Pearls for recognizing and treating uveitis

Reviewed by Thomas A. Albini, MD.

Uveitis specialists are in short supply in the United States, with only approximately 8 programs available nationally, making the disease difficult to diagnose in some cases. Thomas Albini, MD, a professor of clinical ophthalmology at the Bascom Palmer Eye Institute in Miami, Florida, described 2 difficult cases and provided his pearls for using the latest diagnostic and treatment advances.

Case 1

A 62-year-old man was referred with a history of posterior segment noninfectious uveitis in the left eye (OS), which was previously treated with dexamethasone intravitreal implant (Ozurdex; Allergan). After receiving 2 injections (possibly steroids), he returned with worsening of vision and cystoid macular edema (CME). Treatment with a 2-week course of prednisone (60 mg) daily resulted in visual improvement.

Optical coherence tomography images showed hazy media and CME OS, and fluorescein angiography (FA) showed diffuse vascular leakage bilaterally. A scar was present OS, suggesting toxoplasmosis, which required serologic evaluation. Eliminating that diagnosis is important because steroid use can exacerbate uveitis. He also underscored the importance of performing FA, which can visualize overlooked pathologies.

Treatment included prednisone tapering to 40 mg daily and reevaluation in 1 to 2 weeks, with prednisone tapering over 2 months. Adding a 2-year course of methotrexate was a potential consideration, but with disease recurrence, immunomodulation was needed for an extended period.

Bilateral undifferentiated intermediate uveitis was diagnosed. Albini advised obtaining broad imaging to spot any pathologies that otherwise may go unnoticed and identifying neurologic symptoms that might help to fine-tune the treatment strategy. Tuberculosis, sarcoidosis, and syphilis should be ruled out. “The most important thing is to rule out infectious causes,” Albini said.

He advised questioning patients about potential risk factors for uveitis, such as smoking. CME is more likely to develop in patients who smoke. “With this patient, a treatment that lasts over the long term is needed for chronic inflammation,” he said. However, high-dose steroids are inappropriate over the long term. Steroid-sparing drugs, such as methotrexate dosed weekly and mycophenolate mofetil (CellCept; Roche)dosed twice daily, are the mainstays of uveitis treatment. Adalimumab (Humira; AbbVie) also is available for posterior uveitis but at tremendous cost. Another option is the local steroid implants, fluocinolone acetonide intravitreal implant (Retisert; Bausch + Lomb).

Albini thinks suprachoroidal drug delivery rather than steroids will be more impactful for the choroid/retina and less so on the trabecular meshwork/lens. Some data from gene therapy treatment of diabetic macular edema showed good benefit with drugs delivered suprachoroidally.

The patient is currently taking 20 mg of subcutaneous methotrexate and feels well, with no medical issues. The prednisolone was tapered to 5 mg. He undergoes periodic laboratory evaluation. However, he has had recurring inflammation and CME with methotrexate, at which point the long-acting fluocinolone implant was added. Over the course of 1.5 years of treatment, his vision has improved from 20/60 to 20/40.

“The current standard of care is to rule out infectious cases, treat with steroids acutely, and treat carefully. If uveitis recurs and patients need more than 7.5 mg of steroids chronically, use steroid-sparing agents,” Albini said. Importantly, patients also must be informed about the recurrent nature of their disease.

Case 2

A second case was that of a 54-year-old man with episodic blurry vision bilaterally over the course of the previous few months. The episodic severity varied and last up to 5 minutes. His most recent episode occurred 1 week before evaluation and lasted for 10 minutes. The patient reported photophobia that was more intense OS. He had a history of hypertension, prostate cancer, chronic anxiety, and fibromyalgia.

The patient was taking oral prednisone, as well as treatments for anxiety, pain, blood-pressure lowering, and gastrointestinal issues. The visual acuities were 20/40 and 20/20. There were no cells in the anterior chamber. Imaging showed radially oriented lesions around the optic disc.

Indocyanine green angiography (ICG) revealed a pattern of uniformly distributed small hypo-fluorescent spots that establish the diagnosis of birdshot chorioretinopathy bilaterally. A pearl in such patients is that robust anterior chamber inflammation is not a sign of birdshot. In cases that appear to be unilateral birdshot, Albini considers sarcoidosis.

Another pearl is that the inferonasal quadrant generally has the highest number of spots in patients with birdshot. “The recognition is growing that birdshot can be present without these lesions, making diagnosis harder. However, ICG findings in the mid to late stages are diagnostic,” he said.

Most patients are HLA-A29 positive. Other things that point to birdshot are bilateral CME, which is a common finding, and older patients with vitritis, symmetric disease, and always bilateral findings. FA shows first-order retinal vasculitis, with symmetric and bilateral leakage from veins at the disc. These findings can help identify birdshot in patients without spots (approximately 10% of cases). The patient under discussion also had small epiretinal membranes, which are associated with vision loss.

Treatments included mycophenolate mofetil, azathioprine(Thioprine; Mylan Pharmaceuticals), and cyclosporine, which were not well tolerated. He received fluocinolone acetonide bilaterally and the vision and visual fields improved. A finding that remains with fluocinolone acetonide is engorged choroids, suggesting possible inadequate treatment. However, Albini believes the treatment is reasonable based on patient outcomes. He tends to treat patients with mild disease with steroids and immunosuppression therapy.

In the current case, the vision continued to improve with fluocinolone acetonide. After the second treatment, the vision was 20/25 with stable visual fields. With later development of CME, he received a dexamethasone injection and endophthalmitis developed. The vision recovered to 20/200 in the affected eye.

Uveitis is an uncommon disease that is less known than other retinal diseases. Because of that, patients may be reluctant to accept treatment and are afraid of immunomodulation despite its safety.