John S. Sapienza, DVM, Diplomate, American College Of Veterinary Ophthalmologists
The cornea is composed of five basic layers: the precorneal tear film, the epithelium and its basement membrane, the stroma, Descemet's membrane, and the corneal endothelium.
The transparency of the cornea is based on the lack of blood vessels and cells, the lack of pigment, the control of corneal water content, and the smooth optical surface afforded by the precorneal tear film. The cornea can react to disease in several fashions: with edema, vascularization, scar formation, pigmentation, cellular infiltration, and the accumulation of abnormal substances.
Corneal ulcers can be divided into superficial and deep stromal ulcers. Superficial ulcers generally heal quickly and uneventfully. Topical broad-spectrum antibiotics such as BNP or chloramphenicol QID are advised in addition to topical atropine TID-QID, as well as a protective Elizabethan collar.
Generally, more aggressive therapy is necessary for deep corneal ulcers, desmetoceles, iris prolapses, and melting corneal ulcers (keratomalacia). Deep corneal ulcers (> 1/2 stromal depth) are best treated with surgical intervention; i.e., a conjunctival pedicle / island graft or a corneal graft. Third eyelid flaps do not generally provide the support for the weakened cornea.
Corneal lacerations are best to refer to the ophthalmic specialist as early as possible for prompt repair. If the iris is prolapsed and appears viable, replacement can be performed or the iris can be amputated if considered necrotic. The cornea is sutured with 7-0 to 10-0 suture, and the anterior chamber is reformed.
Keratomalacia, or the so-called " melting corneal ulcer, " is common in clinical practice. Prior to the instillation of any ophthalmic medication, the edge of the lesion is cultured with a sterile culture swab. Cytology is obtained at the leading edge of the lesion after the instillation of topical proparacaine. General guidelines for the appropriate treatment of melting ulcers include: fortified topical antibiotics (gentamicin, tobramycin, or ciprofloxacin every 1-2 hours), topical serum or plasma, subconjunctival gentamicin or tobramycin, topical atropine, systemic antibiotics, and often surgery; namely, a conjunctival graft to provide support, blood vessels and healing serum factors.
Thoughts to Consider
The depth of the ulcer. Deep ulcers need support in the form of corneal or conjunctival grafts. Third eyelid flap won't do the job. Deep corneal ulcers rarely improve with topical medications as the sole therapy. Many deep corneal ulcers proceed to corneal perforations without the proper surgical intervention and judicious, close monitoring.
Complicated, infected ulcers need intensive therapy. Initially, I recommend hourly drops!
Anti-collagenase activity needs to be addressed. Topical serum is readily available and works very well. You must be very aseptic when preparing the patient's serum, for a sample contaminated with bacteria can iatrogenically super-infect the lesion. Although many veterinarians commonly use acetylcysteine, experimental studies show that this product is not very efficacious. Anyway, it smells like rotten eggs.
Infected corneal ulcers need the " heavy guns " of antibiotics. Fortified solutions can be made by injecting intravenous antibiotic preparations into the ophthalmic grade antibiotic bottle.
Atropine is essential for cycloplegia.
Early surgical intervention is important. Many surgical techniques are available in order to save the globe and to restore good vision.
CORNEAL LESIONS OF THE DOG
Indolent ulcers are due to a defect in the basement membrane, the corneal "glue" if you will, which adheres the epithelium to the underlying corneal stroma. The diagnosis of indolent ulcers is rather straightforward. With the use of fluorescein stain, one can observe the stain to seemingly migrate under the edge of the epithelium (the so-called epithelial " lipping ") due to a detachment of the overlying epithelium to the underlying stroma. Therapeutic options focus on the re-enforcement or re-creation of this basement membrane, and to promote the adhesion of the epithelium to the underlying corneal stroma. Both medical and surgical options are available. Several topical ophthalmic treatments have been published for these cases of indolent ulcers and include: topical fibronectin, epithelial growth factor, serum, polysulfated glycoaminoglycans, aprotinin, and hyperosmotic agents. Certain ophthalmologists perform a complete superficial lamellar keratectomy as part of their initial therapy. Other ophthalmologists use topical ophthalmic grade cyanoacrylate over the debrided corneal bed to provoke the migration of healing corneal vessels. I prefer to perform, under topical anesthesia, epithelial debridement and multiple superficial keratotomies as the initial treatment. After topical debridement and keratotomies, I place a bandage soft contact lens on the patient's eye, and administer topical triple antibiotic solution and atropine solution. One must be very careful not to create too deep a keratotomy to the eye. Furthermore, keratotomies are contraindicated in cats with indolent ulcers, for the keratotomies may predispose the cat to the formation of a corneal sequestrum (focal corneal necrosis). An Elizabethan collar is always advised to minimize self-trauma to the eye. Ointments are not recommended, as they may inhibit corneal healing. Likewise, topical aminoglycosides (namely, gentamicin) are not advised due to their epitheliotoxicity. Indolent ulcers take usually 2-4 weeks to heal. In certain cases of indolent ulcers, especially in Boxers, the dogs heal with excessive vascularization to even frank granulation tissue formation. When the ulcer is healed, as evidenced by no fluorescein retention, a topical lubricant ointment is applied to improve the regularity and smoothness of the cornea. Topical corticosteroids are never prescribed by me to improve the vascularization. I prefer to allow time to heal the cornea, rather than risk another episode of corneal ulceration.
Keratoconjunctivitis Sicca: Dry Eye Syndrome
Keratoconjunctivitis sicca, or KCS, is one of the most frequent causes of corneal disease in the dog. Whenever one observes a canine patient with a mucoid or mucopurulent ocular discharge, dry-appearing cornea, or corneal pigmentation, the diagnosis of KCS must be entertained. Although less frequently diagnosed in the feline species, KCS does indeed affect the cat and is most commonly associated with herpesvirus infection (past or present). The clinical signs of KCS are varied, and can include a mucoid to mucopurulent ocular discharge, conjunctivitis, keratitis, dull-appearing cornea ("lack-luster cornea "), pigmentary keratitis, acute-forming corneal ulcers (even corneal ruptures with an iris prolapse), and blindness. The majority of causes of KCS in dogs are considered to be idiopathic, with an immune-mediated basis. KCS may or may not be associated with concurrent systemic illnesses such as diabetes mellitus, lupus, and hypothyroidism, A minority of KCS cases can be attributed to a specific cause such as secondary to canine distemper virus infection, idiosyncratic reaction to oral sulfonamides, reactions to other drugs, i.e., topical atropine or anesthetics (proparacaine, lidocaine, tetracaine), and recently noted secondary to etodolac (EtoGesic®), congenital hypoplasia or aplasia of the lacrimal glands, facial neuropathy, and removal of the third eyelid gland. Do not even think of removing the third eyelid gland in these cherry eye cases!!!
The diagnosis of KCS is relatively straightforward. A Schirmer tear test (STT) is left in the lower conjunctival fornix for one minute, and a reading of > 10 mm wetting per minute is considered normal, between 6-10 mm as suspicious for KCS, and <5 mm as diagnostic for dry eye. Rose Bengal staining of the eye can demonstrate early corneal or conjunctival lesions. Diffuse pigmentary keratitis may be seen in very chronic cases of KCS. NOTE: Do a STT on all cases of red eyes with a mucoid / mucopurulent ocular discharge.
The goals of KCS therapy are three-fold:
To substitute tears.
To stimulate tear production.
To treat any underlying infection.
Artificial tears (Refresh®, Celluvisc®, Hylashield®) can be used to substitute tears, but literally must be instilled every 30-60 minutes if used as sole therapy for dry eyes. This not only is impractical, but also not necessary for our patients. Use artificial tears as adjunctive therapy for KCS, not as the only therapeutic option for tear replacement.
Stimulation of tear production can be achieved by the use of pilocarpine (oral or topical therapy) and topical cyclosporine A therapy. A dilute (1/4 %) pilocarpine solution can be used as a topical drop or oral 2 % pilocarpine can be added to the food
(At 1 drop of a 2 % pilocarpine solution per 10 kg. body weight). Cyclosporine A (CSA) is the treatment of choice for KCS. One can use topical CSA every 12 hours as a 1-2 % solution (mixed in corn or mineral oil) or the commercially prepared 0.2 % ointment (Optimmune®). I find that the topical solution to be very effective, easier for clients to instill, and cheaper in long-term usage compared to the ointment preparation. If the STT is greater than 4 mm wetting per minute, there is a 80-85% chance for improvement with cyclosporine therapy. If the initial STT is less than 2 mm wetting per minute, there is a 60-65% improvement in tear production after starting CSA therapy. Topical antibiotics are prescribed to control and to prevent local ocular infections. Broad-spectrum antibiotics are recommended twice daily.
KCS is a controlled, often not curable syndrome. Therapy usually is for life! For cases refractory to topical and oral therapies, a parotid duct transposition can be considered. This surgery replaces the dry eye with salivary secretions. Although saliva does not have the exact composition as tears, saliva is a very good substitute in most cases of dry eyes. Complications of a parotid duct transposition include: the risk of anesthesia, salivary precipitates unto the eye, excessive facial wetting, and stenosis of the parotid duct.
The term pannus, or nowadays more appropriately named, chronic superficial keratitis (or CSK) literally denotes corneal pigmentation and vascularization. Pannus or CSK is a commonly diagnosed corneal disorder that we observe most frequently in the German Shepherd Dog. Other breeds affected with CSK include the Greyhound, Siberian Husky, Belgian Shepherd, Poodle, and Miniature Pincher.
The cause of CSK is unknown, but we consider it to be an immune-mediated disease whereby corneal antigens have been altered, and an autoimmune reaction is occurring. Ultraviolet radiation and elevation have additive effects in the severity of this disorder. Furthermore, young affected dogs seem to have a more aggressive and unforgiving corneal disease. The clinical signs seen with CSK are the classical pigmentation and vascularization, typically occurring at the lateral aspect of the cornea. With time, the lesion will progress to cover the entire cornea. An atypical form of CSK is seen where the third eyelid is solely affected, and we call this condition "atypical pannus" or "plasmoma." Both corneal and third eyelid diseases can occur at the same time. The diagnosis of CSK or pannus is straightforward. The typical corneal lesions affecting the lateral aspect of the cornea in a German Shepherd ( or other predisposed breed ) are evidence enough for the diagnosis of pannus. Cytology can be obtained from either a corneal or third eyelid scraping to yield lymphocytes or plasma cells. Diagnosis, however, is usually made on a clinical basis. Treatment for CSK is varied depending upon the extent of the lesions. Remember that a markedly pigmented cornea will be more difficult to treat than an earlier lesion of mild corneal pigmentation and vascularization. Also, young affected dogs are more resistant to therapy. Equally important to therapy is the education of your client that CSK is a life-long disease without cure! We are trying to control the disease, but a cure is never obtained. The mainstay of therapy is topical steroids. I prefer to use either topical dexamethasone or prednisolone acetate TID-QID. In addition to topical steroids, I frequently add topical cyclosporine therapy (2 % drops or Optimmune® ointment BID). Subconjunctival steroids can be administered for severe corneal lesions, but I prefer not to give subconjunctival injections unless all other avenues of therapy have been first exhausted. Once you give a subconjunctival injection, you are committed to one month of reposital corticosteroid therapy!!! Cryosurgery has been used by some, but I would not advocate its common practice for pannus. Superficial keratectomy can be performed to remove advanced corneal pigmentation, but one is limited to 2-3 keratectomies per eye, and topical corticosteroid therapy will have to be used soon after surgery to halt the next "wave" of advancing corneal pannus. Beta-irradiation with a Strontium 90 probe is an excellent choice for advanced pannus, but these probes are available at university settings. Pannus or chronic superficial keratitis is a common corneal disease that requires lifetime therapy. Control of ocular signs is the goal with cures not possible.
Corneal Dystrophy and Degeneration
The term Corneal Dystrophy is best used for a corneal opacity which is bilateral and symmetrical in presentation, has a familial basis, is not associated with inflammation, is not progressive (or minimally progressive), and is not associated with a systemic disorder. Corneal dystrophies typically involve the superficial epithelial or anterior stromal layer of the cornea, but there also exists a subcategory of dystrophies, which involve the corneal endothelium, causing bilateral, diffuse corneal edema. The superficial corneal dystrophies are commonly seen in the Siberian Husky, Bichon Frise, American Cocker Spaniel, Collie, German Shepherd, Shetland Sheepdog, and Cavalier King Charles Spaniel. The endothelial corneal dystrophies most commonly are observed in the Chihuahua, Boston Terrier, and the Dachshund. The superficial corneal lesions rarely need therapy, for the animals usually are not symptomatic. The endothelial dystrophies frequently result in diffuse corneal edema and the formation of bullae (bullous keratopathy). Topical hyperosmotic agents (such as 5% NaCl ointment) can be used with variable results. Thermal keratoplasties can be performed whereby the superficial aspect of the cornea is delicately cauterized with a special low-temperature ophthalmic cautery unit. Penetrating keratoplasty (or a corneal transplant) can be attempted in the very advanced cases of blinding corneal edema.
In contrast to corneal dystrophy, Corneal Degeneration occurs secondary to pathologic changes within the cornea. Lipid, cholesterol, calcium or a combination thereof are often deposited in the lesion. Corneal degenerations are unilateral or bilaterally asymmetrical, often associated with inflammation (vascularization and / or pigmentation), and may be associated with a systemic disorder (such as hypothyroidism, Cushing's disease or metabolic derangements of cholesterol or triglyceride metabolism). Therapy for corneal degeneration depends upon the extent of the lesion. Several therapies include the following: topical ophthalmic lubricants (to improve the tear film), cyclosporine (to improve the tear film and to provide immunomodulatory function), calcium binders such as EDTA (to bind to the calcific material), and topical antibiotics (to prevent against infection). Surgical options include a superficial keratectomy (to remove the degenerative material), conjunctival grafts (to provide support), excimer laser ablation of the lesions, corneal cyanoacrylate application, and donor corneal transplants.
Episcleritis Or Nodular Granulomatous Episcleritis
Episcleritis, or the inflammation of the tissue underlying the conjunctiva and overlying the sclera, can present to the clinician in several fashions. We can observe a focal elevation of the scleral-episcleral-conjunctival tissue especially near the limbus. This focal elevation can present as a tumor-like growth. Many times, we will call this a focal episcleritis or a nodular granulomatous episcleritis (NGE). In addition, we can see a diffuse infiltration of the episcleral tissue, emanating around the limbus in one or both eyes. Episcleritis often is a clinical diagnosis, but ultimately biopsy of the affected lesion is the definitive diagnosis. Histopathologic features of episcleritis are consistent with those of chronic granulomatous inflammation. Differential diagnosis for episcleritis and NGE-like lesions include: neoplasia, excessive granulation tissue, cysts, foreign body, focal infections, granulomas, and uveitis to name a few. Breeds predisposed to episcleritis include the Collie, Shetland Sheepdog, Cocker Spaniel, Rottweiler, and Labrador Retriever. Therapeutic options for episcleritis are multiple, and include: surgical debulking with adjunctive cryotherapy, beta-irradiation, intralesional corticosteroid injections, topical steroid therapy, topical cyclosporine solution, oral corticosteroid, azathioprine and the combination of tetracycline and niacinamide administration. For initial therapy, I like to obtain a biopsy of the affected lesion to confirm the diagnosis and then to perform cryotherapy of the surgical site. If the owners are reluctant to perform surgery or if the patient is a poor anesthetic candidate, topical or oral medications can be attempted. Frequently, I will give an intralesional injection of betamethasone or triamcinolone, as well as to administer topical corticosteroid drops (dexamethasone or prednisolone acetate). If the dog responds favorably to therapy, the treatment regime is tapered to daily or every other day frequency. If the animal does not respond to topical medications or if the patient is difficult to treat with topical solutions, then oral immunosuppressive therapy can be attempted. Oral prednisone can be prescribed, but I find that oral azathioprine (1-2.0mg/kg once daily for 3 days, then 0.75 to 1.0 mg/kg every 3 to 7 days) is an excellent therapeutic option in many cases of episcleritis. Toxic side effects with azathioprine include: vomiting, diarrhea, hepatotoxicosis, and myelosuppression. Recently, some ophthalmologists have reported success with oral administration of the combination of tetracycline and niacinamide for episcleritis in dogs. My experience with this combination of medications has been less than satisfactory. In addition, oral interferon (Roferon-A®, 80 IU/dog/day) has been found to be quite successful in cases of idiopathic ocular granulomatous diseases in collies (R.C. Riis, Abstract, Annual ACVO meeting, Montreal, 2000).
Corneal neoplasia is rare, and many times actually arise from the limbal region. Examples of corneal tumors include adenocarcinoma, papilloma, fibrosarcoma, hemangioma, hemangiosarcoma, limbal melanoma, and corneal lymphosarcoma. Prognosis will depend on tumor type, infiltration, and associated ocular abnormalities.
UNIQUE CORNEAL LESIONS OF THE CAT
Feline herpesvirus is caused by feline rhinotracheitis virus-1 (FHV-1). A wide spectrum of clinical syndromes may be observed in the feline herpes patient. Herpesvirus commonly causes keratitis, and may also contribute to the formation of conjunctivitis, as well. In fact, the scenario of keratitis in the face of an associated conjunctivitis is almost always due to feline herpesvirus. In kittens, FHV-1 is one of the agents responsible for the neonatal ophthalmia syndrome, whereby an infection is observed under the closed eyelids. Herpesvirus frequently causes corneal ulceration, which can present as punctate keratitis, dendritic ulcers (looks like a dendrite of an axon), geographic keratitis (large corneal infections and ulcers), and stromal keratitis (often due to an immune reaction to altered viral or corneal antigens). Diagnosis is based on clinical presentation (keratitis / conjunctivitis, symblepharon, eosinophilic conjunctivitis, etc), the presence of intranuclear inclusion bodies on cytology, pathognomic lesions such as dendritic ulcers, and laboratory testing which include immunofluorescence (IFA frequently results in false negative results) and polymerase chain reaction (PCR). At this time, PCR is considered the most sensitive test for FHV-1. However, available PCR testing has been less than satisfactory from available clinical laboratories. Therapy for FHV-1 include the use of topical antiviral agents such as trifluridine (Viroptic®), idoxuridine (obtained from a compounding pharmacy), and adenine arabinoside (Vira-A®) for a minimum of 4-6 times daily initially for the first week, oral L-lysine (250-500 mg orally BID mixed in the food), and other agents such as oral or topical interferon, acyclovir (50 mg every 12 hours for no more than 14 days), and famcyclovir (125 mg: ¼ tablet orally twice daily for 8 days). Treatment with topical antiviral medications and oral L-lysine can last for months at a tapered dose. The prognosis for FHV-1 infection is generally fair to good, but always warn owners of the necessary long-term therapy and potential for frequent recurrences. Several sequelae to FHV-1 infection in cats include corneal sequestrum formation, symblepharon (the adhesion of conjunctiva to conjunctiva or to the cornea), dry eye formation (KCS), and the presence of eosinophilic conjunctivitis or eosinophilic keratitis.
Corneal Sequestrum Formation
Corneal sequestrum formation is a unique condition to the feline eye (also has recently been described in the equine eye). Also known as corneal nigrum, corneal mummification, and corneal necrosis, sequestrum formation can result from any condition leading to chronic corneal irritation. Examples include feline herpesvirus infection, entropion, distichiasis, exposure keratitis, trauma, KCS, lagophthalmos, and genetic predisposition as seen in the Persian and Himalayan breed. There are two main thoughts for treatment of corneal sequestrum formation with those treating the eyes topically with ophthalmic preparations until the sequestrum sloughs off, and those who surgically remove the sequestrum with a keratectomy and corneal grafting techniques. Because I have observed several cats with corneal sequestra, which have perforated when allowed to slough off on their own, rather to surgically remove the lesion, I prefer to remove the sequestrum with a keratectomy and then to perform a corneoconjunctival transposition or conjunctival graft procedure.
Eosinophilic keratitis is another unique ocular syndrome to the cat (also seen in equine patients), which is readily diagnosed with a corneal scraping and cytology or a corneal biopsy (not necessary in most cases). The corneal cytology demonstrates an infiltration of eosinophils, mast cells or a combination of the two cell types. Single to multiple progressive lesions are observed to originate from the limbus (often at the lateral aspect of the eye, but can be seen as a medial lesion, as well). Treatment for eosinophilic keratitis includes topical and systemic anti-inflammatory agents. Topical dexamethasone or prednisolone are effective to control the lesion, as well as oral megestrol acetate (Ovaban®). The author tends not to use the above medications for concern to recrudesce a latent herpesvirus infection or for the secondary side effects seen with megestrol acetate. I prefer to use topical cyclosporine (1.5% to 2%) solution two to three times daily as initial therapy. Control, not cure, of the lesion is the ultimate goal.
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