Cat with a Cloudy Eye

Norris is sent home on prednisolone acetate 1% ophthalmic suspension (1 drop in the left eye 4 times a day) and atropine ophthalmic ointment (quarter-inch strip on the left eye 2 times a day). At the 1-week recheck, Norris shows no improvement (and possible worsening) of clinical signs. Intraocular pressure (IOP) of the left eye has increased from 8 to 18 mm Hg. Additionally, the owners have noted inappetence and general lethargy. You perform a urinalysis using the urine collected at home (Table 2) and recommend further diagnostics; the owners consent.

Idiopathic uveitis is a common presentation in cats, with a reported incidence of 37% to 70%.^1-3 Diagnosis can be made only after excluding other ocular or systemic causes; however, empirical or supportive treatment for uveitis is often instituted because of the cost or time restraints of ruling out causative disease.

The goals of treatment are to stabilize the blood-aqueous barrier, control pain, and prevent secondary complications (eg, glaucoma). Glaucoma results from accumulation of inflammatory cells, fibrin, and other debris in the iridocorneal angle; this causes decreased outflow of aqueous humor.⁴ Posterior synechiae from uveitis also can prevent outflow of aqueous humor through the pupil and cause glaucoma and iris bombé.

Mydriatics are useful in preventing synechiae and aid in pain control by reducing ciliary body spasm. Tropicamide and atropine are commonly used mydriatic agents, but tropicamide is less commonly employed for cycloplegia because most of its action is at the iris dilator muscle as opposed to the ciliary body.⁵ Likewise, tropicamide’s effect in pupil dilation is blunted by the presence of uveitis, wherein prostaglandins bind to receptors in the iris sphincter muscle, resulting in miosis. Atropine is a more potent cycloplegic and mydriatic with a longer duration of action; therefore, its use is preferred for uveitic eyes.^5,6

Related Article: Anterior Uveitis

Care should be taken to monitor corneal health and IOP; use of parasympatholytics may cause a decrease in tear production,⁷ and use of mydriatic and cycloplegic agents has been associated with an increase in IOP.^8,9 Immunosuppressive medications can cause recrudescence of latent feline herpesvirus 1 with subsequent corneal ulceration. Additionally, dilating agents can occasionally induce profound salivation, as the drug flows through the nasolacrimal system and is licked by the cat as it exits the nose. Use of an ointment rather than drops may ameliorate this side effect.

Corticosteroids (topical or oral) can be used for immunosuppression, inhibition of arachidonic acid metabolism, antifibrotic therapy, and inhibition of neovascularization. Prednisolone acetate, although less potent than dexamethasone, is formulated to have better penetration and is therefore preferred over dexamethasone. Topical treatment with steroids is ideal to limit systemic effects and has not been shown to exacerbate systemic disease.¹⁰ Contraindications include presence of a corneal ulcer or active superficial infection. Topical NSAIDs (eg, diclofenac, flurbiprofen) may be used if ulceration is present, but these alone may be insufficient in controlling active uveitis. Dosing frequency will typically correlate with uveitis severity (eg, every 6 hours for 2+ flare, every 6-8 hours for trace-1+) and can be tapered accordingly as uveitis subsides.

Setting an appropriate recheck period is an important part of managing uveitis, as it allows for assessment of patient response to treatment and of secondary complications. If uveitis improves, anti-inflammatory drugs can be continued until the eye is free of clinical signs, at which point the drugs can be slowly tapered. Mydriatics can be continued until the pupil is dilated and then tapered to the lowest dose necessary to maintain effect. The owners should be prepared for what to expect if uveitis does not improve or if systemic disease goes undiagnosed. They should also be made aware that long-term therapy may be needed.

Related Article: Top 5 Glaucoma Drugs

Despite anti-inflammatory and mydriatic therapy, secondary glaucoma is beginning to develop in Norris’ eye. Although 18 mm Hg is within normal range, uveitic eyes are expected to be hypotensive¹¹; therefore, secondary glaucoma should be suspected if the IOP in a uveitic eye is in the normal or high-normal range, and pre-emptive treatment for glaucoma should be considered with regular monitoring of IOP. 

If treatment for secondary glaucoma is instituted, prostaglandin analogues (eg, latanoprost) should be avoided, as they are potent miotics and may not be effective in reducing IOP in cats.¹² In the authors’ experience, carbonic anhydrase inhibitors (eg, dorzolamide) or ß-blockers (eg, timolol) are more effective in reducing IOP in cats. Most importantly, the primary disease or uveitis should be adequately addressed to improve IOP.

Lack of response to reasonable anti-inflammatory treatment should increase the suspicion for more significant disease underlying the uveitis and can be the basis for recommending further diagnostics. If the owners decline further diagnostic investigation, options typically include increasing the frequency of topical medications or treating with systemic anti-inflammatory drugs, with the caveat that systemic disease could be made worse by oral steroids or NSAIDs.

Therapeutic treatment for uveitis is appropriate, as therapy for the eye is important for quality of life. However, further testing should also be recommended in case systemic disease is present. If the owners decline further diagnostic testing, they should be informed of the risk for missing potentially significant or treatable disease that could affect the patient’s long-term prognosis. Basic bloodwork and urinalysis, along with testing for common infectious diseases, are a good starting point.

Because of Norris’ age, you recommend medical imaging bloodwork to rule out additional disease.

Thoracic radiography is within normal limits, but abdominal radiography shows marked renomegaly of both kidneys, with noted irregular borders and shape of the kidneys (Figure 2). Abdominal ultrasonography shows a hyperechoic, irregular kidneys (Figure 3). You perform ultrasound-guided fine-needle aspiration of the left kidney, which contains lymphoid and lymphoblast cells (Figure 4).

Norris is diagnosed with primary renal lymphoma and secondary uveitis. The owners elect to pursue chemotherapy.

Although idiopathic uveitis is common, uveitis may be secondary to systemic disease. With anterior uveitis, time and financial costs often complicate diagnosis of idiopathic or immune-mediated (ie, lymphoplasmacytic) disease. Concurrent posterior segment disease (eg, chorioretinitis) should increase suspicion for underlying systemic disease but may be difficult to appreciate. Extensive testing and imaging may be required to diagnose idiopathic disease. 

Infectious causes of anterior uveitis can include FeLV, feline infectious peritonitis, FIV, Toxoplasma spp, Cuterebra spp infestation, fungal infection (eg, Histoplasma spp, Cryptococcus spp, Coccidioides spp), and Bartonella spp. Clinical intuition, geography, and presentation can guide prioritization of infectious disease testing; results should be interpreted according to estimated positive or negative predictive value.¹³

Related Article: Feline Lymphoma

Trauma can be a direct cause of uveitis in cats and is usually witnessed or inferred by patient history. 

Systemic treatment with anti-inflammatory drugs (eg, systemic prednisolone, NSAIDs) can usually be safely instituted these cases. Patients with penetrating trauma should receive concurrent antibiotic therapy with a recommendation for surgical repair, if indicated. For cats that lose vision, enucleation is recommended (even if the eye is comfortable) because of the risk for posttraumatic ocular sarcoma.¹⁴ These sarcomas are generally aggressive and invasive and may break out of the eye into the orbit or travel up the optic nerve into the brain. Development can occur months to years after the initial injury.¹⁴

Neoplasia can affect the eye as a primary or metastatic condition. The most common primary neoplasia of the eye in cats is iridal melanoma; lymphoma is the most common metastatic tumor of the eye.^15,16 One study reported ocular involvement in 48% of cats with systemic lymphoma.¹⁷ Other ocular metastatic neoplasias include fibrosarcoma, squamous cell carcinoma, mammary adenocarcinoma, uterine adenocarcinoma, and other adenocarcinomas of unknown origin.¹⁵ 

Norris’ prognosis is poor. Treatment options and expected outcomes should be communicated with the clients. Lymphoma is a systemic disease, so chemotherapy is the treatment of choice; a multimodal approach shows the greatest opportunity for success.¹⁸ 

Supportive therapy for uveitis with topical anti-inflammatory drugs and mydriatics (as detailed in Case Route 1) should be started concurrently with chemotherapy. Treating the underlying lymphoma will typically result in improvement of secondary uveitis, unless there are secondary complications (eg, glaucoma) or chronic changes to the uveitic eye (eg, synechiae) that may persist.

Pursuing diagnostics at a more accelerated pace allows for earlier identification of underlying disease. This may allow for better treatment and prognosis. However, because of the prevalence of idiopathic disease, the owners should be informed of the possibility of negative tests. If idiopathic uveitis is confirmed, systemic treatment with anti-inflammatory drugs (eg, oral prednisolone) can be more safely instituted if the eye does not respond to topical medications alone.