Uveitis presents particular problems for ophthalmologists. Inflammation inside the eye can occur from so many causes that the diagnosis often requires painstaking, time-consuming investigation. As researchers have learned more about the disease in recent years, the possible etiologies and treatments have multiplied.
In advising colleagues on uveitis, top experts emphasize patience.
“Why do doctors go into ophthalmology?” asked Stephen Foster, MD. “Mostly, it’s because they are running away from internal medicine. They like intellectual matters and manual dexterity matters and, hence microsurgery. They are very gratified by quick results. Doing the detective hunt required by uveitis with the delayed gratification satisfies very few.”
Dr. Foster is a clinical professor at Harvard University, Boston, and the author of more than 1,000 articles on uveitis. He and Justine Smith, FRANZCO, PhD, a strategic professor at Flinders University, Adelaide, Australia, and president the American Uveitis Society, offered the following clinical pearls for uveitis management.
Systematically, learn everything relevant about the patient–from head-to-toe. Since many uveitis cases stem from systemic conditions, key signs and symptoms can appear far from the eyes.
“There is no slick, quick way of getting to the finish line,” said Dr. Foster. “It takes time and thoughtfulness and meticulousness going about the work of getting to the final diagnosis.”
Bear in mind that certain medications can cause uveitis, including rifabutin, cidofovir, and bisphosphonates, as well as the newer drug, ipilimumab, a monoclonal antibody approved by the FDA to treat malignant melanoma.
The examination must also be comprehensive. This includes techniques such as retroillumination of the iris, which is performed by shining the beam from a slit lamp perpendicularly through the pupil while examining the iris.
The technique can reveal thin areas in the iris indicative of damage from herpes. Only after a thorough history and examination should the clinician decide what tests to order, since it’s not rational to test for every pathogen.
Some types of uveitis thought to be immune-mediated have turned out to originate from infections. This includes many cases of Fuchs heterochromic iridocyclitis, which can be caused by the Rubella virus.
In addition to the “great masqueraders”–syphilis and tuberculosis–Ebola, Dengue Fever, Zika, Chikungunya, and West Nile viruses can also inflame tissues inside the eye. As many as 20% of patients who survive Ebola virus disease go on to develop uveitis from the virus. About 10% of patients hospitalized with Dengue Fever develop uveitis.
“If the reason for uveitis is an infection and you suppress the immune system, you can expect it will get worse,” said Dr. Smith. “If it gets worse, that can be irreversibly damaging for vision.”
For anterior uveitis, clinicians should include syphilis IgG, tuberculosis skin test, or Quantiferon. If the patient has spent time in an area where Lyme disease is present, Lyme Ab should be conducted. If the clinical presentation suggests an infectious cause, polymerase chain reaction assays of aqueous or vitreous fluids can quickly identify many pathogens. For intermediate uveitis, consider an MRI if the patient has neurologic findings.
To treat some infections, clinicians can administer antimicrobials directly into the eye. This can include antiviral agents and clindomycin for some cases of toxoplasmosis.
It is important to test for infections before clinicians start treating patients. Once treatment begins, it can become difficult to detect the pathogens.
Unless the uveitis is caused by an untreated infection, corticosteroids are the best first- line treatment. “After all, the steroids are the only things that can snuff out a fire quickly,” said Dr. Foster.
Clinicians have long relied on prednisolone acetate eye drops, but a newer corticosteroid, difluprednate, offers some advantages. First, it is more potent. Second, it doesn’t require shaking.
Typically, patients don’t shake their prednisolone bottles sufficiently to achieve the necessary 1% concentration–it takes about 30 shakes. Oral corticosteroids can cause side effects, so clinicians should taper them off after bringing down the inflammation. If necessary, turn to other immunomodulatory therapies that are safe for long-term use.
Rimexalone, a lower potency topical corticosteroid than prednisolone, may provide the anti-inflammatory effect needed in the short term. It also reduces the risk of a steroid-induced increase in intraocular pressure (IOP).
If the use of corticosteroids does result in elevated IOP, clinicians can respond with pressure-lowering drops. They should reserve prostaglandin analogs for a last resort because they may worsen inflammation.
Many new immunomodulatory therapies have become available, and sometimes they can put previously recalcitrant cases of uveitis into remission. While older immunomodulatory drugs, such as methotrexate, remain a good next step after corticosteroids, the new biologics offer a potent backup.
These new biologics include adalimumab, which the FDA recently approved for use in uveitis. Most ophthalmologists benefit from teaming up with immunologists, hematologists, or rheumatologists to use these newer medications.
“Many of us have good working relationships with an internist who holds our hand,” added Dr. Smith.