Uveitis is associated with a wide range of underlying causes. Familiarity with its clinical manifestations, referral indications, and treatment strategies are required for the optimal use of current therapeutic options.
Uveitis can be caused by infectious and non-infectious factors, resulting in differing prognoses and treatments. The treatment of chronic, non-infectious uveitis has profoundly changed in the last years due to the advent of biologicals, but also of intraocular therapies.
For many years, uveitis was considered a single disease entity; therefore, the approach to treatment varied very little.
As knowledge of the disease process grew and the sophistication of immunologic and microbiologic testing increased, the fact that uveitis entails a multitude of diseases became clear.
Although some diseases are local ocular immune phenomena, many of them are systemic diseases with ocular manifestations.
Because the spectrum of disease pathogenesis ranges from autoimmunity to neoplasia to viruses, the practitioner of uveitis requires an understanding of internal medicine, infectious diseases, rheumatology, and immunology.
Patients with uveitis can present with some of the most challenging diagnostic dilemmas in all of ophthalmology.
The recent progress made for patients with uveitis range from better diagnostics to newer formulations of steroids to systemic immunosuppressants, and these are leading to better outcomes, according to Olivia L. Lee, MD, an associate professor of ophthalmology and director of the Anterior Segment Imaging Laboratory at the Gavin Herbert Eye Institute at the University of California, Irvine.
Lee recently discussed the progress that has been made in patients with uveitis from better diagnostics to newer formulations of steroids to systemic immunosuppressants.
Diagnostics Lee detailed a complex case of a 35-year-old woman with unilateral hypertensive iridocyclitis in the left eye. The anterior uveitis was chronic and was associated with very subtle changes in the iris stroma at the pupillary margin.
A posterior subcapsular cataract was present and there is an increased cup-to-disc ratio. Glaucoma drops alone provided suboptimal control of the intraocular pressure (IOP).
Lee performed an anterior chamber tap and obtained a peripheral blood sample; the resultant Goldmann-Witmer coefficient was positive for rubella (19.34), she reported.
This analysis led to the diagnosis of Fuchs heterochromic iridocyclitis associated with rubella. “No treatment is needed for rubella and topical steroids are not helpful. Cycloplegia is unnecessary because synechia do not develop,” Lee said.
“Treatment was focused on IOP control. In this case, the diagnosis was established with a very small sample of aqueous.”
Lee then discussed other testing that can be done with small aqueous samples to address whether uveitis is infectious or noninfectious. In patients with uveitis, polymerase chain reaction (PCR) is superior to cultures, the gold standard, because of its higher sensitivity and the small sample volume needed.
PCR has been used to diagnose many conditions, such as viral anterior uveitis/retinitis, toxoplasma chorioretinitis, ocular tuberculosis, Whipple disease, cytomegalovirus (CMV) endothelitis and anterior uveitis, ocular histoplasmosis syndrome, and endophthalmitis.
All physicians, even those outside large academic institutions, can send ocular specimens for PCR testing. A variety of tests on ocular fluid are available through ARUP Labs, University of Washington, and Casey Eye Institute.
Extensive testing of viruses, mycobacteria, autoimmune retinopathy panels, and cancer- and melanoma-associated panels is available. Ocular imaging advances “Multimodal imaging is the current rage,” Lee pointed out.
Multiple imaging techniques are available to diagnose and evaluate uveitis that includes identifying the location and degree of the inflammation. These capabilities apply to use in the clinic and to an objective and reproducible way for use in clinical trials, she explained.
Optical coherence tomography (OCT) can be used, in addition to all of its other uses, to evaluate cells in the anterior chamber and vitreous cavity. Lee recounted a study performed using the Topcon DRI Titan swept-source (SS) OCT machine to evaluate anterior cells in eyes with uveitis.
The eyes were graded at the slit-lamp using SUN criteria for anterior chamber cell and flare and then compared to images obtained using SS-OCT. Lee reported that in the 4+ anterior chamber cell group, the particulates were easy to visualize.
“However, in the eyes in which I saw no cells clinically, I was surprised to see that the OCT picked up some small cellular material,” she said. Lee found that the correlation between the SUN clinical grading and the presence of cells seen by anterior-segment OCT was very good.
“This technology also can be used to look at vitreous cell and haze,” she said. When considering fundus fluorescein angiography, peripheral vasculitis would have been overlooked if sweeps of the peripheral retina were not done.”
Widefield fundus imaging is important not only in retinal vasculitis but also in a number of other conditions with peripheral pathology, Lee said.
Treatments Corticosteroids have been the go-to therapy for uveitis for 70 years. Currently, new steroid formulations provide a variety of routes of administration and sustained drug-delivery devices. The choice is made based on the desired potency and location of drug delivery.
For example, intravitreal steroids can be injected to treat uveitic cystoid macular edema (CME); however, this method is associated with a limited treatment duration and sets the stage for recurrent disease. The answer to this is use of a sustained-drug delivery devices.
Retisert (fluocinolone; Bausch & Lomb), the first to receive FDA approval, lasts 30 months, requires surgical implantation, and frequently results in cataract and glaucoma development. Ozurdex (dexamethasone; Allergan), injected during an office procedure, is effective for 4 to 6 months.
Yutiq (fluocinolone; EyePoint), approved to treat noninfectious uveitis, has a longer effective treatment duration than Ozurdex, but Lee said she believes Ozurdex is better for treating active disease than Yutiq, which is better for maintenance.
FDA approval of a suprachoroidal steroid implant, Xipere (triamcinolone acetonide; Bausch & Lomb), is in the offing. The device, which is contained in a loading system, is inserted by applying pressure perpendicular to the sclera about 4 to 5 mm posterior to the limbus and delivers 4 mg of drug to the suprachoroidal space.
In the PEACHTREE phase 3 study, the device met its end points with improvements in vision and macular thickness. Safety is always an issue. The SITE Cohort Study3 included about 8000 patients followed for 26 years to evaluate the safety of systemic immunosuppression.
The study found no significant increased risk of death among patients treated for uveitis. The cyclophosphamide-treated group had a significant increase in cancer mortality.
Among the immunomodulatory agents, the biologic response modifiers are the newest drug class developed to treat autoimmune diseases.
These agents are derived from or resemble naturally occurring effector molecules in the inflammatory cascade. Adalimumab (Humira; Abbott Laboratories) was approved to treat noninfectious intermediate posterior and panuveitis in patients aged 2 years and older.
The newest citrate-free formulation is better tolerated by patients.