There is a large amount of diseases associated with the development of uveitis. Therefore, finding the exact cause that could be causing the inflammation can be a lengthy process. The three most important steps in developing a good differential diagnosis and finding the cause of uveitis are: gathering a very detailed history, ocular examination and an evaluation of all body systems. Labs, X-rays or tests may also be part of the medical evaluation and are frequently referred in cases of uveitis. Because many of the diseases associated with ocular inflammation can be diagnosed clinically, medical practice has not established a set of tests that should be referred as a standard protocol in cases of uveitis. For this reason, the selection of laboratories, examinations and/or radiographs is done in a complementary manner and according to the following criteria: location of the inflammation, history and clinical picture of the patients.
The utility of laboratories, examinations and radiographs is variable in many cases of uveitis. Some may yield information to diagnose the cause of the inflammation, but most are used as a complementary measure to the symptomatology and clinical findings. Laboratories are not a foolproof tool for finding the cause of uveitis, as many of the associated diseases can be diagnosed by medical evaluation alone. However, they are still an important tool in the evaluation of cases of uveitis that require it. The purpose of laboratories, examinations and/or radiographs is to rule out possible diseases that could be involved in the inflammatory process in order to choose the most appropriate treatment. Some results could end up identifying a systemic disease involved or offer valuable information for the prognosis of the case.
Most of the labs ordered initially are those that could successfully rule out possible leading causes of uveitis. These are not protocol-established labs, but are part of the established clinical guidelines for the management of uveitis. However, it is not unusual for these to be negative, since most cases of uveitis are idiopathic. Still, this information allows the physician to rule out primarily infectious causes and choose the most appropriate treatment. If the uveitis recurs, referral to other labs that may help identify the association of a systemic autoimmune disease is usually considered. However, this will depend on factors such as: the patient's clinical picture, cost, availability and the specificity of each particular laboratory.
Patients who experience a first episode of anterior uveitis without symptoms associated with systemic disease and who can be easily controlled with topical treatment usually do not require laboratory referral. If anterior uveitis recurs and the patient begins to present with symptoms associated with systemic disease, referral should be performed. In contrast, evaluation of cases of intermediate or posterior uveitis, especially if they are recurrent or present inflammation in essential ocular structures, is usually accompanied by examinations, laboratories and/or radiographs.
Some of the labs that are often referred in cases of ocular inflammation are:
Blood count, general biochemistry and erythrocyte sedimentation rate (ESR)
They help identify active systemic infections, parasitic infections, leukemia, immune status and general health status of the patient.
ANAs may be useful in pediatric cases of uveitis, especially if juvenile idiopathic arthritis is suspected. In contrast, their usefulness is variable in adults with uveitis, unless they present with some of the following: scleritis, recurrent anterior uveitis and/or have been diagnosed with rheumatoid arthritis. The usefulness of ANAs to diagnose systemic lupus erythematosus (SLE) is variable and their result should be used to support its clinical diagnosis. On the other hand, ANCAs could be referred in cases of anterior uveitis in which there is suspicion of granulomatosis with polyangiitis (Wegener's disease) or polyarteritis nodosa. Patients experiencing symptoms associated with rheumatoid arthritis may be referred for rheumatoid (RF) testing.
ECA and Lysozyme
ECA and Lysozyme are ltests with low specificity that are mostly used to support findings of granulomatous diseases, such as sarcoidosis. For this reason, their usefulness as a diagnostic tool is variable and should be used only as a complementary source to clinical findings.
Histocompatibility antigens
Some histocompatibility antigens are associated with a predisposition to develop certain diseases. That is, laboratories to detect these antigens are not used to make definitive diagnoses. The presence of one of these markers does not mean that the patient has the disease and there are patients who may have the disease even in the absence of the marker. For example, a patient with Behcet's disease may NOT have the HLA-B51 antigen while a person with this antigen may never develop the disease. Similarly, it is estimated that half of the cases of acute anterior uveitis are associated with the HLA-B27 antigen. However, a person can have this marker and still never develop uveitis.
HLA-DRB1*0102: Tubulointerstitial nephritis syndrome and uveitis
Specific serologies
The most frequently referred serological tests in almost all cases of uveitis are: syphilis, HIV and tuberculosis. This is done preventively since these diseases can produce inflammation in all parts of the eye: anterior, intermediate, posterior and diffuse (panuveitis). These three tests are very useful because they can easily diagnose the disease, are inexpensive and easy to perform. It should be noted that these laboratories are referred even if the patient is NOT at risk of having contracted any of these diseases (syphilis, HIV or tuberculosis). For this reason, the referral from these labs SHOULD NOT BE a source of concern for the patient or their loved ones. If you are concerned about this or any other reason, you may want to read the following article titled Emotional toll of uveitis.
Human Immunodeficiency Virus (HIV)
Syphilis
Toxoplasma
Toxocara
Tuberculosis
Rickettsia (Q fever)
Borrelia (Lyme disease)
Brucella
Leptospira
Chlamydia (reactive arthritis)
Cytomegalovirus (CMV)
Herpes Simplex (HSV I, HSV II)
Hepatitis panel
Epstein-Barr virus
Varicella Zoster Virus (VZV)
Skin tests
Of the following skin tests, tuberculosis (PPD) is most frequently referred. In addition, this test is required before starting treatment with immunomodulators. On the other hand, pathergy test could be ordered to support a clinical diagnosis of Behçet's disease.
Tuberculosis (PDD)
Histoplasmosis
Coccidioidomycosis
Pathergy test (Behçet's disease)
Sarcoidosis
Radiodiagnostic tests
Chest X-ray and magnetic resonance imaging (MRI) are the most frequently referred tests in cases of uveitis. Other radiographs may also be referred to rule out the possibility of the following diseases:
Ultrasound biomicroscopy (UBM) - hypotony, cyclitic membrane, ciliary body detachment,
atrophy of ciliary processes.
X-rays may be useful in case of suspicion of any of the following diseases:
Sarcoidosis: chest x-ray
Toxoplasmosis: brain MRI (if evidence of ocular toxoplasmosis in an immunocompromised
patient)
Retinoblastoma: eye ultrasound, CT scan and MRI of head and orbits
Multiple sclerosis: brain MRI
Occult intraocular foreign body: CT scan
Other tests
Other tests should be considered in recurrent or chronic cases of idiopathic uveitis. Consultation between physicians of different specialties is also recommended.
Colonoscopy - inflammatory bowel diseases and Behcet's disease
Urinalysis - suspected tubulointerstitial nephritis and uveitis syndrome (TINU), granulomatosis with polyangiitis (Wegener's Granulomatosis), systemic lupus erythematosus lupus (SLE).
Hearing test - suspicion of Vogt-Koyanagi-Harada syndrome (VKH) or sarcoidosis.
Hypercoagulability panel (ACA, LAC, favor V Leiden mut) - symptoms of occlusive vasculitis.
PCR of aqueous or vitreous humor - suspicion of necrotizing retinitis, toxoplasmosis, HSV, VZV, CMV
Tests that are usually ordered according to the anatomic location of the inflammation:
Anterior uveitis
CBC with differential
ANA
ANCA/RF/CCP
HLA-B27
VDRL, RPR, FTA-ABS, MHA-T, TP-PA
ESR
Urinalysis
Urine beta-2-microglobulin + serum creatinine
Antistreptococcal lysin O serology
PPD, QuantiFERON
HIV
Chest X-ray
Intermediate uveitis
CBC with differential
VDRL, RPR, FTA-ABS, MHA-TP, TP-PA
Serum angiotensin converting enzyme
Lysozyme Serum
ESR
Urinalysis
Urine beta-2-microglobulin + serum creatinine
Lyme antibody testing (ELISA + Western-Blot)
VDRL, RPR, FTA-ABS, MHA-TP, TP-PA
Toxoplasma serology
Toxocara serology
PPD, QuantiFERON
Cerebrospinal fluid analysis (if suspicious for multiple sclerosis)
HIV
Chest X-ray
Posterior uveitis
CBC with differential
Serum angiotensin converting enzyme
Toxoplasma serology
Toxocara serology
VDRL, RPR, FTA-ABS, MHA-TP, TP-PA
B. henselae serology
B. burgdorferi serology
West Nile Virus Serology
PPD, QuantiFERON
HIV
Chest X-ray
Suspected masking syndrome:
CBC with differential
Additional tests according to the clinical case
Tests and labs ordered prior to starting immunomodulatory therapy
Before starting immunomodulatory therapy, it is important to rule out the presence of any infection. For that reason, some labs that are ordered before starting immunomodulatory therapy are: CBC with differential, tuberculin test (PPD and/or QuantiFERON), hepatitis panel, HIV test, MRI of the brain, and/or chest ×-ray. The presence of any fungal infection in the body (skin, hair, nails) is also checked. In addition, it is extremely important to rule out the possibility of a demyelinating disease, such as multiple sclerosis, before starting treatment with biologic agents. Finally, once immunomodulatory treatment begins, your physician will order follow-up labs from time to time to check your health status.
Follow-up tests and labs for patients under immunomodulatory treatment
Once the treatment with immunomodulators is implemented, doctors order some follow-up tests and laboratories to progressively evaluate the patients' health. These are performed every few months, depending on the type of medication:
Eye health and vision can be evaluated with the use of multiple simple tests performed in the doctor's office. The most important are: visual acuity test, intraocular pressure measurement (tonometry), slit lamp and indirect ophthalmoscope observation of the eyes. The other examinations and tests are also important, but they are performed in a complementary manner according to the medical evaluation.
Visual acuity (Snellen)
It is a simple, non-invasive test that provides information about the patient's visual ability.
Tonometry
A noninvasive test to measure intraocular pressure. One of the ways to perform this test is by administering anesthetic drops to the eyes and placing a tonometer gently over the cornea.
Campimetry (field of view)
Non-invasive test to evaluate the patient's peripheral vision.
Ophthalmoloscopy: slit lamp, gonioscopy, direct or indirect ophthalmoscopy
Non-invasive examinations that allow observation of the inside of the eyes. The slit lamp is the most important instrument for ophthalmologists.
Optical Coherence Tomography (OCT)
A non-invasive, high-magnification test to observe conditions of the retina, macula and other structures. It is also used to monitor the effectiveness of treatments.
Angiography: fluorescein angiography and indocyanine green angiography
Tests used especially to evaluate cases of posterior uveitis. Provides information on possible retinal complications such as: macular cystic edema (CME), retinal or choroidal neovascularization, vasculitis, leakage, occlusive vasculopathy, etc. It helps to identify blood vessel leaks or to evaluate the retinal pigment epithelium
Background autofluorescence
A test used to evaluate the status of the retinal pigment epithelium. It is especially useful in cases of white spot syndromes, among other pathologies.
Photograph of the inside of the eyes (fundus)
A noninvasive test used to take pictures of the retina. Helps identify lesions and assess intraocular health.
Electroretinography
Angiograms and/or electroretinographies are usually used in cases of uveitis presenting retinal vasculitis or uveitis associated with white spot syndromes.
Ultrasonography
Exam used to evaluate the posterior segment when vitreous pacification is present.
Stereopsis
Non-invasive test used to observe the patient's visual ability to perceive depth.
Ishihara
A simple, non-invasive test that allows us to observe the patient's color perception ability.
Potential Visual Acuity Meter (PAM)
It is a non-invasive test used to predict visual acuity prior to surgery. It is used when there is cataract or other problems in the anterior part of the eyes.
Amsler Grid test
Non-invasive test to inspect the visual field of patients, especially alterations in central vision.
Pachymetry
A simple test used to measure the thickness of the cornea.
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