration of the interlamellar spaces by cells or substances such as mineral and lipid. (Modified from Hogan MJ, et al. [1971]: Histology of the Human Eye. Saunders, Philadelphia.)

Corneal lamellae

Descemet’s membrane

Endothelium

Tight junction

Marginal folds

Microvilli

FIGURE 10-4. Inner cornea showing the deepest corneal lamellae, Descemet’s membrane, and the endothelium. The deeper stromal lamellae split, and some branches curve posteriorly to merge with Descemet’s membrane. Descemet’s membrane is seen in meridional and tangential planes. The endothelial cells are polygonal. Microvilli on the apical surface of the endothelial cells and marginal folds at the intercellular junctions protrude into the anterior chamber. Intercellular spaces near the anterior chamber are closed by a tight junction. (Modified from Hogan MJ, et al. [1971]: Histology of the Human Eye. Saunders, Philadelphia.)

An understanding of these differences will help the clinician better assess whether healing is progressing abnormally, take appropriate steps to halt delayed healing or clinical deterioration, and offer more accurate prognoses after ocular injury or disease.