Cornea Notes PDF

Cornea Learning Objectives 1) Be able to list the 4 layers of the cornea and describe the function of each layer and consequences of dysfunction. 2) Be able to describe the healing response of the cornea to epithelial and stromal ulcerative defects. 3) Be able to list the causes of corneal edema, va...

Cornea Learning Objectives 1) Be able to list the 4 layers of the cornea and describe the function of each layer and consequences of dysfunction. 2) Be able to describe the healing response of the cornea to epithelial and stromal ulcerative defects. 3) Be able to list the causes of corneal edema, vascularization, pigmentation. 4) Be able to list the common causes of corneal ulceration. 5) Be able to list the critical goals in the treatment of animals with corneal ulcers. 6) Given a clinical scenario involving a corneal ulcer, be able to outline an appropriate management approach, including appropriate diagnostics and medical/surgical therapies. 7) Be able to describe the common clinical features of and appropriate treatment for canine spontaneous chronic corneal epithelial defect (SCCED) 8) Be able to recognize corneal abscess and list appropriate treatment options for the condition. 9) Be able to recognize chronic superficial keratitis (German Shepherd pannus) and describe appropriate management of the condition. 10) Be able to recognize equine immune-mediated keratitis and describe appropriate treatment. 11) Be able to recognize lipid keratopathy and list etiologies for the condition. 12) Be able to recognize corneal endothelial dystrophy/degeneration and list potential complications of and treatment options for the condition. 13) Be able to recognize equine/feline eosinophilic keratoconjunctivitis and list appropriate treatment options for the condition. 14) Be able to recognize feline corneal sequestrum and list appropriate treatment options for the condition. I. Anatomy and Physiology The cornea is the clear anterior portion of the fibrous tunic of the eye and continuous with the sclera at the limbus (corneoscleral junction). Histologically, the cornea is composed of an outer non-keratinized squamous epithelium, a collagenous stroma, an inner acellular membrane (Descemet’s membrane, which is the basement membrane of the corneal endothelium), and a single layer of flattened cells, the corneal endothelium at the inner aspect. The stroma comprises 90% of the corneal thickness. Normally, the cornea is optically clear. This is largely due to the absence of blood vessels, the non-keratinized nature of the epithelium, regular lamellar arrangement of stromal collagen, small diameter of collagen fibrils. The cornea is maintained in a state of relative dehydration through an active pump mechanism in the corneal endothelium, which pumps fluid from the cornea into the anterior chamber. An intact corneal surface epithelium also provides a barrier to fluid from the tear film entering the corneal stroma. The pre-corneal tear film lubricates and nourishes the corneal surface and maintains an optically uniform corneal surface. The anterior cornea is richly innervated with non-myelinated sensory nerve fibers and is therefore extremely sensitive to touch, trauma, etc. II. Function The cornea functions as a protective barrier and is the major refractive structure of the eye, focusing light onto the retina. Maintenance of clarity is therefore of central importance to the cornea’s role in vision. Many corneal diseases and/or responses to disease result in a decrease in the clarity of the cornea, with a corresponding negative effect on vision. 1 III. Corneal Healing and Pathologic Responses To deduce etiologies of corneal pathology and how medical and/or surgical interventions will affect the cornea, it is important to understand the normal healing response of the cornea and the typical responses of the cornea to insults. Defects in the corneal epithelium (i.e. corneal ulcers) heal by the adjacent epithelium sliding over the area and then undergoing mitosis to eliminate the defect. This begins very quickly (within an hour or so of injury). Because the epithelium (being hydrophobic) normally prevents fluid (tear film) from entering the cornea, defects in the epithelium result in focal corneal edema. Once the epithelial defect heals, the corneal endothelium will pump out this excess fluid, thereby restoring corneal clarity. Corneal stromal defects are also covered by sliding and mitosis of adjacent epithelium. In addition, fibroblasts (arising from stromal cells called keratocytes) begin to proliferate and lay down new collagen. However, this newly formed collagen is irregularly arranged, which is the reason corneal scars are visibly apparent, even though they are composed of the same material as normal cornea. Corneal edema results in decreased transparency (i.e. cloudiness) because the accumulated fluid distorts the organized lamellar arrangement of the stromal collagen fibrils. Edema may result from one of two general conditions: epithelial defects (which allow fluid from the tear film to leak into cornea) or corneal endothelial dysfunction (due to decreased pump function). In the absence of a corneal epithelial defect (i.e. ulcer), corneal edema is usually caused by some form of endothelial dysfunction. The corneal endothelium does not have the capacity to regenerate in the adult animal. Therefore, extensive loss or degeneration of corneal endothelium results in permanent corneal edema. Corneal vascularization may occur in response to corneal, scleral, or intraocular disease. Blood vessels grow in from the limbus towards the site of the corneal defect. Although a growth rate of 1mm/day is commonly quoted, the rate of vascular ingress in individual cases is extremely variable and impacted by many things, including disease and treatment factors. Blood vessels in response to surface corneal disease (e.g. ulceration, KCS) are typically superficial and undergo substantial branching, whereas blood vessels associated with intraocular disease are generally deeper in the cornea, appear much straighter and enter the cornea circumferentially. Corneal pigmentation occurs in response to chronic corneal inflammation or irritation. The source of the inflammation may be repeated corneal ulceration, chronic abrasion (e.g. trichiasis or entropion), KCS (dry eye), chronic corneal exposure due to an inability to blink, among others. Melanocytes enter the cornea from the limbus, often in association with corneal neovascularization. Of companion animal species, corneal pigmentation is most commonly see in dogs, particularly in brachycephalic breeds, IV. Disorders of the Cornea Congenital Disorders Microcornea and megalocornea are congenitally small and large corneas, respectively. They are both rare conditions and generally associated with multiple ocular anomalies. Dermoid is the most common congenital corneal abnormality and is a corneal mass of ectodermal and mesodermal origins. It often arises at the lateral limbal conjunctiva and extends onto the cornea, typically appearing as a haired mass. It has gross and histopathologic characteristics of normal skin with associated adnexal structures (hair, etc). Complete surgical excision is curative. 2 Persistent pupillary membranes (PPMs; discussed/defined in the Uvea notes) arise from the iris and may be attached to the endothelial surface of the cornea, causing focal/multifocal opacities. Treatment is impractical and unnecessary. Ulcerative Keratitis Corneal ulceration is a full-thickness loss of corneal epithelium, which exposes underlying stroma. In contrast, corneal erosion is a partial-thickness loss of epithelium. Corneal ulcers are one of the most common ophthalmic problems for which animals are presented to veterinarians. They are characterized by acute onset ocular pain and blepharospasm, localized corneal edema, conjunctival hyperemia, and epiphora. Purulent ocular discharge may be present if secondary microbial infection occurs. Corneal ulcers are extremely painful. Because of the anatomic distribution of corneal sensory nerve fibers, superficial ulcers are often more painful than deep stromal ulcers or descemetoceles (a condition where corneal ulceration has extended to Descemet’s membrane). Corneal ulcers are often traumatic in origin and the source of injury may be exogenous (e.g. foreign body, stick, cat claw) or endogenous (e.g. trichiasis, ectopic cilia, distichia, entropion). Other common causes of ulcers include KCS, exposure keratitis, herpesvirus infection, chemical contact, etc. Upon initial clinical presentation, a search for an underlying cause should always be performed. The intact corneal epithelium is a formidable barrier to microbial (bacterial or fungal) invasion. However, loss of the epithelium allows secondary infection by such organisms, where they often play a role in progression of the ulcer. In dogs (and cats), secondary corneal infections are generally bacterial in nature; mycotic corneal infection does occur, but is much less common in small animal species than it is in horses. Most of the time, when infected ulcers are discussed, it is in reference to a secondary infection of the ulcer. However, there are a few infectious agents that can cause corneal ulcers in host species, including feline herpesvirus-1, canine herpesvirus, equine herpesvirus-2, Moraxella bovis (infectious bovine keratoconjunctivitis) and Chlamydophila pecorum (in sheep/goats). Characterization of ulcers is important to determining appropriate management strategies, as well as to appropriately document ulcer healing or progression. Corneal ulcers may be classified as superficial, stromal (mid- or deep stromal), or descemetoceles. In the latter condition, only Descemet’s membrane and endothelium remain intact and the eye is very fragile/susceptible to rupture. Another important clinical classification is a condition referred to as a melting ulcer. This is a severe condition in which proteolytic degradation of corneal stromal collagen occurs, resulting in rapid destruction of the cornea. The enzymes responsible for this condition may be elicited by bacterial agents (esp. Pseudomonas spp.) or from neutrophils recruited to the area due to the presence of ulceration and/or infection. The classic appearance of a melting ulcer is a very soft surface where the affected tissue may actually appear to be sagging/melting. Management: Diagnostics Fluorescein stain – hydrophilic stain, so does not stain intact corneal epithelium but will bind to exposed corneal stroma and stain it bright green. Fluorescein staining is therefore useful in diagnosing the presence of ulceration and demarcating it’s borders during monitoring of progression/resolution; a cobalt blue light source increases the sensitivity of this test by causing the stain to fluoresce. Descemet’s membrane does not stain with fluorescein. Search for etiology/underlying cause – this should include assessment of aqueous tear production by Schirmer tear test (esp in dogs), confirming ability to blink, close visual inspection for trichiasis, ectopic cilia, entropion, retained foreign body, etc. Corneal cytology - may be useful in determining presence of infection by detecting bacteria or fungal elements in sample; Gram staining may help direct antibiotic choice. 3 Culture/Sensitivity - should be performed if infection is suspected based upon the presence of purulent ocular discharge, especially if ulceration is deep or melting. Should also perform if ulcers are progressive despite antibiotic treatment. Therapeutics Topical antibiotics - should be applied in all cases of ulceration; frequency depends on severity of ulcer and, more specifically, presence of infection. Application should be TID in uncomplicated superficial ulceration; presence of infection dictates more frequent use (up to hourly in severe, established infections!). Use broad-spectrum antibiotics or base choice on culture/sensitivity results. Topical antibiotics must be continued until the corneal epithelial defect is closed, as determined by negative fluorescein stain retention. NOTE: systemic antibiotics have little to no role in the management of corneal ulcers. Topical atropine sulfate - diminishes ciliary body spasm, which improves patient comfort. SIDBID use is sufficient in most cases. Contraindicated in cases with concurrent glaucoma. Atropine may decrease tear production, thereby complicating ulcer healing, so use judiciously. Protease inhibitors - indicated in rapidly progressive or melting ulcers. These agents may slow corneal stromal degradation from bacterial and endogenous proteases. Several agents are reportedly beneficial in this regard, but topical acetylcysteine and autogenous serum are the most commonly utilized in veterinary practice. Oral tetracyclines (e.g. tetracycline, doxycycline, minocycline) are also beneficial, as tetracyclines are potent protease inhibitors and accumulate in the corneal stroma following systemic administration. Conjunctival flap surgery - indicated for deep stromal ulceration (>50% corneal depth), melting ulcers, and descemetoceles. Flaps provide a direct vascular supply to assist in healing (through antimicrobial and antiproteolytic activity). They also provide mechanical strength, fibroblasts, and epithelial cells. NOTE: 3rd eyelid flaps are contraindicated in most cases of corneal ulceration, especially when infection is present. Although simple to perform, they are not a simple substitute for a conjunctival flap, as they provide none of the same benefits. Uncomplicated, superficial corneal ulcers generally heal very rapidly (within a few days), whereas more complicated ulcers, or those with secondary infection take a more protracted course, requiring several days to weeks in some instances. Topical corticosteroids are CONTRAINDICATED in cases of corneal ulceration! Use of an Elizabethan collar should be considered in cases where self-trauma is occurring. This is particularly important in cases of deep ulceration or descemetoceles, where corneal rupture may result from the patient rubbing the eye. Spontaneous Chronic Corneal Epithelial Defect (SCCED) (aka Boxer ulcer, Indolent ulcer) This is a specific ulcerative condition of the cornea in which the lesion remains superficial, but heals very slowly (if at all). Synonyms for this condition include Boxer ulcer, recurrent erosion syndrome, indolent ulcer, and refractory ulcer syndrome, among others. They occur in many breeds, but seem especially common in the Boxer. Most often, this condition occurs in middleaged to older individuals. There is a defect in the superficial corneal stroma that prevents normal attachment of the corneal epithelium to the stroma. These ulcers are often characterized by being superficial with a rim of loose corneal epithelium around the ulcer’s edge. Signs of ocular pain are quite variable, as is corneal vascularization which may be absent or robust. There are several recommended treatments for this condition. The initial step of treatment is debridement of all non-adherent epithelium from the cornea with a dry cotton-tipped applicator under topical anesthetic. Sometimes the ulcer initially appears to be just a few millimeters in 4 diameter, but extends to involve most of the cornea following debridement. Most commonly, debridement is followed by a keratotomy (although several other procedures are also effective). Striate keratotomy - utilizing a 25 to 27 gauge needle, the affected cornea is lightly scored in a grid pattern with striations placed approximately 0.5-1 mm apart, starting and ending in normal epithelium. Burr keratotomy – a specialized corneal diamond burr is utilized to abrade the corneal surface in the affected area. NOT ALL NON-HEALING ULCERS ARE SCCED! Do not perform these procedures unless you have ruled out other causes of non-healing and are confident in your diagnosis!! Apply broad spectrum topical antibiotics TID until healed. Usually takes 7-10 days to heal following surgery. Adjunctive medications to manage discomfort are also warranted (e.g. systemic NSAIDs). Feline Herpesvirus Keratitis Corneal manifestations of FHV-1 include dendritic ulcers, geographic ulcers, and stromal keratitis. Dendritic ulceration is considered pathognomonic for FHV-1. These small, branching corneal defects often do not extend to the stroma and are therefore more easily detected with rose Bengal stain than fluorescein stain. Geographic ulcers are large, irregular ulcerations, which are probably caused by coalescing dendritic ulcers. Stromal keratitis is characterized by severe corneal edema, deep vascularization, and cellular infiltration of the cornea. Concurrent corneal ulceration may be present, but the corneal edema generally exceeds the degree expected from the ulcer (i.e. usually see small ulcers, but diffuse corneal edema). Topical antibiotics should be employed if ulceration is present. Topical antivirals appear to help speed recovery in some cases, but this is unpredictable. To have a reasonable chance for effectiveness, some topical antivirals must be applied very frequently (at least 6 times daily). The exception is topical cidofovir (must be compounded), which can be used BID. Oral famcyclovir has demonstrated efficacy as an antiviral drug in FHV cases. Canine Herpesvirus Keratitis While canine herpesvirus-1 infection is ubiquitous, ocular manifestations are uncommon to rare. May present as an ulcerative (commonly dendritic) or non-ulcerative keratoconjunctivitis. Most dogs that manifest clinical ocular disease are immunocompromised, usually due to immunosuppressive therapy. The condition is self-limiting, but routine treatment of superficial ulcers, as necessary, is indicated. Topical antivirals may also be helpful in reducing duration of disease. Infectious Bovine Keratoconjunctivitis Infectious bovine keratoconjunctivitis (IBK) is the most common and economically important ocular disease of cattle. The responsible infectious agent is Moraxella bovis, although numerous co-infections may impact severity of disease outbreaks. M. bovis is highly contagious, via direct contact and transmission by mechanical vectors (most notably the face fly). Bacterial virulence factors (pili and cytotoxin), host factors (age, breed, immunity, stress, nutrition, etc) and environmental factors (UV radiation; dry, dusty environments) all play into disease outbreaks. Initial clinical signs include blepharospasm, epiphora and photophobia. Conjunctivitis and central corneal ulceration occur early in disease and ulceration may progress to corneal rupture. Efficacy of vaccines is quite variable and preventative measures to control other risk factors (flies, dust, etc) are critical to prevention and control. Many antibiotics and routes of administration have demonstrated good efficacy against M. bovis. Systemically administered long acting oxytetracycline and tulathromycin are labeled for use in the U.S. Subconjunctival antibiotic administration (esp Penicillin G) and topical administration of antibiotics are very effective, but herd size limits the practicality of these treatment approaches. 5 Corneal Foreign Body Foreign bodies may become embedded in the corneal epithelium or may penetrate deep into the stroma. In some cases, sharp materials may perforate the cornea. As would be expected, corneal foreign bodies are associated with significant discomfort. Removal of superficial foreign bodies is easily achieved under topical anesthesia by flushing (most effectively achieved utilizing a small bore catheter to create a fluid jet), utilizing a cotton-tipped applicator, jewelers’ forceps, or a hypodermic needle to tease the material out of the cornea. Be aware that it may be difficult to determine how deeply embedded the object may be and one may suddenly be faced with a perforated globe following removal of deeply penetrating foreign bodies. Unless one is comfortable with the surgical management required in such an event, specialist referral should be considered when deep or full-thickness corneal penetration is suspected. Corneal Laceration/Perforation Superficial corneal lacerations may be managed as an ulcer, whereas deep lacerations (>50% corneal thickness) should be sutured primarily. Corneal perforation may occur due to a number of causes, including rupture of a deep ulcer, sharp trauma (e.g. cat scratch injury), or blunt trauma. Rupture of the cornea is often associated with prolapse of a portion of the iris, which may seal the defect. Depending on the cause of rupture, hyphema, lens perforation, and retinal detachment may also be present. Corneal perforation is a surgical condition. However, appropriate medical measures should be taken until the surgical repair can be performed. Emergency management: Topical antibiotics - broad spectrum bactericidal topical antibiotics (q4-6 hours) should be applied in all cases. Solutions are preferred over ointments in cases of an open globe. Topical atropine sulfate - utilize BID-TID; again solution is preferred over ointment. Systemic antibiotics - broad spectrum systemic antibiotics should be instituted due to potential for intraocular infection. An E-collar should be applied to prevent worsening of condition through self-trauma. Prognosis: The prognosis for vision in cases of corneal rupture varies widely, but is generally fair to good. The prognosis is worsened by the following: - rupture due to blunt trauma (often indicated by a rupture at or extending beyond limbus) - cases with associated severe hyphema - cases with associated lens rupture (lens usually must be removed to prevent phacoclastic uveitis) - cases with obvious intraocular infection - chronic rupture Non-ulcerative Corneal Disease Corneal Abscess A corneal abscess is a stromal accumulation of inflammatory cells, appearing as an off-white to yellow opacity within the cornea. Significant discomfort is usually evident. Corneal edema and vascularization are usually present, as is reflex uveitis. Compared to corneal ulcers, this condition is uncommon, but is seen more commonly in large animals (esp horses) than small animals. The cause of corneal abscess is often unknown, but may be associated with subepithelial infection (bacterial or fungal) or it may be sterile, associated with an entrapped foreign body. Treatment involves the use of a topical antibiotic capable of penetrating intact corneal epithelium (e.g. topical fluoroquinolones). The condition will usually resolve when vascularization infiltrates the affected region of cornea. A more rapid and definitive method of treatment involves 6 keratectomy to surgically remove the abscessed tissue in conjunction with a conjunctival flap or other surgical procedure to assist in corneal healing. Pigmentary keratitis Pigmentary keratitis is a descriptive term, not a specific diagnosis. The condition is most common in the dog and some breeds, particularly the Pug, are more commonly and severely affected than others. Corneal pigmentation generally occurs secondary to chronic irritation and, as such, vascularization is also often present. Common underlying causes include KCS, nasal fold trichiasis, entropion, distichiasis, exposure keratitis (especially in brachycephalic breeds), and recurrent corneal ulceration. It may also accompany conditions such as chronic superficial keratitis (pannus). Pigmentation may progress to cause vision deficits or blindness. Treatment is aimed at addressing the underlying cause. Although the pigment can be surgically removed by keratectomy, it usually recurs. Topical cyclosporine or tacrolimus may reduce pigmentation in some cases. Chronic superficial keratitis (CSK) Commonly referred to as pannus or German Shepherd pannus because of the fact that this condition most often affects German Shepherds and their crosses. Other overrepresented breeds include the Greyhound, Borzoi, Border Collie, English Springer Spaniel, Dachshund, and Australian Cattle dogs. Clinical signs include superficial vascularization and pigmentation of the cornea, usually starting at the temporal (lateral) cornea and progressing centrally. The lesions are often slightly raised and may eventually cover the entire cornea. There are often faint white corneal infiltrates (corneal lipid) at the leading edge of the advancing corneal lesions. The condition is non-ulcerative and is non-painful. Third eyelid thickening and depigmentation (plasmoma) may occur concurrently. Chronic superficial keratitis is thought to be an immune-mediated condition. Manifestations are more severe at high altitude, due to increased UV exposure. Generally speaking, the younger the individual is at age of onset, the more severe and poorly-responsive to treatment is the condition. As with most immune-mediated condtions, CSK cannot be cured. Control is possible, but lifelong treatment is required to maintain remission. Treatment typically involves topical antiinflammatory/immune-suppressive medications (corticosteroids and/or cyclosporine or tacrolimus). The frequency of use depends on severity and responsiveness. I typically use both classes of medications initially BID-TID and then taper corticosteroids off, keeping the patient only on cyclosporine for long-term use (if sufficient to control signs). In many patients, the disease can be controlled with once daily or every other day medication, although flare-ups may occur requiring intensifying the treatment. Very severe cases may require subconjunctival corticosteroid injection, keratectomy and cryotherapy, or local radiation treatment (i.e. Strontium 90). Other forms of immune-mediated keratitis in the dog are occasionally encountered, but are not as well characterized as CSK. Similarities include non-painful corneal vascularization without apparent cause and responsiveness to similar treatments as CSK. Equine Immune-Mediated Keratitis (IMMK) Equine IMMK is a minimally to non-painful condition that may be unilateral or bilateral. There are 4 typically recognized classifications, based upon clinical appearance and region of cornea involved. These include epithelial, superficial stromal, mid-stromal and endothelial. Corneal vascularization and stromal cellular infiltrate are common with the stromal forms of the disease and uncommon in the epithelial and endothelial forms. The epithelial and stromal forms of the condition are variably responsive to topical corticosteroids, topical cyclosporine or tacrolimus. Subconjunctival cyclosporine implants are also effective at controlling disease. The endothelial form of equine IMMK causes diffuse corneal edema and is refractory to treatment. 7 ICH Keratouveitis (“Blue Eye”) Occasionally, vaccination for infectious canine hepatitis (canine adenovirus) will induce a syndrome of uveitis and endotheliitis, as the result of a type III (antigen-antibody immune complex) reaction against the virus. Signs initially occur 10-14 days following vaccination, and include severe corneal edema, endothelial precipitates, and anterior uveitis, which sometimes progresses to glaucoma. Interestingly, the condition is often unilateral. This condition was much more common with CAV-1 vaccines than the CAV-2 vaccines that are currently used. Lipid Keratopathy Lipid deposition in the cornea may occur either: - as an inherited condition (corneal lipid dystrophy) - in association with a systemic lipid metabolism disturbance (corneal lipid degeneration) - in association with previous or ongoing corneal disease (corneal lipid degeneration) Corneal lipid appears as a crystalline, refractile (sparkly) or white amorphous accumulation. It is usually quite superficial but may affect all layers of the cornea. Lipid dystrophy (inherited) tends to be bilaterally symmetrical and self-limiting; generally does not interfere with vision. Corneal lipid accumulation as a result of systemic disease (e.g. hypothyroidism, fasting hyperlipidemia) is also usually bilaterally symmetrical. When associated with other corneal disease (e.g. previous corneal ulceration, pannus, NGE), it may or may not be bilateral. When lipid accumulation is associated with systemic lipid metabolism disorders or corneal disease, it is more appropriately referred to as lipid degeneration. Because these conditions are usually not sight threatening treatment is typically not recommended, though keratectomy may be curative. Dietary fat restriction may help in select cases. Note: Chronic topical corticosteroids may cause or exacerbate lipid keratopathy. Corneal Mineralization Occurs in the dog, horse and more rarely in other spp. Usually seen in older patients as a degenerative condition, but may also be caused by systemic calcium/phosphorous imbalance and chronic uveitis (especially in equine recurrent uveitis cases). The mineralization is often diffuse and affects all layers of the cornea, though it is most dense superficially. Superficial keratectomy may be helpful in select cases. Topical EDTA is often recommended due to its ability to chelate calcium, but this treatment generally does not result in substantial resolution. EDTA may be more effective when applied topically as an intensive treatment in conjunction with surgical removal of epithelium. Endothelial Dystrophy/Degeneration This is a condition characterized by spontaneous and premature degeneration of corneal endothelial cells resulting in severe bilateral corneal edema. Predominantly a canine condition. This condition is non-painful. Diffuse corneal edema in the presence of ocular discomfort should prompt considerations of other conditions that cause diffuse edema (e.g. anterior uveitis, glaucoma). This condition is seen almost exclusively in dogs. Predisposed breeds include the Boston Terrier, Chihuahua, Dachshund, and Basset Hound, though others may also be affected. The condition typically affects middle-aged to older individuals. The edema usually starts at the temporal aspect of the cornea and progresses across the cornea, to result in complete corneal edema and associated loss of vision. Chronic severe edema results in the formation of corneal epithelial bullae, which may rupture, resulting in recurrent corneal ulceration. Medical treatment includes topical antibiotics when ulcerations occur. Topical hyperosmotic solutions/ointments may help draw some fluid from the cornea, but visible clearing of the cornea is rare with this treatment. Although visibly apparent clearing usually does not occur, topical hyperosmotics (e.g. 5% NaCl ointment) may pull enough fluid from the cornea to decrease the formation/rupture of epithelial bullae. 8 Surgical treatments, including placement of a very thin conjunctival flap over the affected region of cornea and thermal keratoplasty (fine point cautery to coagulate affected corneal stroma) may be appropriate in some cases. Thermal keratoplasty is indicated primarily when recurrent or nonhealing corneal ulceration is problematic. Eosinophilic keratitis/keratoconjunctivitis This condition is seen in cats and horses and is characterized by variably sized raised, proliferative lesions/plaques on the corneal surface. EK is a painful condition, corneal vascularization is typically present and small white multifocal nodules may be scattered over the corneoconjunctival surfaces. Concurrent corneal ulcers may be present. The condition may be uni- or bilateral. Some studies have suggested an association between FHV-1 and EK in cats. Diagnosis is made by corneoconjunctival cytology, which reveal numerous eosinophils and mast cells, as well as lymphocytes and plasma cells. Topical corticosteroids are often effective treatment (TID initially and then tapered to lowest effective dosing), although relapses are common when medication is discontinued. Topical cyclosporine is also efficacious in some cases. Topical megesterol acetate has also been shown to be an effective treatment and is without known side effects, although it must be compounded. Oral megesterol acetate (Ovaban) is very effective at controlling this condition in cats, but potential systemic side effects should render this a treatment of last resort. In the horse, corneal ulcers are commonly associated with EK and are very slow to heal. Surgical excision of the ulcerated lesions is often necessary to achieve healing. Systemic corticosteroids and antihistamines may be helpful in some equine cases. Corneal Sequestrum This condition affects cats only and is characterized by a tan to black plaque in the central or paracentral cornea. Vascularization generally accompanies the lesion. Affected cats are usually very painful. Persians and Himalayans seems predisposed to this condition, but any breed may be affected. The pathogenesis is unclear, but non-healing corneal ulcers almost always precede the development of corneal sequestrum. Suspected etiopathogenic factors include qualitative tear film abnormalities and FHV-1 infection (in nonbrachycephalic breeds). Removal by keratectomy is curative in most cases, but recurrence is possible. Placement of a conjunctival graft following keratectomy may lessen recurrence rates. Several other surgical treatments are utilized, including partial or full-thickness corneal transplantation and corneoconjunctival transposition. When conservatively managed (i.e. doing nothing), some affected animals will eventually slough the sequestrum. This may take several weeks/months and should only be recommended if the patient is non-painful. Non-Neoplastic Corneal or corneoscleral Masses Several similar inflammatory conditions affect both the sclera and adjacent cornea, termed episcerokeratitis. These include ocular nodular fasciitis (ONF), nodular granulomatous episclerokeratitis (NGE), and fibrous histiocytoma. They are more fully described in the notes on scleral disease and conjunctival disease. Corneal epithelial inclusion cysts are uncommon but caused by dysregulated growth of epithelial cells underneath the normal epithelium or within corneal stroma. Traumatic deposition of epithelial cells into deeper tissues, where they grow unchecked, is the presumed pathogenesis. They are non-painful. If large, they can be surgically excised, which is curative. Corneal Neoplasia Neoplasia arising from the cornea itself is extremely rare. Squamous cell carcinoma (SCC) of the cornea most commonly affects the horse, typically arising as a corneoconjunctival lesion at the 9 limbus. In dogs, SCC has been reported to arise from corneas affected with chronic keratitis, particularly secondary to chronic KCS (dry eye). Corneal hemangioma/hemangiosarcoma is uncommonly reported; most common in the dog. Rarely, lymphosarcoma can manifest in the cornea of dogs and cats. Scleral or limbal neoplasms may affect the adjacent cornea by infiltration. This is especially common with limbal melanoma in dogs and cats. In both species, this is typically a benign neoplasm. 10