Corneal disease (Proceedings)

This article will discuss common corneal conditions and recommended management for dogs and cats.

Indolent ulcers are a very common condition seen in dogs. There are multiple names for the condition, including "Boxer Ulcer", SCCED, Refractory ulcer, and recurrent epithelial erosion. This condition is seen almost exclusively in middle aged to older dogs (> 6 years old). They often occur spontaneously with no known trauma. The apparent discomfort level can be greatly variable, from intense blepharospasm to minimal signs of pain. Typical clinical signs include mild corneal cloudiness +/- corneal vascularization. Fluorescein stain will reveal a superficial ulcer with characteristic non adherent epithelial cells adjacent to the ulcer. The vascular response can be aggressive or non-existent.

Histopathology of affected corneas reveals a loss of normal basement membrane and the presence of a characteristic acellular hyalinized zone on the superficial stroma. The basement membrane in non-affected areas of the same cornea is normal, suggesting that this is not a basement membrane dystrophy as was previously thought. The acellular hyalinized zone likely interferes with the formation of normal adhesion complexes between the epithelial basal cells and the superficial stroma.

Various medications have been used to help encourage healing of these ulcers. Topical antibiotics are the mainstay of treatment, but are often overused. Indolent ulcers are rarely infected, thus antibiotic therapy is prophylactic. Topical antibiotics with minimal toxic effect on growing epithelial cells are used at a frequency of once to twice daily until healing has occurred. Tobramycin is a common choice. Serum is an effective treatment for stromal, melting ulcers, but does not seem to have significant benefit for indolent ulcers. EDTA, PSGAGs, chondroitin sulfate, cyanoacrylate (tissue glue), Substance P, IGF, and MMP inhibitors have all been used with varying success, often in combination with other procedures.

Surgical procedures are generally recommended for the treatment of indolent ulcers. Simple manual debridement is the most common procedure performed. Either a sterile cotton swab or a blade can be used, but I feel a blade is more effective. The epithelium should be debrided until it no longer is easily removed. This procedure can be repeated multiple times until healing occurs or done prior to more aggressive techniques. Linear Grid Keratotomy and Multifocal Superficial Punctate Keratotomy are both variations of a procedure known as anterior stromal micropuncture. These are effective at facilitating healing and are very low risk procedures. There are multiple theories as to why these procedures work. The disruption of the acellular hyalinized zone may allow healing epithelial cells a gap for adhesion complex formation. It has also been suggested that they increase the production of various cytokines and growth factors which improve the healing response. These procedures leave minimal corneal scarring when performed correctly and can be performed without general anesthesia. Laser keratoplasty and thermokeratoplasty involve the creation of multiple anterior stromal "burns" for the purpose of disrupting the acellular zone on the ulcer surface, much like the LGK. I reserve these for corneas with significant corneal edema or for ulcers not responsive to multiple micropuncture attempts. Superficial keratectomy involves the surgical excision of the anterior stroma in the affected area. This is a very effective technique at healing the ulcer, however it is more expensive and technically difficult than the previous techniques. I have never had to resort to this surgery to heal an indolent ulcer.

Stromal ulcers include any corneal defect that, through the process of proteolysis, has eroded through the stroma. These are considerably more serious in terms of the health of the eye and have the potential to result in loss of the eye if not treated appropriately. Proteolytic enzymes from both bacterial toxins as well as bystander effect from WBCs and fibroblasts are responsible for the progression. Aggressive treatment is necessary.

Deep ulcers should be evaluated based on size, depth, location, corneal consistency, and the location of corneal vascularization. Surgery is an option for any ulcer greater than 50% depth, but non-surgical mehods can be effective for many deep ulcers if the conditions are right. Work-up of stromal ulcers should include a culture and sensitivity as well as corneal cytology to help determine the causative agent. Bacteria agents are the most common offenders (esp. P. aeruginosa and B-hemolytic Streptococcus), but fungal keratitis has been reported in dogs and cats. Antibacterial therapy is ideally tailored to the culture and sensitivity results, but this is not always practical. A gram stain can be performed to give immediate direction as to the type of antibiotic that should be used. For most deep ulcers, especially ones with a malacic appearance, the antibiotic should be given frequently initially (q 2-4 hours) to saturate the cornea. After several days, I reduce the frequency to QID until the ulcer is sufficiently healed.

A mydriatic, such as atropine, is often used, especially in cases of very deep ulcers where perforation is a very real concern. This helps prevent iris entrapment in the corneal wound should perforation occur and can improve the patient's comfort. BID dosing for several days is usually sufficient.

Antiprotease therapy has recently been determined to be a very important part of therapy. These medications are useful in stopping the collagenolysis and preventing further progression of the ulcer. These are particularly useful for malacic ulcers. Various products have been tested, and most found to be quite effective at limiting enzyme activity. Serum is among the most common agent used for this purpose because it is readily available, cheap, and effective. It is important that the serum be kept sterile and should be refrigerated at all times. Any serum remaining after one week should be discarded and a fresh sample drawn if necessary. EDTA, N-acetyl-cysteine, and Doxycycline are also commonly used and reportedly effective antiprotease medications. All topical treatments should be given every 1-2 hours initially and then reduced to 3-4 times daily.

Pain control is an important component to treatment. Topical medications include atropine and compounded morphine. Oral medications such as Tramadol or NSAIDs are also effective. For severe stromal ulcers that have incited a secondary uveitis, systemic NSAIDs may be the best choice to reduce the intraocular inflammation while improving comfort.

Elizabethan collars are important to prevent self-trauma from exacerbating the ulcer. Hot compresses are also helpful several times a day to improve blood flow to the area, but I don't recommend them for descemetoceles or extremely deep ulcers that could rupture if excessive pressure is accidently placed on the eye. Exercise should be restricted and frequent rechecks are recommended until the ulcer is sufficiently healed.

Surgery is recommended for most stromal ulcers, especially if they are greater than 75% depth, rapidly progressive, or malacic. The purpose of surgery is to provide increased corneal protection, improve the structural integrity, and improve the blood supply to the affected area. Several options exist. A temporary tarsorrhaphy or third eyelid flap is performed to reduce exposure of the cornea and provided limited protection while the healing process occurs naturally. While quick and inexpensive, these procedures do not offer a huge advantage over simple medical management as they still rely on the animal's innate healing ability. However, I have seen nice results with these procedures, especially in relatively exophthalmic breeds and young cats. Conjunctival grafts are probably the most common type of surgery performed for deep ulcers. The conjunctival pedicle graft is the most common form, but other variations exist. Conjunctival grafts are very effective at healing deep and infected corneal defects. They bring immediate tectonic support and vascular supply to the area. It is not a technically difficult surgery, although the best results are obtained with magnification and ophthalmic suture (8-0 or 9-0). The primary disadvantage is the potential for a large and vision impairing corneal scar. This is the procedure of choice for peripheral or malacic ulcers, especially when vision is already compromised due to other conditions (cataracts). When possible, I feel a corneoconjunctival transposition is a preferable technique. This procedure involves creating a partial thickness corneal flap extending from the ulcer to the limbus. This flap, along with the connected conjunctiva, is advanced into the ulcer to bring tectonic support. The primary benefit of this surgery is that clear cornea is advanced into the ulcer, resulting in decreased scarring of the central cornea and a better visual outcome. Additionally, the transposed cornea is thicker and provides more support than a thin sheet of conjunctiva. The main disadvantages are that a blood supply is not immediately brought to the ulcer, there is permanent adhesion of conjunctiva and a noticeable limbus line peripherally, and it is technically more difficult. Other grafting materials that have been used successfully include porcine intestinal submucosa, amniotic membrane, A-cell, and frozen corneal grafts.

Corneal perforations are a special subset of deep stromal ulcers. They may be due to acute trauma, as with a cat claw, or due to a progressive stromal ulcer. When a perforation occurs, the immediate release of fibrin and inflammatory cells into the anterior chamber will result in a fragile seal of the wound, but often not before significant changes have occurred. If iris becomes entrapped in the perforation, surgery to patch the cornea is more difficult and the long term prognosis is not as good, with increased risks of glaucoma and uveitis. If the lens capsule is damaged at the time of the injury, immediate phacoemulsification is typically recommended to prevent a phacoclastic uveitis. General treatment for perforations is as for stromal ulcers with a much greater emphasis placed on surgical techniques.

Autoimmune disease of the cornea presents in several different and distinct syndromes. The most common is Pannus (Chronic Superficial Keratitis or CSK). German Shepherds are by far the most common breed to be affected with this condition. Grayhounds also commonly develop this condition, but with a less consistent pattern of clinical signs. Typical pannus is characterized by a thickened, hyperemic third eyelid with loss of the pigmented leading edge, ventrolateral scleral pigmentation, and corneal vascularization with or without pigment. Untreated, this condition will progress to complete corneal pigmentation and visual impairment. Fortunately, pannus is typically responsive to chronic therapy with topical corticosteroids or immunomodulating medications such as cyclosporine or tacrolimus.

Superficial punctuate keratitis is another manifestation of autoimmune disease in the cornea. Dachshunds are the primary breed known to develop this condition, but I have seen it several times in Shetland Sheepdogs as well. Affected dogs typically present with multiple white punctuate opacities scattered throughout the cornea. There is no discernable pattern and the cornea may or may not be ulcerated over the opacities. Pain, as evidenced by lacrimation and blepharospasm, is also variable. This is one of several exceptions to the general rule stating topical corticosteroids should not be used on an ulcerated cornea. Treatment is with topical corticosteroids, cysclsporine, or tacrolimus.

Eosinophilic keratitis is a condition essentially unique to cats (and rarely horses). It presents as progressive corneal vascularization +/- superficial ulceration. Most cats show no signs of discomfort. The distinguishing feature is the multiple white plaques that form on the corneal surface over the vascularized cornea. A corneal scraping and cytology will typically reveal multiple inflammatory cells, often including eosinophils and plasma cells. This condition often presents to the ophthalmologist as a "nonhealing corneal ulcer" that has been unresponsive to multiple topical antibiotics. Treatment for eosinophilic keratitis involves topical corticosteroids on a long term, tapering schedule. Advanced cases may benefit from the use of oral prednisone or megestrol acetate (Ovaban) in addition to the topical medication, but I rarely find this necessary. Lifelong therapy may be required. Due to the possible link to feline herpes virus, oral L-Lysine is often initiated along with the topical medications.

Corneal endothelial disease is divided into cases of hereditary dystrophy vs. acquired degeneration. The primary clinical sign is corneal edema due to insufficient number of functional endothelial cells to adequately remove fluid from the corneal stroma. Endothelial dystrophy is typically seen in Boston Terriers, Chihuahuas, and long haired Dachshunds. It presents as progressive corneal edema that starts in the lateral cornea and is not associated with any other abnormality. The dog is comfortable and normally visual, even in cases of diffuse edema. It is often referred for possible glaucoma, but the normal tonometry values, normal PLR, and lack of ocular inflammation rule out glaucoma. Endothelial degeneration/decompensation is acquired after some intraocular insult, such as uveitis, anterior lens luxation, or intraocular surgery. Localized or diffuse edema is seen. While this condition is not associated with any discomfort by itself, these corneas are more prone to corneal ulceration through the formation of corneal bullae. These "blisters" on the cornea can rupture leading to recurrent superficial or stromal ulcers. While there is not treatment to reverse the edema since endothelial cells are poorly regenerative in dogs and cats, topical 5% sodium chloride may help to decrease bullae formation and reduce the incidence of corneal ulcers. For severe cases, a laser keratoplasty or thermokeratoplasty can be performed which is effective in preventing further ulcers by creating a layer of anterior stromal fibrosis.

Another condition that is unique to cats (and again rarely horses) is a corneal sequestrum. This presents as a discolored area of the cornea, usually centrally. It can be anywhere from a light tan to black in color and may be subepithelial or ulcerated. They typically cause no discomfort if the epithelium is intact over the plaque. If the plaque protrudes beyond the epithelium, blepharospasm is often present. Corneal vascularization is also variable. The exact nature of these plaques remains unknown, but they do arise as a consequence of chronic corneal irritation, such as chronic herpes viral keratitis, entropion, and recurrent ulcers. Recent studies have shown that the pigment in these sequestra is melanin. Persian, Himalayan, and Colorpoint breeds are predisposed to developing sequestra. Several management options exist. Medical management involves close monitoring for the plaque to slough off the front of the cornea naturally. This most often occurs in cases where there is aggressive corneal vascularization that forms a corneal vascular bed beneath the sequestrum. Intermittent corneal debridement with a blade may help speed the process. The alternative is a surgical keratectomy. I prefer this method of management as it allows the sequestrum to be removed under controlled, surgical conditions and for the placement of a tectonic graft if the keratectomy is sufficiently deep. Treatment for feline herpes virus is also recommended due to several studies that have documented an increased incidence of the viruses in corneas with sequestra.