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When treating uveitis with steroids, safety profile must be weighed against efficacy
Route of steroid delivery influences safety and outcomes.
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Local therapy that minimizes toxicity and targets inflammation where it resides is the goal of treating uveitis, according to a retina specialist.
“Steroids remain the first line of therapy for most uveitides,” Szilárd Kiss, MD, told Ocular Surgery News. “Steroids also remain the first line for exacerbations in patients with chronic inflammatory disease that may have an acute flare.”
Although uveitis is a single term, it probably encompasses 25 to 30 diseases, according to Kiss, director of clinical research and an associate professor of ophthalmology at Weill Cornell Medical College.
Szilárd Kiss
“When treating these diseases, at least initially, you first need to differentiate whether the ocular inflammation is infectious or noninfectious,” he said.
Selecting a steroid
Kiss said infectious uveitis should never be treated with steroids, at least not initially. When the infection is believed to be sufficiently controlled with the appropriate anti-infectives, such as antibiotics, antivirals, antifungals or antiparasitics, steroids may then be utilized to control the residual ocular inflammation.
“Hence, you want to rule out the common infections that can cause inflammation in the eye,” he said.
Noninfectious uveitis requires differentiation between an acute condition, acute/chronic condition and chronic condition. The physician also needs to determine whether the disease is associated with systemic illness. For cases that are linked to systemic illness, the severity pattern between the systemic and ocular disease may or may not parallel each other, Kiss said.
The three local routes of administering steroids are topical drops, sub-Tenon’s injections and intravitreal injections, including steroid implants.
“Once the decision has been made to use steroids, the specific route depends on the location of the uveitis,” Kiss said.
For example, acute or recurrent anterior uveitis is typically treated with and responds well to topical steroids. But for posterior uveitis, such as pars planitis or vitritis, or even noninfectious retinitis, a sub-Tenon’s injection or intravitreal route is usually warranted. In addition, posterior uveitis can be treated for a prolonged time with an intravitreal implant such as Ozurdex (dexamethasone intravitreal implant 0.7 mg, Allergan).
Balancing safety and efficacy is key to selecting a particular route of steroids.
“By going inside the eye, you are more likely to have a rise in intraocular pressure and more likely to exacerbate a cataract,” Kiss said.
A steroid drop such as Lotemax (loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb) has a more favorable side effect profile, but the potency is not as great as Durezol (difluprednate ophthalmic emulsion 0.05%, Alcon), he said.
Durezol “is a phenomenal steroid as a topical administration, but it has a vastly different side effect profile than Lotemax, in that many more patients experience an increase in IOP,” Kiss said.
“The type of steroid you use and the frequency of administration will determine your efficacy/potency and side effect profile,” he said.
Intravitreal implants
Of the intravitreal implants, Kiss believes Retisert (fluocinolone acetonide intravitreal implant 0.59 mg, Bausch + Lomb) has the most side effects.
“Retisert is reserved for chronic uveitides that require long-term suppression of the inflammation, typically confined to the eye,” he said. One classic indication for Retisert is birdshot chorioretinopathy.
“The implant causes cataract in 100% of patients,” Kiss said. It can prompt glaucoma surgery, most likely a tube, in nearly 40% of cases, according to Bausch + Lomb.
The dexamethasone implant has an efficacy of 4 to 6 months but may not be sufficient for long-term control of diseases such as birdshot chorioretinopathy.
“Ozurdex has a much more favorable side effect profile,” Kiss said.
In phase 3 trials of the dexamethasone implant, not only did patient symptoms improve for vision and inflammation, but use of adjunctive therapy, either local or systemic, was reduced.
Overall, steroid drops have the lowest risk of causing cataract formation.
“You can probably use Lotemax once a day for a couple of years without any change in lens opacity,” Kiss said.
A sub-Tenon’s injection is more risky for possible cataract formation, while an intravitreal injection or placement of an intravitreal implant poses the highest risk. Over the long term, many patients will develop cataract, but over the medium and short term, the cataract risk is much less with the dexamethasone implant than with a fluocinolone acetonide implant, Kiss said.
To decrease the likelihood of side effects when treating uveitis, Kiss recommended using steroids as sparingly as possible but enough to control intraocular inflammation. – by Bob Kronemyer
Disclosure: Kiss is a paid consultant to Genentech, Regeneron Pharmaceuticals, Alimera and Allergan.