How to Diagnose the Cloudy Eye

Home , Corneal opacity, Equine Recurrent Uveitis, Keratitis, Synechia (eye)

Caroline Monk, DVM*; Nicole Scherrer, DVM; and Mary L. Utter, DVM, Diplomate ACVO

Authors’ addresses: University of Florida, College of Veterinary Medicine, 2015 SW 16th Ave., Gainesville, FL 32608 (Monk); University of Pennsylvania, New Bolton Center, 382 West Street Road, Kennett Square, PA 19348 (Scherrer, Utter); e-mail: monkc@uﬂ.edu. *Corresponding and present- ing author. © 2013 AAEP.

1. Introduction ● Stromal abscess ● Diagnosing the cloudy equine eye is often met with Calcific band keratopathy ● trepidation in the field setting because of the variety Eosinophilic keratitis ● Nonulcerative keratouveitis of differentials for this condition, many of which ● are clinically difficult to distinguish. Most equine Onchocerciasis ● Squamous cell carcinoma veterinarians feel comfortable with diagnosis and ● Subepithelial keratomycosis treatment of uncomplicated corneal ulceration be- ● Immune-mediated keratitis cause of its high prevalence in equine practice. ● Equine recurrent uveitis However, the cloudy eye with intact epithelium is a ● Glaucoma less common complaint and can prove to be a diag- nostic challenge. Furthermore, accurate diagnosis 2. Materials and Methods is vital. Treatment for one condition is often con- For the initial ophthalmic examination, the same traindicated for another, particularly with regard to basic tools are needed as for any ophthalmic ambu- the use of corticosteroids. The importance of accu- latory procedure. rate diagnosis and treatment is accentuated by the ● fact that maintenance of a clear visual axis is often Fluorescein stain ● Mepivicaine or lidocaine for local nerve blocks a necessity for the career of the equine patient. ● ␣ Equine eyes have the propensity to degenerate rap- Chemical restraint: 2-agonist sedation (xy- lazine, detomidine) idly, leaving very little room for error. The objec- ● Focal light source with cobalt-blue filter tive of this report is to present a stepwise approach ● Dimly lit area to diagnosis of the cloudy equine eye. Correct diagnosis will allow accurate treatment. Step 1: Is the Eye Painful? The disease processes that will be discussed in- Examination should start with a patient who has clude the following: not yet been sedated and whose eyelids have not

NOTES

AAEP PROCEEDINGS ր Vol. 59 ր 2013 181 HOW-TO SESSION: OPHTHALMOLOGY

Fig. 1. Determining the degree of ocular pain.

been blocked, to allow accurate assessment of ocular pain. Hallmark clinical signs of ocular pain include epiphora and blepharospasm. Determining the degree of ocular pain is important for formulation of differential diagnoses of corneal opacity (Fig. 1). Fig. 2. Corneal edema. After gross assessment for pain through a visual examination, the function of cranial nerves II, III, V, and VII is assessed by the menace response, dazzle reflex, pupillary light reflexes (direct and indirect), ● Edema: hazy gray-blue, can be focal or dif- and palpebral reflex. Pupil size, shape, and symme- fuse (Fig. 2) try between right and left pupils should be evalu- ● Vessels: originate from the limbus ated. Miosis, mydriasis, and anisocoria may occur ● Perfused or ghost coincident with corneal disease, the most common ● Depth indicates location of inciting lesion examples being when the corneal opacity is associ- ● Superficial–branching ated with anterior uveitis, synechia, or glaucoma. ● Deep–hedge ● Fibrosis: gray, may note associated ghost Step 2: Is There an Ulcer? vessels After assessment of vision and reflexes, the horse ● Inflammatory cell infiltrate: yellow to green can be sedated and perineural anesthesia can be discoloration performed if needed. If corneal culture is war- ● Lipid or mineral infiltrate: shiny white, crys- ranted, that should occur before instilling any topi- talline (cholesterol or calcium) cal solutions into the eye. The eye must be stained with fluorescein, even if it does not appear that a It is vital to be able to recognize these processes corneal ulcer is present. The only way to determine when examining an eye with corneal disease. fluorescein stain uptake accurately is with use of a cobalt-blue filter light. Use of a focal light source is Step 4: Making the Diagnosis key to careful examination of corneal opacities. A systematic approach should be used every time, so (1) Diseases Generally Characterized by a that no area is missed, even if the lesion is immedi- Nonpainful Eye ately apparent. Start at the limbus and examine If initial assessment shows the patient to have nor- circumferentially, moving axially toward a more mal ocular comfort, the differential diagnosis list is central part of the cornea as you proceed. Often significantly shortened. Any disease that has a dimming the focal light source and taking breaks component uveitis is excluded from this category, will improve the tractability of the patient. Be sure because the condition is typically painful (Fig. 3). to examine both eyes. (a) Immune-mediated keratitis (IMK) should be considered as a differential for a nonpainful eye with Step 3: What Color Is the Opacity? corneal vascularization.1 In IMK, vascularization The cornea readily displays pathologies as the result depth generally corresponds to the depth of the le- of its biologically clear appearance. Furthermore, sion. There are often striking corneal changes it has a limited number of characteristic reactions while the eye is quiet and comfortable (Fig. 4). to disease. The ability to visually recognize these The specific pathogenesis of this disease is not reactions allows for accurate differentiation of kera- known, and the clinical presentation can be highly topathies. The following is a list of the equine cor- variable. The unifying characteristics of the dis- nea reaction to disease accompanied by its clinical ease are the ocular comfort of the patient and the appearance: lesion response to immunosuppressive therapy.

182 2013 ր Vol. 59 ր AAEP PROCEEDINGS HOW-TO SESSION: OPHTHALMOLOGY

Fig. 3. Differentials for the non-painful, cloudy eye.

Ruling out an infectious cause through culture or opacities that resolve with anti-fungal therapy. Cul- empirical antimicrobial therapy is important when ture results of these lesions are variable. There- making this diagnosis because the cornerstone of fore, it is important to rule out an infectious disease therapy for IMK is immunosuppression with such as this, for example, with initial treatment of corticosteroids. empirical antimicrobial therapy before treating for (b) Similar in appearance to IMK but of in- immune-mediated disease. 2 fectious origin is subepithelial keratomycosis. (c) Another differential for a nonpainful corneal Horses with this disease only exhibit mild to no opacity is the most common tumor of the equine blepharospasm. Hallmark corneal changes are cornea—corneal squamous cell carcinoma.3 This multifocal punctate to geographic cellular infiltrate can originate from the cornea, conjunctiva, or limbus. Although lesions commonly appear nodular and elevated, some may appear simply as stromal infiltrate (Fig. 5). Notably, all of the forms should cause little to no discomfort. When squamous cell carcinoma is high on the differential diagnosis list, biopsy is needed for diagnosis. This may be in the form of keratectomy under general anesthesia if the lesion is smooth and cannot be grasped for easy removal. (d) End-stage glaucoma can manifest as a comfortable, cloudy eye. The corneal opacity in this case is usually edema.4 This corneal change is often accompanied by other gross changes such as buphthalmos and striae, and the eye is usually blind. (e) Despite its chronicity, fibrosis may be newly noted by a client or seen on initial examination such Fig. 4. IMK of manifests with striking corneal changes. as during a pre-purchase exam. Corneal scars vary

AAEP PROCEEDINGS ր Vol. 59 ր 2013 183 HOW-TO SESSION: OPHTHALMOLOGY characteristic of these diseases. This infiltrate may be located in any area of the cornea and at any depth. Nonspecific signs of ocular pain and severe inflammation are concurrent. The gold standard for diagnosis and differentiation of both diseases is histopathology; however, this requires general anesthesia. Therefore, often the diagnosis may be made by response to therapy because the intact epithelium usually prevents adequate cytology and culture. (c) A differential for the cloudy, painful eye with diffuse or focal corneal edema is uveitis. Anterior uveitis alone without primary corneal disease may manifest as the result of equine recurrent uveitis8 or ocular trauma. In these cases, the predominant Fig. 5. Some neoplastic lesions appear as stromal infiltrate. corneal change is diffuse corneal edema. Extensive neovascularization or cellular infiltrate should not be present. Clinical signs of note are miosis, often severe, and circumlimbal vascularization. Careful significantly in size and density. The deeper the inspection of the quality, opacity, and coloration of injury, the denser the scar; they should appear the cornea should allow for differentiation. white, consolidated, and smooth, with no ocular dis- (d) Early glaucoma is another differential for comfort (see Fig. 6). painful, diffuse corneal edema, especially that which (2) Diseases Generally Characterized by a Painful does not respond to anti-inflammatory medication. Eye In the early, acute stage, the eye may be painful. Measurement of intraocular pressure is the gold If the eye is painful, a wide variety of conditions are standard for diagnosis of this disease and will be possible (Fig. 7). discussed later. However, a sign to differentiate (a) Both eosinophilic keratitis and calcific band this edema from that of uveitis without the ability to keratopathy appear as raised corneal lesions. measure pressure is through pupil size. A uveitic However, they can be differentiated on the basis of pupil is most often miotic, whereas an early glau- cytology and location. Eosinophilic keratitis is coma pupil without synechia should be at least characterized by numerous eosinophils on cytology 5 slightly mydriatic. Often, vertical corneal edema and is typically limbal (Fig. 8). Conversely, cal- with linear band opacities is noted. cific band keratopathy should be both negative for (e) Finally, onchocerciasis may also appear as a eosinophils and infectious causes and is typically painful opacity usually located limbally with ac- distributed in the interpalpebral fissure. companying signs of corneal inflammation (edema, (b) For a smooth, intact epithelium, differentiat- vascularization). The most common concurrent ing between a focal lesion and segmental disease can clinical sign, conjunctivitis, distinguishes it from sometimes be difficult. Anterior uveitis is often other corneal infiltrates.9 Definitive diagnosis is secondary to discrete opacities created by nonulcer- made through a conjunctival snip biopsy. ative keratouveitis (NUKU)6 and stromal abscessa- 7 tion (Fig. 9). Severe, diffuse corneal edema may Step 5: Further Diagnostics mask the whitish to yellow cellular infiltrate that is Once the initial examination has been performed, further diagnostics are often warranted for definitive diagnosis. (a) Applanation or rebound tonometry. This is needed to accurately diagnose glaucoma and uveitis by providing an objective measurement of intraocular pressure. Tonometry facilitates early diagnosis of glaucoma, which is often subtle. Comparison between globes within a horse as well as comparison of published reference ranges is helpful. This diag- nostic is vital to monitoring response to treatment for glaucoma. (b) Culture and cytology. Culture and cytology are a frustrating aspect to nonulcerative corneal disease. Because of the intact epithelium, a diag- nostic sample is difficult to obtain. Cytology is a Fig. 6. Scars should appear white, consolidated, and smooth, requirement for diagnosis of certain conditions with no ocular discomfort. (eosinophilic keratitis). It also can guide therapeu-

184 2013 ր Vol. 59 ր AAEP PROCEEDINGS HOW-TO SESSION: OPHTHALMOLOGY

Fig. 7. If the eye is painful, a wide variety of conditions are possible.

tic choices even if definitive diagnosis cannot be fore analysis. If scraping of the lesion for cytology obtained. Therefore, an attempt at culture and cy- has created ulceration caused by poorly adherent tology can be made with the knowledge that an epithelium, a second culture should be obtained of inconclusive sample or sterile culture is not defini- the exposed stroma. tive. Culture can be obtained with the use of a (c) Biopsy. Biopsy of corneal tissue should only sterile cotton-tipped applicator culturette on the cor- be performed with extreme caution. Rupture of the neal surface. After this, cytology can be obtained globe as the result of structural instability is more after the application of topical anesthetic agent (pro- common in equids than other veterinary species. paricaine, tetracaine) with the use of the blunt end Globe rupture is a surgical emergency, and eyes can of a sterile scalpel blade. Gently scrape the mar- only be saved if prompt surgical intervention is per- gins of the opacity, and smooth the sample onto formed. A proliferative, nonpainful lesion is the glass slides. The slides should then be stained be- best candidate for corneal field biopsy. (d) Referral for keratectomy. This procedure requires heavy sedation or general anesthesia. It is indicated both for diagnosis of a deep stromal opacity through histopathology but also is a treatment to remove neoplastic or infected corneal tissue. The importance of an accurate diagnosis is high- lighted by the decision to treat the eye with topical corticosteroids. Corticosteroids have been shown to decrease vascularization and limit potentially blinding anterior uveitis.10 Conversely, they also inhibit epithelial regeneration and can predispose the ocular surface to infectious colonization.11–13 It is veterinary dogma never to use a topical steroid when a corneal ulceration is present. However, other contraindications also exist. An infection may still be present because of the difficulty to obtain a positive culture through the intact epithelium. Furthermore, horse eyes appear to be more susceptible to the adverse effects of topical corticosteroids and infectious colonization. If a culture Fig. 8. Eosinophilic keratitis is characterized by numerous eo- cannot be obtained and diagnosis is open, initially, sinophils on cytology and is typically limbal. presumptive treatment with topical antimicrobials

AAEP PROCEEDINGS ր Vol. 59 ր 2013 185 HOW-TO SESSION: OPHTHALMOLOGY would be examined through the use of slit-lamp biomicroscopy. This allows for a more precise assessment of depth and composition by means of microscopic inspection. However, the cost and learning curve associated with these devices typically precludes their use for the general practitioner. Instead, the general practitioner is often put in a position of doing an in-depth corneal examination with limited tools and must therefore be careful not to miss any subtle clinical signs. Referral should always be offered, especially in cases in which the diagnosis is not straightforward or the eye fails to respond to therapy. References 1. Giler B, Michau T, Salmon J. Immune-mediated keratitis in horses: 19 cases (1998–2004). Vet Ophthalmol 2005;8: 233–239. 2. Brooks D, Plummer C, Mangan B, et al. Equine subepithelial keratomycosis. Vet Ophthalmol 2013 Mar;16(2):93–96. Fig. 9. Severe inflammation and pain accompany stromal 3. Dugan S, Curtis C, Roberts S, et al. Epidemiologic study of abscessation. ocular/adenexal squamous cell carcinoma in horses. JAm Vet Med Assoc 1991;198:251–256. 4. Wilcock B, Brooks D, Latimer C. Glaucoma in horses. Vet Pathol 1991;28:74–78. is indicated. If the eye fails to respond, corticoste- 5. Yamagata M, Wilkie D, Gilger B. Eosinophilic kerato- roids then may be justified with caution. Finally, conjunctivitis in a horse. J Am Vet Med Assoc 1994;205: frequent reassessments are vital because eyes are 1308–1311. highly dynamic, and clients may not perceive subtle 6. Brooks D, Millichamp N, Peterson M, et al. Nonulcerative keratouveitis in five horses. J Am Vet Med Assoc 1990;196: changes in disease processes. 1985–1991. 7. Hendrix D, Brooks D, Smith P, et al. Corneal stromal ab- 3. Results scesses in the horse: a review of 24 cases. Equine Vet J When a systematic and consistent approach is used 1995;27:440–447. 8. Schwink KL. Equine uveitis. Vet Clin North Am Equine to examine and diagnose ocular lesions, you are less Pract 1992;8:557–574. likely to miss subtle clinical signs and prescribe 9. Schmidt G, Krehbiel J, Coley S, et al. Equine ocular on- inappropriate therapy. Once the correct diagnosis chocerciasis: histopathologic study. Am J Vet Res 1982;42: is made, searching for current therapies is simpli- 1371–1375. fied. Inappropriate use of corticosteroids can be di- 10. Nien C, Flynn K, Chang M, et al. Reducing peak corneal haze after photorefractive keratectomy in rabbits: pred- sastrous in the equine eye, and therefore careful nisolone acetate 1.00% versus cyclosporine A 0.05%. J Cat- examination and thought should be given before aract Refract Surg 2011;27:937–944. their administration. 11. Barton M. Equine keratomycosis. Compendium. 1992; 14:936–950. 12. Bourcier T, Borderie V, Forgez P, et al. In vitro effects of 4. Discussion dexamethasone on human corneal keratocytes. Invest Oph- Characterizing a lesion on the basis of the hallmark thalmol Vis Sci 1999;40:1061–1070. 13. Hendrix D, Ward D, Barnhill M. Effects of anti-inflamma- corneal changes as well as the use of a stepwise, tory drugs and preservatives on morphologic characteristics logical approach allows for the more accurate diag- and migration of canine corneal epithelial cells in tissue nosis of corneal disease. Ideally, all corneal lesions culture. Vet Ophthalmol 2002;5:127–135.

186 2013 ր Vol. 59 ր AAEP PROCEEDINGS