Idiopathic Anterior Uveitis

Classification of Uveitis

One of the most important steps in making a diagnosis in a patient with uveitis is to become familiar with the terminology of the Standardization of Uveitis Nomenclature (SUN) ( Table 103.1 ). Each individual case should be classified at least based on anatomic location of inflammation, as some conditions may have a typical pattern of presentation. For example, a patient with ankylosing spondylitis is more likely to develop acute unilateral, anterior uveitis, whereas a patient with multiple sclerosis is more likely to present with chronic bilateral intermediate uveitis. However, some conditions, such as sarcoidosis, may initially present as anterior uveitis and then progress to panuveitis.

Additionally, uveitis may be classified based on its onset, duration, and course of disease. For example, uveitis related to human leukocyte antigen (HLA)-B27 positivity tends to occur with a sudden onset and limited duration. In contrast, sympathetic ophthalmia generally causes chronic, persistent inflammation that is frequently refractory to treatment.

One may use clinical pathologic terms to categorize uveitis into granulomatous and nongranulomatous types. The terms are misnomers, as they are not derived from actual pathologic study. Clinically, granulomatous uveitis is associated with at least one of the following: large mutton-fat keratic precipitates (KPs), iris nodules, and choroidal granuloma. Examples of the conditions that may cause such findings are uveitis associated with sarcoidosis, tuberculosis, Vogt-Koyanagi-Harada (VKH) syndrome, sympathetic ophthalmia, multiple sclerosis, syphilis, bacterial or fungal endophthalmitis, lens-induced uveitis, and retained intraocular foreign body (IOFB). However, the size of the KPs may vary depending on the severity of inflammation. For example, low-grade sarcoid uveitis may present with small KPs. In contrast, diseases that usually cause clinically nongranulomatous findings, such as HLA-B27–related anterior uveitis, may rarely present with large mutton fat–like KPs in eyes with severe inflammation.

Although no single parameter is adequate to categorize uveitis syndromes, utilization of the available classifications will usually guide clinicians in the correct diagnostic direction.

History of Uveitis

One of the most important steps in the diagnosis and treatment of patients with uveitis is thorough history taking. The chief complaint and history of present illness often direct the differential diagnosis. A careful review of systems may reveal a possible etiologic association. Uveitis questionnaires can be used successfully in the majority of patients. The review of neurologic (including eyes, ears, nose, and throat), cardiovascular, pulmonary, gastrointestinal, genitourinary, hematologic, endocrine, integumentary, and musculoskeletal systems should be included.

Many patients referred to ophthalmology may already have a systemic diagnosis or other clinical clues important for treatment. For example, a patient with Crohn disease who develops a red and painful eye may suffer anterior uveitis, scleritis, or peripheral ulcerative keratitis; having pets at home is relevant for a diagnosis of parasitic infestation; an African American woman with a family history of respiratory problems may have sarcoidosis; traveling to endemic areas may involve exposure to specific infectious agents; a patient with poorly controlled diabetes may not tolerate high-dose systemic corticosteroids; and a patient with a history of alcohol abuse would not be a good candidate for the use of methotrexate. Therefore the patient’s personal medical/surgical as well as family and social history should be vigilantly reviewed.

Ocular Examination

Visual acuity (VA), pupillary reaction, and intraocular pressure (IOP) in ophthalmology may be comparable to vital signs in internal medicine. Pinhole acuity can be improved in most patients with refractive errors but may be unimproved in those with macular diseases. Pupillary reaction should be monitored prior to dilation. Irregular pupillary shape may indicate posterior synechiae or iris atrophy. Penlight examination for relative afferent pupillary defects is always essential. Conjunctival and scleral injection as well as iris color are best observed under white room light. The presence of iris heterochromia can easily be missed by a slit lamp exam. Corneal sensation should be tested prior to administering topical anesthetic drops, especially in patients with unilateral uveitis or scleritis that may be caused by herpetic infection. Extraocular motility can be limited in those with associated orbital inflammation.

Slit lamp examination of the eye and adnexa is crucial. Skin lesions on eyelids may be related to ocular inflammation—for example, herpetic infection. Eyelid chancre is a sign of primary syphilis. Whitening of periorbital skin (vitiligo) and eyelashes (poliosis) in a young patient may suggest a diagnosis of VKH. Follicular conjunctival reaction may be present in patients with uveitis associated with follicular conjunctivitis, such as a viral infection or medicamentosa from topical brimonidine. The palpebral conjunctiva should be everted to search for conjunctival nodules as well as for signs of lacrimal gland enlargement in those suspected of having sarcoidosis. Patients with uveitis commonly present with KPs on the corneal endothelium. The size and pattern of the KPs may help to narrow down the differential diagnoses. Large mutton-fat KPs may indicate granulomatous uveitis, as previously discussed. Diffuse stellate KPs may be seen in Fuchs heterochromic iridocyclitis. Herpes simplex can result in KPs outside the usual location within the Arlt triangle. Interstitial keratitis may imply infectious causes or Cogan syndrome. Peripheral ulcerative keratitis can be associated with immune-mediated rheumatologic conditions.

The activity of anterior uveitis is proportional to the quantity anterior chamber cells. Table 103.2 depicts the universally accepted grading system from the SUN Working Group. Anterior chamber flare generally reflects chronicity but may not parallel disease activity. Extra care may be required on examination to detect small iris nodules. Iris atrophy can be identified by using the retroillumination technique, which is particularly important in diagnosing herpetic iritis and posterior iris chafing syndrome from malposition of an intraocular lens. Minimally retained lens materials after cataract surgery may be identified under gonioscopy. Fluorescein staining should be performed after anterior segment examination, as fluorescein can interfere with an evaluation of the aqueous flares.

Examination of the lens is also crucial; in cases of chronic postoperative endophthalmitis, plaques may be present on the surface of the intraocular lens or within the capsular complex, and capsular block (or capsular bag distention) syndrome can occur in conjunction with anterior uveitis.

The number of vitreous cells is not an accepted indicator of active inflammation, since vitreous cells are generally present for a long time after the improvement of inflammation. Quantifying white cells in the mid- or posterior vitreous is technically difficult. The quantification of vitreous haze is frequently substituted as a measure of active inflammation in the vitreous humor. Vitreous haze, however, can be affected by the clarity of the lens and is dependent on the light intensity used in the examination. The reproducibility of vitreous haze as an index of inflammation has been questioned. Full funduscopic examination should be performed to exclude posterior pathology. Scleral depression is generally required to identify pars plana exudates in some cases of intermediate uveitis.

Optical coherence tomography (OCT) is crucial to diagnose subtle macular changes, particularly cystoid macular edema (CME). It is also a useful tool to monitor the response to therapy. Fundus autofluorescence imaging and fluorescein angiography are essential, especially in cases with chorioretinopathy and retinal vasculitis.

Differential Diagnoses of Anterior Uveitis

Detailed history taking and careful examination are essential to developing an appropriate differential diagnosis. When cell-like structures are observed in the anterior chamber, one should ask, “Does the sign truly represent inflammation?” The small particles that float in the anterior chamber can also be structures other than inflammatory leukocytes. Table 103.3 lists examples of noninflammatory conditions that may simulate anterior uveitis.

Table 103.4 depicts examples of the conditions that can cause isolated anterior uveitis. These possible etiologies should be excluded prior to classifying a disease as “idiopathic” uveitis. The majority of the exclusion can be accomplished after comprehensive interview and examination. Some conditions can cause intermediate uveitis or panuveitis but may start with anterior uveitis or present with prominent inflammation of the anterior chamber ( Table 103.5 ).

When such inflammation accompanies peripheral ulcerative keratitis or scleritis, it may point to possible rheumatologic conditions ( Table 103.6 ) and less commonly to infectious origins. Bisphosphonate toxicity can cause scleritis and uveitis simultaneously.