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Need for topical steroids depends on risk factors regimen
About 35% of the general population is susceptible to a significant increase in IOP when given topical steroids.
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Topical steroids can be helpful or harmful, depending on individual risk factors and the type, amount and duration of agent being used, a clinician said.
“Steroids can be our friend, and they can be our foe,” Ronald L. Fellman, MD, said during Glaucoma Subspecialty Day preceding the American Society of Cataract and Refractive Surgery meeting in San Diego. “The problem is that the doctor has to balance the friend with the foe.”
Ronald L. Fellman
While topical corticosteroids reduce inflammation after various types of ocular surgery and treat ocular surface disease, they can also increase IOP and cause cataracts, keratitis and systemic side effects in susceptible patients, Fellman said.
“We as ophthalmologists use steroids after many of our surgeries to suppress inflammation. That’s the mainstay. It suppresses scarring. That’s very important with trabeculectomy surgery,” Fellman said. “But along the same pathway, those steroid drops can cause a high pressure. And they also, as you know, can cause cataract. We also know that when you give somebody a steroid drop, that steroid can get in their bloodstream and cause other side effects.”
Steroid receptors and outflow
Fellman discussed the role of glucocorticoid receptors in governing cellular responses to steroids.
“When you give a steroid into the body or a steroid drop into the eye, up to 6,000 genes are either expressed or suppressed within hours of that drop,” Fellman said. “For example, in the eye, a trabecular meshwork cell is going to respond differently to a steroid than a corneal cell.”
Fellman cited a study by Clark that showed that alpha and beta glucocorticoid steroid receptors in the nuclei of human cells respond to corticosteroids.
Overexpression of glucocorticoid steroid receptor alpha in the trabecular meshwork cells of glaucoma patients causes excess accumulation of extracellular matrix that clogs the drainage system, Fellman said.
Conversely, trabecular meshwork cells in glaucoma patients lack the expression of glucocorticoid receptor beta.
“The beta isn’t there to inhibit the alpha, so the alpha clogs up the system and the pressure goes up,” he said.
Managing, mitigating risk
About 35% of the general population experiences a significant rise in IOP with the use of topical steroids, Fellman said.
“In the entire population, 5% of people will have a big-time pressure response to steroids. More like 30% will have a moderate increase. So, that’s kind of what we worry about,” Fellman said.
Fellman cited a study by Armaly that showed that among patients who received one drop of dexamethasone phosphate three times daily for 4 weeks in one eye, IOP increased 5 mm Hg or less in 66% of patients, 6 mm Hg to 15 mm Hg in 29% and 15 mm Hg or more in 5%.
In addition, topical steroids can raise IOP in the untreated eye because of systemic absorption, Fellman said.
“When you put an eye drop in, it gets in your body. It gets absorbed. We know that with all of the side effects of all of our glaucoma drops,” he said. “And it turns out that the people who are most likely to have that pressure elevation in the fellow eye are the people who are what we call steroid responders. They’re the high-level responders.”
Eyelid closure is recommended to prevent systemic absorption in susceptible patients, Fellman said.
About 90% of patients with primary open-angle glaucoma are at risk for IOP increases with steroids, Fellman said. He noted that other risk factors include low-tension glaucoma, first-degree kinship with a POAG patient, more than 5 D of myopia, type 1 diabetes, previous steroid use, traumatic glaucoma, and penetrating keratoplasty for Fuchs’ dystrophy or keratoconus.
“If you do have a patient who is a high responder, you have to either reduce the potency of the steroid or you decrease the frequency of it. Or maybe you switch over to a nonsteroidal anti-inflammatory agent,” Fellman said.
For patients who are initially started on intravitreal, periocular or oral steroids, Fellman recommended checking IOP every 2 weeks in the first month, monthly for 2 or 3 months, and then every 3 to 6 months to determine their steroid response and assess their risk factors.
Microincisional glaucoma surgery does not protect a patient from a steroid-induced IOP increase, Fellman said. He cited a mouse model study by Overby and colleagues that showed that fibroblasts, when exposed to a steroid, turned into myofibroblasts that generated extracellular matrix and clogged downstream collectors.
“You still have to worry about the effects of the steroid on the downstream collector channels,” he said.
Steroids are beneficial in filtration surgery such as trabeculectomy, he said. – by Matt Hasson
For more information:
Ronald L. Fellman, MD, can be reached at Glaucoma Associates of Texas, 10740 N. Central Expressway, Suite 300, Dallas, TX 75231; email: rfellman@glaucomaassociates.com.Disclosure: Fellman reports no relevant financial disclosures.