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How to Diagnose the Cloudy 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: [email protected]. *Corresponding and present-ing author. © 2013 AAEP.

1. Introduction

Diagnosing the cloudy equine eye is often met withtrepidation in the field setting because of the varietyof differentials for this condition, many of whichare clinically difficult to distinguish. Most equineveterinarians feel comfortable with diagnosis andtreatment of uncomplicated corneal ulceration be-cause of its high prevalence in equine practice.However, the cloudy eye with intact epithelium is aless common complaint and can prove to be a diag-nostic challenge. Furthermore, accurate diagnosisis vital. Treatment for one condition is often con-traindicated for another, particularly with regard tothe use of corticosteroids. The importance of accu-rate diagnosis and treatment is accentuated by thefact that maintenance of a clear visual axis is oftena necessity for the career of the equine patient.Equine eyes have the propensity to degenerate rap-idly, leaving very little room for error. The objec-tive of this report is to present a stepwise approachto diagnosis of the cloudy equine eye. Correct diag-nosis will allow accurate treatment.

The disease processes that will be discussed in-clude the following:

● Stromal abscess● Calcific band keratopathy● Eosinophilic keratitis● Nonulcerative keratouveitis● Onchocerciasis● Squamous cell carcinoma● Subepithelial keratomycosis● Immune-mediated keratitis● Equine recurrent uveitis● Glaucoma

2. Materials and Methods

For the initial ophthalmic examination, the samebasic tools are needed as for any ophthalmic ambu-latory procedure.

● Fluorescein stain● Mepivicaine or lidocaine for local nerve blocks● Chemical restraint: �2-agonist sedation (xy-

lazine, detomidine)● Focal light source with cobalt-blue filter● Dimly lit area

Step 1: Is the Eye Painful?Examination should start with a patient who hasnot yet been sedated and whose eyelids have not

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HOW-TO SESSION: OPHTHALMOLOGY

NOTES

been blocked, to allow accurate assessment of ocularpain. Hallmark clinical signs of ocular pain includeepiphora and blepharospasm. Determining the de-gree of ocular pain is important for formulation ofdifferential diagnoses of corneal opacity (Fig. 1).After gross assessment for pain through a visualexamination, the function of cranial nerves II, III, V,and VII is assessed by the menace response, dazzlereflex, pupillary light reflexes (direct and indirect),and palpebral reflex. Pupil size, shape, and symme-try between right and left pupils should be evalu-ated. Miosis, mydriasis, and anisocoria may occurcoincident with corneal disease, the most commonexamples being when the corneal opacity is associ-ated with anterior uveitis, synechia, or glaucoma.

Step 2: Is There an Ulcer?After assessment of vision and reflexes, the horsecan be sedated and perineural anesthesia can beperformed if needed. If corneal culture is war-ranted, that should occur before instilling any topi-cal solutions into the eye. The eye must be stainedwith fluorescein, even if it does not appear that acorneal ulcer is present. The only way to determinefluorescein stain uptake accurately is with use of acobalt-blue filter light. Use of a focal light source iskey to careful examination of corneal opacities.A systematic approach should be used every time, sothat no area is missed, even if the lesion is immedi-ately apparent. Start at the limbus and examinecircumferentially, moving axially toward a morecentral part of the cornea as you proceed. Oftendimming the focal light source and taking breakswill improve the tractability of the patient. Be sureto examine both eyes.

Step 3: What Color Is the Opacity?The cornea readily displays pathologies as the resultof its biologically clear appearance. Furthermore,it has a limited number of characteristic reactionsto disease. The ability to visually recognize thesereactions allows for accurate differentiation of kera-topathies. The following is a list of the equine cor-nea reaction to disease accompanied by its clinicalappearance:

● Edema: hazy gray-blue, can be focal or dif-fuse (Fig. 2)

● Vessels: originate from the limbus● Perfused or ghost● Depth indicates location of inciting lesion● Superficial–branching● Deep–hedge● Fibrosis: gray, may note associated ghost

vessels● Inflammatory cell infiltrate: yellow to green

discoloration● Lipid or mineral infiltrate: shiny white, crys-

talline (cholesterol or calcium)

It is vital to be able to recognize these processeswhen examining an eye with corneal disease.

Step 4: Making the Diagnosis

(1) Diseases Generally Characterized by aNonpainful EyeIf initial assessment shows the patient to have nor-mal ocular comfort, the differential diagnosis list issignificantly shortened. Any disease that has acomponent uveitis is excluded from this category,because the condition is typically painful (Fig. 3).

(a) Immune-mediated keratitis (IMK) should beconsidered as a differential for a nonpainful eye withcorneal vascularization.1 In IMK, vascularizationdepth generally corresponds to the depth of the le-sion. There are often striking corneal changeswhile the eye is quiet and comfortable (Fig. 4).The specific pathogenesis of this disease is notknown, and the clinical presentation can be highlyvariable. The unifying characteristics of the dis-ease are the ocular comfort of the patient and thelesion response to immunosuppressive therapy.

Fig. 1. Determining the degree of ocular pain.

Fig. 2. Corneal edema.

182 2013 � Vol. 59 � AAEP PROCEEDINGS


Ruling out an infectious cause through culture orempirical antimicrobial therapy is important whenmaking this diagnosis because the cornerstone oftherapy for IMK is immunosuppression withcorticosteroids.

(b) Similar in appearance to IMK but of in-fectious origin is subepithelial keratomycosis.2

Horses with this disease only exhibit mild to noblepharospasm. Hallmark corneal changes aremultifocal punctate to geographic cellular infiltrate

opacities that resolve with anti-fungal therapy. Cul-ture results of these lesions are variable. There-fore, it is important to rule out an infectious diseasesuch as this, for example, with initial treatment ofempirical antimicrobial therapy before treating forimmune-mediated disease.

(c) Another differential for a nonpainful cornealopacity is the most common tumor of the equinecornea—corneal squamous cell carcinoma.3 Thiscan originate from the cornea, conjunctiva, or lim-bus. Although lesions commonly appear nodularand elevated, some may appear simply as stromalinfiltrate (Fig. 5). Notably, all of the forms shouldcause little to no discomfort. When squamous cellcarcinoma is high on the differential diagnosis list,biopsy is needed for diagnosis. This may be in theform of keratectomy under general anesthesia if thelesion is smooth and cannot be grasped for easyremoval.

(d) End-stage glaucoma can manifest as a com-fortable, cloudy eye. The corneal opacity in thiscase is usually edema.4 This corneal change is of-ten accompanied by other gross changes such asbuphthalmos and striae, and the eye is usuallyblind.

(e) Despite its chronicity, fibrosis may be newlynoted by a client or seen on initial examination suchas during a pre-purchase exam. Corneal scars vary

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

Fig. 4. IMK of manifests with striking corneal changes.



significantly in size and density. The deeper theinjury, the denser the scar; they should appearwhite, consolidated, and smooth, with no ocular dis-comfort (see Fig. 6).

(2) Diseases Generally Characterized by a PainfulEyeIf the eye is painful, a wide variety of conditions arepossible (Fig. 7).

(a) Both eosinophilic keratitis and calcific bandkeratopathy appear as raised corneal lesions.However, they can be differentiated on the basis ofcytology and location. Eosinophilic keratitis ischaracterized by numerous eosinophils on cytologyand is typically limbal5 (Fig. 8). Conversely, cal-cific band keratopathy should be both negative foreosinophils and infectious causes and is typicallydistributed in the interpalpebral fissure.

(b) For a smooth, intact epithelium, differentiat-ing between a focal lesion and segmental disease cansometimes be difficult. Anterior uveitis is oftensecondary to discrete opacities created by nonulcer-ative keratouveitis (NUKU)6 and stromal abscessa-tion (Fig. 9).7 Severe, diffuse corneal edema maymask the whitish to yellow cellular infiltrate that is

characteristic of these diseases. This infiltrate maybe located in any area of the cornea and at anydepth. Nonspecific signs of ocular pain and severeinflammation are concurrent. The gold standardfor diagnosis and differentiation of both diseasesis histopathology; however, this requires general an-esthesia. Therefore, often the diagnosis may bemade by response to therapy because the intact ep-ithelium usually prevents adequate cytology andculture.

(c) A differential for the cloudy, painful eye withdiffuse or focal corneal edema is uveitis. Anterioruveitis alone without primary corneal disease maymanifest as the result of equine recurrent uveitis8 orocular trauma. In these cases, the predominantcorneal change is diffuse corneal edema. Extensiveneovascularization or cellular infiltrate should notbe present. Clinical signs of note are miosis, oftensevere, and circumlimbal vascularization. Carefulinspection of the quality, opacity, and coloration ofthe cornea should allow for differentiation.

(d) Early glaucoma is another differential forpainful, diffuse corneal edema, especially that whichdoes not respond to anti-inflammatory medication.In the early, acute stage, the eye may be painful.Measurement of intraocular pressure is the goldstandard for diagnosis of this disease and will bediscussed later. However, a sign to differentiatethis edema from that of uveitis without the ability tomeasure pressure is through pupil size. A uveiticpupil is most often miotic, whereas an early glau-coma pupil without synechia should be at leastslightly mydriatic. Often, vertical corneal edemawith linear band opacities is noted.

(e) Finally, onchocerciasis may also appear as apainful opacity usually located limbally with ac-companying signs of corneal inflammation (edema,vascularization). The most common concurrentclinical sign, conjunctivitis, distinguishes it fromother corneal infiltrates.9 Definitive diagnosis ismade through a conjunctival snip biopsy.

Step 5: Further Diagnostics

Once the initial examination has been performed,further diagnostics are often warranted for defini-tive diagnosis.

(a) Applanation or rebound tonometry. This isneeded to accurately diagnose glaucoma and uveitisby providing an objective measurement of intraocu-lar pressure. Tonometry facilitates early diagnosisof glaucoma, which is often subtle. Comparison be-tween globes within a horse as well as comparison ofpublished reference ranges is helpful. This diag-nostic is vital to monitoring response to treatmentfor glaucoma.

(b) Culture and cytology. Culture and cytologyare a frustrating aspect to nonulcerative cornealdisease. Because of the intact epithelium, a diag-nostic sample is difficult to obtain. Cytology is arequirement for diagnosis of certain conditions(eosinophilic keratitis). It also can guide therapeu-

Fig. 5. Some neoplastic lesions appear as stromal infiltrate.

Fig. 6. Scars should appear white, consolidated, and smooth,with no ocular discomfort.



tic choices even if definitive diagnosis cannot beobtained. Therefore, an attempt at culture and cy-tology can be made with the knowledge that aninconclusive sample or sterile culture is not defini-tive. Culture can be obtained with the use of asterile cotton-tipped applicator culturette on the cor-neal surface. After this, cytology can be obtainedafter the application of topical anesthetic agent (pro-paricaine, tetracaine) with the use of the blunt endof a sterile scalpel blade. Gently scrape the mar-gins of the opacity, and smooth the sample ontoglass slides. The slides should then be stained be-

fore analysis. If scraping of the lesion for cytologyhas created ulceration caused by poorly adherentepithelium, a second culture should be obtained ofthe exposed stroma.

(c) Biopsy. Biopsy of corneal tissue should onlybe performed with extreme caution. Rupture of theglobe as the result of structural instability is morecommon in equids than other veterinary species.Globe rupture is a surgical emergency, and eyes canonly be saved if prompt surgical intervention is per-formed. A proliferative, nonpainful lesion is thebest candidate for corneal field biopsy.

(d) Referral for keratectomy. This procedurerequires heavy sedation or general anesthesia.It is indicated both for diagnosis of a deep stromalopacity through histopathology but also is a treat-ment to remove neoplastic or infected corneal tissue.

The importance of an accurate diagnosis is high-lighted by the decision to treat the eye with topicalcorticosteroids. Corticosteroids have been shownto decrease vascularization and limit potentiallyblinding anterior uveitis.10 Conversely, they alsoinhibit epithelial regeneration and can predisposethe ocular surface to infectious colonization.11–13

It is veterinary dogma never to use a topical steroidwhen a corneal ulceration is present. However,other contraindications also exist. An infectionmay still be present because of the difficulty to ob-tain a positive culture through the intact epithe-lium. Furthermore, horse eyes appear to be moresusceptible to the adverse effects of topical cortico-steroids and infectious colonization. If a culturecannot be obtained and diagnosis is open, initially,presumptive treatment with topical antimicrobials

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

Fig. 8. Eosinophilic keratitis is characterized by numerous eo-sinophils on cytology and is typically limbal.



is indicated. If the eye fails to respond, corticoste-roids then may be justified with caution. Finally,frequent reassessments are vital because eyes arehighly dynamic, and clients may not perceive subtlechanges in disease processes.

3. Results

When a systematic and consistent approach is usedto examine and diagnose ocular lesions, you are lesslikely to miss subtle clinical signs and prescribeinappropriate therapy. Once the correct diagnosisis made, searching for current therapies is simpli-fied. Inappropriate use of corticosteroids can be di-sastrous in the equine eye, and therefore carefulexamination and thought should be given beforetheir administration.

4. Discussion

Characterizing a lesion on the basis of the hallmarkcorneal changes as well as the use of a stepwise,logical approach allows for the more accurate diag-nosis of corneal disease. Ideally, all corneal lesions

would be examined through the use of slit-lampbiomicroscopy. This allows for a more precise as-sessment of depth and composition by means ofmicroscopic inspection. However, the cost andlearning curve associated with these devices typi-cally precludes their use for the general practitioner.Instead, the general practitioner is often put in aposition of doing an in-depth corneal examinationwith limited tools and must therefore be careful notto miss any subtle clinical signs. Referral shouldalways be offered, especially in cases in which thediagnosis is not straightforward or the eye fails torespond to therapy.

References1. 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 subepithe-lial keratomycosis. Vet Ophthalmol 2013 Mar;16(2):93–96.

3. Dugan S, Curtis C, Roberts S, et al. Epidemiologic study ofocular/adenexal squamous cell carcinoma in horses. J AmVet Med Assoc 1991;198:251–256.

4. Wilcock B, Brooks D, Latimer C. Glaucoma in horses.Vet Pathol 1991;28:74–78.

5. Yamagata M, Wilkie D, Gilger B. Eosinophilic kerato-conjunctivitis in a horse. J Am Vet Med Assoc 1994;205:1308–1311.

6. Brooks D, Millichamp N, Peterson M, et al. Nonulcerativekeratouveitis in five horses. J Am Vet Med Assoc 1990;196:1985–1991.

7. Hendrix D, Brooks D, Smith P, et al. Corneal stromal ab-scesses in the horse: a review of 24 cases. Equine Vet J1995;27:440–447.

8. Schwink KL. Equine uveitis. Vet Clin North Am EquinePract 1992;8:557–574.

9. Schmidt G, Krehbiel J, Coley S, et al. Equine ocular on-chocerciasis: histopathologic study. Am J Vet Res 1982;42:1371–1375.

10. Nien C, Flynn K, Chang M, et al. Reducing peak cornealhaze after photorefractive keratectomy in rabbits: pred-nisolone acetate 1.00% versus cyclosporine A 0.05%. J Cat-aract Refract Surg 2011;27:937–944.

11. Barton M. Equine keratomycosis. Compendium. 1992;14:936–950.

12. Bourcier T, Borderie V, Forgez P, et al. In vitro effects ofdexamethasone on human corneal keratocytes. Invest Oph-thalmol Vis Sci 1999;40:1061–1070.

13. Hendrix D, Ward D, Barnhill M. Effects of anti-inflamma-tory drugs and preservatives on morphologic characteristicsand migration of canine corneal epithelial cells in tissueculture. Vet Ophthalmol 2002;5:127–135.

Fig. 9. Severe inflammation and pain accompany stromalabscessation.



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