Canine corneal diseases: Treatment for transparency greater than the federal stimulus (Proceedings)

Corneal pathologic responses

The normal cornea is clear, and any alteration in clarity signifies pathology. Pathologic changes included corneal vessels, edema, pigment, lipid or calcium deposits, inflammatory cell infiltrates, destruction from degradative enzymes, and scarring. Such changes are usually non-specific and incited by numerous causes. Pathologic responses can occur singularly, but more often several occur simultaneously. Because corneal pathologic responses are usually secondary rather than primary, resolution is best achieved by identification and treatment of the primary cause.

Chronic superficial keratitis

Chronic superficial keratitis (or pannus) is an immune-mediated keratitis with genetic and environmental influencing factors. High altitude and ultraviolet radiation are the greatest environmental risk factors, and the most severe cases in this country occur in states such as Utah and Colorado. There is an obvious breed predisposition for German Shepherds and Shepherd crosses, but it can occur in any breed. It is also common in the Greyhound. It usually begins as a bilateral pink or red inflammatory lesion of the inferotemporal cornea and is often symmetrical. However, it can begin in other corneal quadrants and be asymmetrical. Histologically, the corneal infiltrate is characterized by plasma cells, lymphocytes, and blood vessels. With progression, the entire cornea can be affected and result in markedly diminished vision or blindness. Corneal pigment and fibrosis are prominent features in chronic cases. The nictitans can be involved simultaneously or exclusively (e.g., atypical pannus or plasmoma). Age of onset is usually 3-5 years but may occur at anytime. Pannus can be more difficult to control in dogs affected at a young age. Diagnosis is based on clinical appearance, breed predilection, and corneal or conjunctival cytology. Cytology usually reveals a preponderance of lymphocytes and plasma cells.

Like most immune-mediated diseases, pannus is a disease to be controlled rather than cured. Topical corticosteroid, cyclosporine, or tacrolimus are the primary treatments. The preferred steroid preparations are those with 1% prednisolone acetate or 0.1% dexamethasone. The required frequency of administration varies with the time of year and severity of pannus but is usually 2-4 times daily. Subconjunctival steroids can be administered as an adjunct to topical treatment, for refractory cases, or for dogs difficult to treat. Triamcinalone, methylprednisolone, and betamethasone are similarly effective, but conjunctival granuloma formation may be less likely to occur after betamethasone injection. Topically applied cyclosporine in concentrations of 0.2, 1 or 2%, or tacrolimus in concentrations of 0.02 or 0.03%, are also effective treatments. Some pannus cases are effectively controlled with cyclosporine or tacrolimus alone. In other cases, their use allows the steroid treatment to be reduced, thereby minimizing undesirable side effects. Treatments can often be reduced during the winter months but must be increased again during the summer months. Beta-irradiation and lamellar keratectomy are additional treatment options, but they are no longer commonly employed. Plasma cells and lymphocytes are particularly sensitive to beta-irradiation, and radiation is an effective treatment for difficult cases. However, stringent licensing requirements for the Strontium-90 probe have made irradiation an impractical treatment.

Scleritis/episcleritis

This is an immune-mediated condition that occurs as a nodular to diffuse inflammation of the sclera or episclera. It can be unilateral or bilateral. Often only one quadrant is affected, and because of the nodular appearance, scleritis can be mistaken for a neoplasm. However, scleral neoplasms other than limbal melanoma are rare. There is a breed predilection for the Cocker Spaniel and Airedale. The condition can be severe in the Airedale where concurrent uveitis is common (i.e., sclerouveitis). Lymphocytes, plasma cells, and histiocytes are typical histologic features. The adjacent cornea is usually affected with a variable degree of vessels, inflammatory cell infiltrates, and secondary lipid degeneration evident. Deep necrotizing scleritis is rare but can cause serious intraocular disease (e.g., retinal detachment). Diagnosis is by clinical appearance. Biopsy can be performed but is rarely necessary. Immune function tests (e.g., ANA, Coomb's, etc.) are often negative and of little benefit. Treatment usually involves a combination of topical and subconjunctival steroids or systemic treatment. Effective systemic treatments include prednisone, azathioprine, and combination treatment with tetracycline and niacinamide.

Oral or topical cyclosporine may be effective for some cases. Long-term treatment is likely to be required.

Pigmentary keratitis

Pigmentation of the corneal epithelium or stroma is called pigmentary keratitis (also called corneal melanosis or corneal pigmentation). Several conditions can contribute to corneal pigment including irritation from adnexal hairs (e.g., nasal trichiasis), redundant facial folds, dry eye, or lagophthalmos. Dry eye is probably the most common cause of corneal pigment in most breeds (except in the Pug). Pigment can occur subsequent to healing of an ulcer or in association with inflammatory conditions such as pannus. As a distinct or primary clinical entity, it occurs most often in the Pug. In this breed, contributing factors may include breed-related exophthalmos and corneal exposure, nasal lower lid entropion, and nasal canthal trichiasis. However, the greatest single factor is probably genetics because other breeds with similar conformation have far less pigment (e.g., the Bulldog, Pekingese, Shih Tzu, etc.). Nasal canthoplasty surgery (or permanent medial tarsorrhaphy) is most often advocated to slow or reduce progression of corneal pigment in the Pug. The advantages of this procedure include greater protection to the eye by reducing the palpebral fissure, elimination of nasal trichiasis hairs, and correction of nasal canthal entropion.

In Pugs, a combination of surgery and topical treatment is usually appropriate. Topical treatments that may slow or reduce corneal pigment include cyclosporine, tacrolimus, and corticosteroid. There is no evidence that cyclosporine is more effective than tacrolimus, or vice versa, so select the one best tolerated by the patient. Judiciously applied steroids can be of benefit, but they should always be used in a brachycephalic breed because of their propensity for corneal ulcers. Beta-irradiation or lamellar keratectomy may be effective treatments but are usually reserved for patients where pigment has progressed to the point of substantial visual impairment.

Corneal endothelial dystrophy

This condition is caused by a defective corneal endothelium and results in excessive corneal edema, thereby imparting a bluish-grey haze to the cornea. The primary differential diagnosis for edema is a corneal ulcer, uveitis, or glaucoma, each of which is usually easily distinguished from this condition. Endothelial dystrophy is slowly progressive, typically beginning in the lateral cornea and progressing to involve the entire cornea of middle-aged or older dogs. There is breed predilection for the Boston terrier and Chihuahua, but it can be seen sporadically in just about any dog breed. It is non-painful in the early stages. Advanced endothelial dystrophy will cause fluid pockets to form in the cornea (i.e., bullae or bullous keratopathy), ulcerative keratitis, and pain. Medical therapy is palliative with a hyperosmotic 5% sodium chloride ointment or suspension (Muro-128) used BID-QID to minimize edema. However, do not expect dramatic clearing of the cornea. Topical antibiotics or atropine are indicated if the cornea is ulcerated. Conjunctival hyperemia can be pronounced in some affected dogs, and the cause is not clear. If the eyes are especially irritated and there is no ulcer, topical steroids can be used cautiously. Topical NSAIDs (e.g., flurbiprofen) are sometimes of benefit. Thermal cautery (or thermokeratoplasty) may be beneficial in advanced cases where recurrent ulceration is a problem. This procedure will not clear the cornea substantially but results in enough scarring to prevent progressive edema and the pain associated with recurrent ulcers. The technique involves making multiple superficial corneal stromal burns using a disposable ophthalmic cautery unit or carbon dioxide laser. Surgical discretion is advised because the cornea can "melt like butter" under the heat of the cautery unit or laser. Penetrating keratoplasty (or corneal transplant) can be performed in selected instances.

Lipid or calcium keratopathy

Lipid or calcium corneal deposits may appear similar but have different causes, and absolute clinical distinction is not always possible. Nevertheless, three conditions are generally recognized: corneal dystrophy, corneal degeneration, and arcus lipoides corneae. The term corneal dystrophy refers to an inherited, bilateral, and often symmetric corneal lipidosis, although involvement of one eye may precede the other. Lipid corneal dystrophy occurs in a variety of dog breeds including the Siberian Husky, Samoyed, Cocker Spaniel, and Beagle. Clinically, the lipid deposits may impart a nearly imperceptible crystalline haze to the central or paracentral cornea, or the affected cornea may be opaque. The lipid is typically subepithelial or stromal and includes cholesterol, neutral fats, and phospholipids. There is no associated systemic disease. The cornea is usually non-ulcerated and there is an absence of inflammation or vascularization. Seldom does corneal dystrophy cause any significant visual impairment, nor does it cause any discomfort to the dog. For these reasons, specific treatment is not usually required. When treatment is desired, lamellar keratectomy is usually effective in removing the lipid deposits, however, the condition may recur. Corneal degeneration refers to lipid or calcium deposits, or both, in the corneal epithelium or stroma secondary to pre-existing ocular disease. Prior disease may include corneal ulceration, uveitis, or phthisis bulbi. In contrast to corneal dystrophy, corneal degeneration is often unilateral. The degenerative area of cornea is often quite opaque, roughened, and there is frequently disruption of the epithelium. This often causes discomfort to the animal. Concurrent inflammation, vascularization, and pigmentation are common. Lamellar keratectomy is the preferred treatment if the animal is in pain or visually impaired (and the eye worth saving), but the condition may recur. In some instances, a topically applied chelating agent (e.g., 0.4 to 1.38% EDTA solution) may be beneficial in dissolving calcium deposits when used either alone or in combination with keratectomy. A lipid corneal degeneration can occur following long-term topical corticosteroid treatments, such as that used after cataract surgery, but this type of degeneration is seldom problematic. The degeneration may regress somewhat following discontinuation of therapy. Lipid deposits that occur in the peripheral cornea in association with systemic hyperlipidemia are called arcus lipoides corneae. Clinically, the lipid causes a ring of opacity in the peripheral cornea. Although the condition can occur in any breed, a predisposition for German Shepherds with hypothyroidism is suggested. Arcus lipoides cornea is typically bilateral, and there may be mild inflammation and vascularization. Treatment is directed toward resolution of the primary disease condition. For most dogs with lipid or calcific keratopathy, I will usually obtain a fasted blood sample to evaluate cholesterol, triglycerides, and thyroid function. If fasting hyperlipidemia is noted, then the primary cause should be sought and treated. If blood work is normal, then dietary management may lessen the deposits or slow their progression.

Punctate keratitis

This is a relatively uncommon condition for which the Dachshund appears predisposed. Punctate keratitis appears to be immune-mediated, and this is the one instance of corneal ulceration where topical steroids are indicated. Affected eyes usually have multifocal punctate corneal opacities that retain fluorescein stain, and one or both eyes can be affected. Topical cyclosporine drops or ointment may be effective treatments, but more consistent results are usually obtained with topical steroid.

Sheltie corneal dystrophy

This condition has an obvious breed-predilection for the Sheltie, and the cause is unclear. Affected dogs have multifocal circular opacities of the cornea, many of which may retain fluorescein stain. Secondary lipid degeneration may occur. It can appear very similar to immune-mediated punctate keratitis, and may respond similarly to treatment. However, topical steroid should be used cautiously in these dogs, as their response to steroid is less predictable than in immune-mediated punctate keratitis. Affected eyes may have marginal tear production and reduced tear film breakup times, but overt dry eye is not a feature of this disease.

Corneal neoplasms

Tumors of the cornea (or sclera) occur infrequently. Corneal dermoid and limbal (epibulbar) melanoma are most common. Dermoids are benign congenital tumors that occur most often at the temporal cornea. They can usually be removed in their entirety by lamellar keratectomy. Limbal melanomas can have malignant histologic features, but they behave almost invariably in a benign manner. They tend to be slow growing but if ignored can become large enough to destroy the globe. As the name implies, they typically arise at the corneoscleral junction (limbus). Surgery will markedly slow progression of the tumor and may even be curative. However, complete excision is usually not possible without penetration of the globe, so there is no consensus as to the most effective treatment. Surgical options include full-thickness excision followed by a grafting procedure (i.e., with nictitans cartilage, etc), or partial excision followed by laser treatment or cryosurgery. The author has had good success with combined partial excision and cryosurgery.

Spontaneous chronic corneal epithelial defect (indolent ulcer or recurrent erosion)

This represents a specific unique type of corneal ulcer that is frustrating for veterinarians and clients alike. They are typically chronic, superficial, non-infected (except feline herpesvirus), and minimally to moderately painful. Most are characterized by redundant corneal epithelial edges and variable corneal vascularization. Indolent ulcers are believed to result form an abnormality of the corneal epithelial basement membrane. An indolent ulcer is suspected when a superficial ulcer persists for more than 7-10 days with no obvious cause or predisposing factor. Any breed can be affected, but most affected dogs are middle-aged or older. Appropriate topical treatment should include an antibiotic (e.g., neo-poly-bac or tobramycin) t.i.d. and 1% atropine once or twice daily for comfort. Topical hyperosmotic treatment with 5% sodium chloride ointment or drops may facilitate healing and reduce the risk of recurrence. Topical cyclosporine is helpful to reduce corneal vascular infiltrates and scarring. Corneal epithelial debridement and grid-keratotomy are most often recommended to facilitate healing. The intent of both procedures is to disrupt the abnormal basement membrane to allow for more effective attachment of epithelium to the underlying stroma. Epithelial debridement is performed after application of topical anesthetic and using a sterile dry cotton-tipped swab. One study estimated that approximately 40% of indolent ulcers heal after debridement alone, and this is probably an accurate percentage if the ulcer remains reasonably small after debridement. If the ulcer is large after debridement, then keratotomy is likely to be required.

Grid-keratotomy

This procedure is only intended for the treatment of superficial and non-infected ulcers and should never be performed on a deep corneal ulcer. Keratotomy is performed following debridement as described above. General anesthesia is recommended for fractious dogs or the first few times this technique is performed. In compliant animals, topical anesthesia and good restraint or sedation is all that is required. A 22 or 25 gauge needle is used to make superficial cuts or striations of the anterior stroma in a grid manner. This is done dragging the needle across the cornea at an approximately a 30-45 degree angle. Deep corneal penetration is to be avoided. The keratotomy should extend into normal cornea for 1-2 mm past the ulcer edges. The author prefers to use a tuberculin syringe as a handle with a 25 gauge needle attached. Medical treatments are continued as before. Oral anti-inflammatory and analgesics should be provided (e.g., a non-steroidal and tramadol), and the dog fitted with an Elizabethan collar. Most ulcers are healed within two weeks after grid-keratotomy.