Oral, Topical Carbonic-Anhydrase Inhibitors for Glaucoma Similarly Safe

NEW YORK (Reuters Health) – Whether glaucoma patients take carbonic-anhydrase inhibitors (CAIs) as pills or eye drops, the risk of severe adverse events is low, researchers in Canada report.

There has been some reluctance among ophthalmologists to prescribe oral CAIs, given the potential for life-threatening systemic adverse reactions, they note in JAMA Ophthalmology. The new analysis “supports reconsidering the reluctance,” Dr. Marko M. Popovic of the University of Toronto, Canada, and colleagues write.

“In a large population-based analysis, we found that both oral and topical CAIs had low risk of serious adverse events. There was only a slightly higher risk with oral agents relative to topical therapy,” Dr. Popovic told Reuters Health by email.

“In the absence of contraindications or issues with patient intolerance, oral CAIs can be considered to lower intraocular pressure in patients who have uncontrolled glaucoma despite maximal topical therapy,” he added.

The researchers identified nearly 129,000 consecutive patients over 65 in the province of Ontario, half of whom were prescribed oral and half topical CAIs over a 25-year period. The two groups were matched by age, sex and diabetes status. The mean age overall was 75 years, and 19% had diabetes.

The researchers reviewed the patients’ data for 120 days from the date of their first prescription to find severe complications, including Stevens-Johnson syndrome, toxic epidermal necrolysis and aplastic anemia.

The absolute risk of a severe complicated adverse event in patients prescribed pills was 2.90 per 1,000 patients, while the absolute risk for those prescribed eye drops was 2.08 per 1,000 patients. The difference was equivalent to a risk ratio of 1.40, with a number needed to harm of 1 in 1,220 patients (P=0.003).

Risk was also low in multivariable regression analysis that controlled for confounding factors. Patients with more comorbidities and those with more-frequent clinic visits tended to have more severe complicated adverse events.

Three experts who were not involved in the study told Reuters Health by email that the large scale of the study and the reinforcement of previous knowledge were strengths of the study.

“This large amount of data is great for confirming our prior understanding,” said Dr. Andrew Pouw, a clinical assistant professor of ophthalmology and visual sciences at the University of Iowa Carver College of Medicine in Iowa City.

“A weakness of the study is that it did not look at dosing,” he noted. “That information would have helped us identify thresholds for safe and less safe dosage amounts.”

Dr. Michael M. Lin, a glaucoma specialist at Massachusetts Eye and Ear in Boston, said, “It remains important to weigh the decision to start oral carbonic-anhydrase inhibitors carefully, but I generally feel comfortable prescribing acetazolamide to most of my patients who need additional intraocular pressure control.”

Dr. Lin added that ophthalmologists use CAIs frequently, and that “the study confirms that oral CAIs can be used safely for many patients. It provides more evidence that may help persuade physicians to be less hesitant about prescribing oral CAIs when necessary.”

He added that, although the cohort study design that included a large population is a strength of the study, “this design also raises concerns about the validity and quality of the data entered into the database.”

Dr. Simon K. Law, a glaucoma specialist at the UCLA Stein Eye Institute in Los Angeles, said, “I don’t think clinicians will increase prescribing or using oral CAIs based on the findings of this study. The reluctance toward prescribing oral CAIs is not mainly due to severe complicated adverse reactions as studied in this analysis, but because of the availability of other effective medications with lesser side effects and greater ease of use.”

The study did not receive commercial funding. One author reports financial relationships with drug companies unrelated to the study. The remaining authors and the independent experts declare no potential conflicts of interest.

SOURCE: https://bit.ly/3uvjZfO JAMA Ophthalmology, online January 27, 2022.

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