Three pearls for uveitis diagnosis

Diagnosis in a patient with uveitis can be challenging because the uveitides represent a large group of intraocular inflammatory diseases, but establishing the etiology is important to guide appropriate therapy.

Discussing uveitis diagnosis at the Retina Subspecialty Day meeting, Narsing Rao, MD, stressed the importance of not missing infectious causes or an associated systemic disease and the need to obtain ocular fluid or even a tissue sample when uveitis remains unexplained and the disease is progressing with vision loss.

“Although it is a challenge in knowing the cause of uveitis in many patients presenting with intraocular inflammation, very attempt should be made in arriving at etiologic diagnosis of uveitis and related intraocular inflammation,” said Dr. Rao, professor and chairman of ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles.

Identifying an infectious cause of uveitis is important because such cases can be effectively resolved with pathogen-specific antimicrobial therapy and may be worsened if treated empirically with immunosuppressive agents.

Toxoplasmosis, syphilis, tuberculosis (TB), and acute retinal necrosis caused by viruses, particularly herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV), are the important causes of infectious uveitis.

When one of these causes is suspected based on the history and clinical findings, appropriate laboratory testing can be done to confirm the diagnostic impression, Dr. Rao said.

Serological testing for toxoplasmosis measures IgG and IgM antibodies. Testing for syphilis can be done using the rapid plasmin reagin or venereal disease research laboratory tests and fluorescent treponemal antibody absorption.

“Any patient who has a positive test result for syphilis should also be tested for HIV infection because syphilis and HIV often coexist,” Dr. Rao said.

Testing for TB can be done with the purified protein derivative skin test, but the interferon-gamma release assay is more specific. In addition, chest imaging with x-ray or a high definition computed tomography scan is indicated because TB usually begins in the lungs. If HSV, VZV, or CMV is suspected, a blood sample can be submitted for measurement of antibodies or ocular fluid may be submitted for polymerase chain reaction (PCR) analysis to detect viral DNA.

Proper diagnosis of patients with uveitis also requires not overlooking the possibility that the intraocular inflammation is a manifestation of an underlying systemic disease.

“It is important to diagnose an associated systemic condition because in addition to local ocular treatment to control the intraocular inflammation, early therapeutic intervention for the systemic disease can prevent its related morbidity and even mortality,” said Dr. Rao.

The systemic diseases that are associated with uveitis include infectious and non-infectious conditions.

In addition to TB, syphilis, and toxoplasmosis, systemic infectious diseases that may be associated with uveitis include Lyme disease, cat-scratch disease, and Whipple disease.

Uveitis can also be a manifestation in patients with inflammation of the central nervous system. In particular, multiple sclerosis might be considered in the differential diagnosis for a patient with intermediate uveitis, and the investigation for multiple sclerosis can begin by asking patients about the presence of neurological symptoms, Dr. Rao said.

Uveitis can also be associated with vasculitides, particularly Behçet’s disease, granulomatosis with polyangiitis and with systemic inflammatory diseases, including Vogt-Koyanagi-Harada disease and sarcoidosis.

In addition, findings that appear to be signs of intraocular inflammation may be related instead to a masquerading hematologic neoplastic disease.

If the diagnosis remains uncertain because findings of a directed work-up were negative and the inflammation and vision are worsening, clinicians should consider obtaining a vitreous fluid sample or even a tissue biopsy for cytopathology diagnosis. Direct communication with the pathologist is necessary in these situations so that the samples will be processed appropriately, Dr. Rao said.

“Let the pathologist know upfront if based on your clinical impression you are suspecting infection or a malignant cause,” he explained.

Testing of the vitreous for diagnosis of lymphoma should include cytological evaluation for malignant lymphocytes, immunohistochemistry to determine clonality of tumor cells, flow cytometry assessment for multiple surface markers, PCR to determine clonal rearrangements in immunoglobulin genes, and determination of the IL-10/IL-6 ratio.

“The latter test is not an absolute diagnostic indicator of intraocular lymphoma, but it can be helpful for supporting the diagnosis,” Dr. Rao said.