Uveitis specifically refers to inflammation of the middle layer of the eye (the uveal tract) but more commonly, it may refer to any inflammatory process involving the interior of the eye, with inflammation specifically of the uvea termed iridocyclitis.

Anatomy/Physiology

The uvea is the vascular and muscular tunic of the eye composed of the iris, ciliary body, and choroid. Because of its rich blood supply and proximity to other vital intraocular structures, the uvea is involved in most intraocular disease processes. The iris and ciliary body together comprise the anterior uvea. Normal pupillary function (and retinal integrity) are evaluated through assessment of the pupillary light reflexes (PLRs). The ciliary body has two primary functions. It is responsible for production of aqueous humor vital for nourishment of the anterior segment of the eye. Also, contraction of the ciliary body and subsequent changes in lens zonular tension are necessary for accommodation (change in shape) of the lens. The posterior uvea, or choroid, supplies nourishment to the outer layers of the retina.

Clinical Signs and Diagnosis of Uveitis

Inflammation of the anterior uvea is termed anterior uveitis or iridocyclitis, and inflammation of the posterior uvea is termed posterior uveitis or choroiditis. Inflammation of the entire uveal tract is called panuveitis. Failure to distinguish uveitis from other ocular diseases may result in insufficient or inappropriate therapy with the most disastrous sequelae being continued ocular pain, blindness, or progression of undiagnosed systemic disease. The ocular signs of anterior uveitis are variable and may mimic other ocular diseases.

A few of the more common ocular changes and techniques for identifying them are presented:

 Excessive tearing, squinting, or photophobia are all readily ascertained by visual inspection of the animal and suggest varying degrees of ocular discomfort.

 A "red eye" is one sign of uveitis. The term ciliary flush refers to injection of the deep perilimbal anterior ciliary vessels and is common with uveitis. Ciliary flush can be distinguished from the diffuse conjunctival hyperemia more common with extraocular disease, but both types of vascular injection are often present with uveitis. Many causes of a "red eye" exist other than uveitis, and the most notable differential diagnoses should include dry eye (KCS), ulcerative keratitis, or glaucoma. In short, a "red eye" with normal or excessive tear production, negative fluorescein stain retention, and low intraocular pressure is likely to have uveitis.

 Pupillary constriction, or miosis, occurs from inflammatory mediators in the eye acting directly on the iris sphincter muscle. Similar actions on ciliary body musculature cause a painful ciliary body spasm. Miosis may be more apparent when examining the eyes simultaneously in a darkened room under diffuse retroillumination with a penlight or Finoff transilluminator. Light reflected from the tapetal fundi by this technique allows ready detection of disparities in pupil size, or anisocoria. Chronic uveitis may cause adhesions of the iris to the anterior lens surface, or posterior synechia, resulting in an immobile or distorted pupil. The pupil of a uveitis eye may be slow to dilate following short acting mydriatic therapy (e.g., tropicamide) when compared with the normal eye, and this observation is itself diagnostic. Alternatively, the pupil may be dilated and non-responsive if secondary glaucoma has occurred from chronic uveitis.

 Aqueous flare refers to increased protein and cellular debris within the anterior chamber resulting from breakdown of the blood-uveal barrier. Focused light shone into the anterior chamber of such an eye creates the "Tyndall effect" which is often compared to that of shining a flashlight within a smoke filled room. Normally only two light reflections are seen, one on the cornea, and the other on the anterior lens surface. If the light reflections appear as a continuous light beam, the patient's eye has aqueous flare.

 Keratic precipitates (KPs) are accumulations of inflammatory cells adherent to the ventral corneal endothelium. KPs migrate to this location because of thermal convection currents within the eye. These may be readily missed during examination if one is not specifically looking for them. Their detection is facilitated by magnification (such as a head loupe) and by gently tilting the animal's head downward, thereby allowing upward rotation of the eye and ready examination of the ventral cornea. The presence of KPs always indicates active or prior uveitis.

 Decreased intraocular pressure (IOP) is one of the earliest and most subtle indications of uveitis. Although the IOP is usually low, it will vary depending on the duration and/or severity of uveitis. If uveitis is intense enough or persists for sufficient time for inflammatory debris to obstruct the filtration angle or seclude the pupil, then secondary glaucoma may occur (refer to Glaucoma notes). Differences in IOP of 5 mm Hg or greater between two eyes, even if values obtained are in the absolute normal range, should be considered significant and suggests the eye with the lower IOP has uveitis.

 Corneal edema may also occur with uveitis, for which the primary differential diagnoses are glaucoma and corneal endothelial dystrophy. Antigen/antibody complexes and/or inflammatory debris adherent to the corneal endothelium are responsible for the edema of uveitis. Although not commonly seen anymore, anterior uveitis following vaccination with type-1 adenovirus, the so-called "blue eye", derives its name from severe corneal edema. IOP determination will distinguish the corneal edema of uveitis from that of glaucoma, although the two conditions may occur together.

Pathogenesis of Uveitis

Uveitis is often a clinical sign of a much greater or widespread disease process. The globe has virtually no lymphatic drainage, and the uvea subserves this function by acting as an accessory lymph node. Virtually any foreign antigen (infectious or otherwise) may pass transiently through the uvea with potential to damage uveal tissue and/or incite an immune response, thus causing uveitis. Besides infectious agents, other causes include neoplasia, autoimmune disease, trauma, and reaction to endogenous antigen, such as lens protein. Ulcerative keratitis causes varying degrees of uveitis but does so through a localized "axonal reflex". The clinical signs of uveitis are due to disruption of the blood-uveal (or blood-aqueous) barrier and release of various chemical mediators following tissue damage. Uveal damage causes exudation of plasma proteins, inflammatory cells, and inflammatory mediators, most notably prostaglandins, leukotrienes, histamine, and neurotransmitters such as substance-P. Permanent alterations in uveal vascular structure and/or permeability may occur, and such changes have been implicated as one cause for recurrent episodes of uveitis.

Diagnosis of Uveitis

When the diagnosis of uveitis is made, one should strive hard to identify the cause. The potential causes of uveitis are limitless, and a causative factor is unfortunately not identified in many cases. The clinician must choose between extensive diagnostic evaluation for uveitis and associated client expense versus that of only symptomatic therapy.

A thorough history and general physical examination are indicated in all cases of uveitis. A complete blood count, serum biochemical profile, urinalysis, and thoracic radiographs are recommended as minimum screening for uveitis cases where systemic disease is suspected. The selection of additional diagnostic tests are dictated by additional physical findings and knowledge of diseases endemic to a given practice area. Bilateral anterior uveitis and unilateral or bilateral panuveitis with retinal involvement are highly suggestive of systemic disease. However, animals with systemic disease may occasionally present with only unilateral uveitis.

Cytologic evaluation and bacterial or fungal culture of aqueous humor, vitreous or subretinal aspirates may be beneficial in diagnosing uveitis. Aqueous centesis is performed following general anesthesia and utilizing a tuberculin syringe and 25- or 27-gauge needle directed into the anterior chamber through the lateral corneoscleral junction (limbus). In patients with posterior uveal involvement, vitreous aspiration may also yield positive results. Following anesthesia, a 22-gauge needle is directed posteriorly through the pars plana of the ciliary body approximately 6 mm posterior to the lateral limbus. In cases of retinal separation, subretinal aspiration is similarly performed but the needle is passed through the sclera and then into the subretinal space. Vitreous or subretinal aspirates are reserved for eyes with marked vitreous opacity or exudative retinal detachments. Care must be taken not to puncture the lens or induce intraocular hemorrhage during aspiration of aqueous, vitreous or subretinal fluid.

Treatment

In cases of uveitis, topical anti-inflammatory therapy should be instituted immediately in an attempt to avoid irreparable damage to the eye(s). Systemic anti-inflammatory therapy requires greater discretion. Therapy will often include various combinations of anti-inflammatory, mydriatic/cycloplegic, antimicrobial or additional therapy as determined by the presence or suspicion of a systemic disease. Topical therapy may suffice for mild to moderate anterior uveitis, but severe anterior uveitis and posterior segment disease require systemic therapy. When a specific cause is identified, therapy should be modified to treat the underlying disorder. We will discuss in lecture when and what types/routes of the following therapeutic agents are appropriate for cases of uveitis when secondary glaucoma is present.

Corticosteroids

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Mydriatic/cycloplegic drugs

Antimicrobial therapy

Miscellaneous agents (i.e., azathioprine)

References

References are available upon request.