Tests and diagnosis of Uveitis

The slit lamp examination must be performed by an ophthalmologist to assess the condition of the anterior segment of the eye. Inflamed eyes often present aggregates of inflammatory cells on the posterior side of the cornea (subendothelial keratic precipitates). The presence of inflammatory cells (Tyndall effect) and proteins (aqueous flare) in the aqueous humour is indicative of a broken blood-aqueous barrier and can be indirectly correlated to the degree of inflammation. Inflammation is graded from 0 to 4+ according to the intensity.

When there are a lot of inflammatory cells in the anterior chamber they form a fluid deposit known as a level of hypopyon (pus). One of the common complications associated with uveitis is the formation of anterior or posterior synechiae (when the iris adheres to the iridocorneal angle or crystalline lens, respectively). If there is inflammation in the intermediate or posterior segments of the eye, then inflammatory cells may be observed in the vitreous, a phenomenon known as vitritis or vitreous Tyndall.

The degree of vitritis can also be graded from 0 to 4+. An eye fundus examination is essential in all inflammatory processes of the eye and is performed with either a direct or indirect ophthalmoscope and the aid of lenses. The exam must be done by trained specialists and is usually carried out by an ophthalmologist.

Ophthalmoscopy helps differentiate lesions in the retina or choroid, such as focal areas of inflammation or necrosis, or signs of retinal vasculitis, and determine whether or not the optic nerve is affected. Depending on the location of the inflammatory focus the condition can be classified as retinitis (in the retina), choroiditis (choroid), chorioretinitis (choroid + retina) or neuroretinitis (optic nerve + retina).

Given that uveitis is a group of complex diseases that affect not just the eyes but other organs as well, ophthalmologists specialising in uveitis often collaborate with other specialists to reach a joint diagnostic and therapeutic approach. This multidisciplinary collaboration could be a permanent team in a “multidisciplinary uveitis unit” formed by an ophthalmologist, internist, rheumatologist, immunologist, neurologist, infectious disease specialist, etc.

There is no standard battery of tests that must be carried out on all patients affected by uveitis. The approach is normally adapted to the most likely causes in function of each patient’s clinical picture. Most patients require one or a few diagnostic tests. Nevertheless, when the background and physical examination do not reveal the cause of the uveitis, then the specialists propose a group of basic tests, such as a complete blood count, erythrocyte sedimentation rate (ESR), syphilis serology and a chest X-ray.

• Blood count, overall biochemistry and erythrocyte sedimentation rate (ESR). These are low-cost tests that provide objective data about the patient’s general condition and immune status.
• Antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCAs), antiphospholipid antibodies. ANA tests are helpful whenever juvenile idiopathic arthritis, Sjögren’s syndrome, systemic lupus erythematosus or other connective tissue diseases are suspected. ANCA tests may be requested in the context of scleritis or peripheral ulcerative keratitis, regardless of whether or not it is associated with uveitis. There are two types of ANCA test: altered antibodies in Wegener granulomatosis (c-ANCA) and increased antibodies in polyarteritis nodosa (p-ANCA).
• ACE and lysozyme. May be altered in cases of sarcoidosis, although both are rather non-specific and of limited value.
• Histocompatibility antigens. HLA-A29 (birdshot retinochoroidopathy or birdshot disease), HLA-B27 (ankylosing spondylitis, reactive arthritis or Reiter’s syndrome, psoriatic arthritis, arthritis associated with IBD), HLA-DR5 (oligoarticular juvenile idiopathic arthritis), HLA-B51 (Behçet’s disease). Around 50% of patients with anterior uveitis are HLA-B27 positive. Additionally, acute anterior uveitis takes on some special characteristics in HLA-B27 positive patients: earlier age of onset, generally affects males, recurrent with reappearances alternating between eyes, more intense episodes and a greater incidence of complications.
• Specific serological tests. Lues, HIV, toxoplasma, toxocara, Rickettsia (Q fever), Borrelia (Lyme disease), Brucella, Leptospira, Chlamydia (reactive arthritis), human herpesvirus, Epstein-Barr virus, cytomegalovirus, etc. The most useful serological tests are those for syphilis and HIV. Others should be considered in function of the diagnostic suspicion in the context of the ocular and systemic symptoms.
• Skin tests. Tuberculosis, histoplasmosis and coccidioidomycosis can be identified by means of skin tests. The Mantoux or PPD test is the most commonly used test and it can help determine the presence of tuberculosis. It should be requested in the presence of pulmonary symptoms, known exposure, refractory cases with a compatible pattern, suspicious chest X-ray, ocular symptoms compatible with tuberculosis, and always before administering long-term immunosuppressive therapy or biologic medicines.
• Diagnostic radiology. Chest X-ray, sacroiliac joint X-rays, CT, MRI, gallium scintigraphy.
• Other tests. Spinal tap, skin biopsy, blood culture, intraocular fluid study, cross-consultation with other specialists.