Medical history, review of systems, thorough ophthalmologic and general physical examination, and formulation of a working differential diagnosis are cornerstones of the workup of a patient with uveitis. They should precede any laboratory testing. Laboratory testing is not a substitute for a thorough, hands-on clinical evaluation.
Most uveitis specialists do recommend syphilis testing for all uveitis patients, as syphilis can present as any form of uveitis, and systemic infection is often undiagnosed. In addition, the consequences of treating with steroid in the presence of untreated occult syphilis infection can be disastrous for patient outcomes. In the correct clinical scenario, or where immunomodulatory therapy (IMT) will be used, most uveitis specialists also recommend testing for tuberculosis with a purified protein derivative (PPD) skin test or interferon-gamma release assay. A chest radiograph can screen for sarcoidosis, which is a common cause of uveitis with protean manifestations. Tables 5-4 and 5-11 list some of the laboratory tests and their indications. Later chapters further discuss these tests in context of the various types of uveitis.
It is important to use caution in ordering and interpreting laboratory tests, because even very sensitive and specific tests are not perfect and can yield misleading results if the likelihood of disease in a particular patient is low. In other words, when testing a large group of patients for a very rare disease, a positive test may not actually represent the true presence of disease. The Bayes theorem describes this concept. The theorem is a statistical calculation used to describe the probability of an event based on prior knowledge of conditions that might be related to the event. (See BCSC Section 1, Update on General Medicine.)
Ophthalmic Imaging and Functional Tests
Ophthalmic imaging and functional testing are useful both diagnostically and in monitoring the patient’s response to therapy. They can provide information not obtainable from biomicroscopic or fundus examination. The use of combined imaging modalities, called multimodal imaging, can be complementary and additive in this task. For discussion of ophthalmic imaging modalities and electroretinogram testing, see BCSC Section 12, Retina and Vitreous.
Kawali A, Pichi F, Avadhani K, Invernizzi A, Hashimoto Y, Mahendradas P. Multimodal imaging of the normal eye. Ocul Immunol Inflam. 2017;25(5):721–731.
Van Gelder RN. Diagnostic testing in uveitis. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2013, module 4.
Optical coherence tomography
Optical coherence tomography (OCT) produces a series of high-resolution cross-sectional images of the retina and choroid and is used to identify morphologic changes seen in eyes with uveitis. A noncontact imaging technique, OCT has become the standard-of-care method for objective measurement of uveitic macular edema (Fig 5-9), retinal thickening, subretinal and intraretinal fluid associated with choroidal neovascularization, and serous retinal detachments. Although sometimes useful when the fundus is viewed in eyes with smaller pupils, media opacity can limit the clarity of OCT. OCT is also valuable in monitoring the nerve fiber layer in patients with uveitic glaucoma. Anterior segment OCT may be useful to evaluate an eye for retained lens fragments or IOL chafing in persistent postoperative uveitis. There are ongoing efforts to develop OCT-based objective grading of intraocular cells/inflammation.
Enhanced depth imaging OCT (EDI-OCT; Fig 5-10) provides deeper tissue penetration. This technique allows visualization of the choroid, which can have structural alterations in several uveitic diseases, notably Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and birdshot chorioretinopathy.
Table 5-11 Laboratory Tests and Imaging Studies Used in Uveitis Evaluations
OCT angiography (OCT-A) relies on repeated high-resolution scans of the same area to assess differences in blood flow, producing structural images of perfused vessels in ocular tissues. Case reports and case series describing the OCT-A characteristics of active and inactive chorioretinal lesions are emerging. These will have increasing implications for diagnosis and treatment of posterior uveitides over time.
Kim J, Knickelbein J, Jaworski L, et al. Enhanced depth imaging optical coherence tomography in uveitis: an intravisit and interobserver reproducibility study. Am J Ophthalmol. 2016;164:49–56.
Pichi F, Sarraf D, Arepalli S, et al. The application of optical coherence tomography angiography in uveitis and inflammatory eye diseases. Prog Retin Eye Res. 2017;59:178–201.
Figure 5-9 Optical coherence tomography image of uveitic macular edema in a patient with juvenile idiopathic arthritis–associated uveitis.
(Courtesy of Thellea K. Leveque, MD, MPH.)
Figure 5-10 Enhanced-depth imaging optical coherence tomography in a patient with Vogt-Koyanagi-Harada syndrome A, During quiescence with relatively normal choroidal thickness (arrows). B, During uveitis activity with diffuse choroidal thickening (arrows).
(Courtesy Thellea K. Leveque, MD, MPH.)
Fluorescein angiography is an essential imaging modality for evaluating eyes with chorioretinal disease and structural complications caused by posterior uveitis. After intravenous injection of fluorescein sodium, a series of filtered posterior segment images provides a functional and structural view of retinal (and to some degree choroidal) vasculature and anatomy. Fluorescein angiography can detect macular edema (Fig 5-11), retinal vasculitis, secondary choroidal or retinal neovascularization, and areas of optic nerve, retinal, and choroidal inflammation. Several of the retinochoroidopathies, or white dot syndromes, have characteristic appearances on FA. Wide and ultra-wide-field FA can identify retinal vascular pathology not noted on clinical examination.
Figure 5-11 Late transit phase fluorescein angiogram of the left eye of a patient with sarcoid-associated anterior uveitis showing a petalloid pattern typical of uveitic macular edema.
(Courtesy of Ramana S. Moorthy, MD.)
Used alone or in conjunction with other imaging, color photographs of the anterior or posterior segment document lesion size, color, location, and morphologic characteristics used to assess clinical progression or regression of disease. These images can be useful in establishing a baseline when assessing a relapsing and remitting inflammatory process (eg, the presence of new posterior synechiae in anterior uveitis, or capturing transitory posterior segment inflammation characteristic of Behçet disease).
Fundus autofluorescence (FAF) imaging is another noninvasive imaging technique for analyzing the posterior segment. It maps the fluorescent property of lipofuscin, a breakdown product of retinal proteins, within the retinal pigment epithelium (RPE). Hyperautofluorescence corresponds to increased metabolic activity of the RPE, or window defect due to loss of photoreceptors. Hypoautofluorescence occurs with loss or blockage of RPE cells. Imaging is useful in posterior uveitis that involves the outer retina, RPE, and inner choroid. Autofluorescence patterns vary between the different uveitides, but in many cases, hyperautofluorescence occurs with increased disease activity and fades and darkens as the inflammation subsides.
Indocyanine green angiography
Like FA, indocyanine green (ICG) imaging uses an intravenous injection coupled with serial retinal images to provide data about vasculature and anatomy of the posterior segment; the properties of ICG allow for specialized imaging of the choroidal circulation. In inflammatory diseases involving the outer retina and choroid, findings on ICG often exceed those visible on either fundoscopy or FA, which can have diagnostic and therapeutic implications. Its use is especially beneficial in the evaluation of inflammatory chorioretinopathies of unknown etiology (white dot syndromes), Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and posterior segment sarcoidosis, and in evaluation of choroidal neovascular membrane (see Chapter 9).
Anterior segment ultrasound biomicroscopy can be useful in diagnosing pathology of the ciliary body, iris, and iridocorneal angle in uveitis. Posterior segment ultrasound, or B-scan ultrasound, can be useful in demonstrating vitreous opacities, choroidal thickening or elevation, retinal detachment, and cyclitic membrane formation, as well as in ruling out occult foreign bodies, particularly if media opacities preclude a view of the posterior segment. Retained IOL fragments may be visualized in the anterior or posterior segment. Ultrasonographic imaging may be diagnostic for posterior scleritis (see Chapter 7).
Full-field electroretinography (ERG) can be used to monitor progression of birdshot chorioretinopathy, diagnose acute zonal occult outer retinopathy (AZOOR) complex diseases, and diagnose autoimmune retinopathy. Electroretinogram findings may also be useful in the uveitis workup when trying to distinguish certain retinal dystrophies from posterior uveitis.
Visual field testing/perimetry
Kinetic and nonkinetic perimetry are used to monitor progression and response to treatment of birdshot chorioretinopathy and AZOOR complex diseases. These techniques are also used to monitor visual field defects in uveitic glaucoma or inflammatory optic neuritis. Microperimetry may be helpful in diseases involving the macula, such as punctate inner choroiditis.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.