Study demonstrates power of IRIS Registry for evaluation of safety, efficacy
Although novel ophthalmic medications and delivery systems continue to emerge, many surgeons are hesitant to use them in patients until comprehensive evidence accrues to support their application.
For some individuals, data from clinical trials simply aren’t enough. Many of us have had the frustrating experience of treating patients with a new therapy only to observe an incidence or severity of adverse events that don’t match the safety profile recorded in trials.
I’m an avid believer in the power of findings from real-world studies to demonstrate what we can expect from a drug. Unlike trials, which often include patients who are free of comorbidities, real-world studies reflect the populations we encounter in the clinic. As the senior medical director at Verana Health, a digital health company elevating quality in real-world data, I spearhead such studies using deidentified electronic health record data from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry.
Using our clinician-informed and artificial intelligence–enhanced VeraQ population health data engine, the Verana Health team curated deidentified data from the IRIS Registry to investigate the real-world performance of an intracanalicular dexamethasone insert designed to manage postoperative inflammation and pain and ocular itching associated with allergic conjunctivitis. Our study, the largest ever to evaluate Dextenza (dexamethasone ophthalmic insert), was intended to determine whether the 0.4-mg, resorbable, preservative-free insert would reflect the safety data on its label1 in patients recovering from cataract surgery.
Delivery of Dextenza to the ocular surface via the punctum, where it provides sustained-release treatment for up to 30 days, seems like a clear way to ensure adherence with a corticosteroid course after cataract surgery. The insert spares patients from repeated corticosteroid eye dropper use, which is helpful for those with dexterity issues or other barriers to adherence. Our team suspected many surgeons would be reluctant to use a newer corticosteroid delivery system without data demonstrating how it might affect IOP, especially in patients with glaucoma or ocular hypertension.
Our findings, which we presented at the American Society of Cataract and Refractive Surgery Annual Meeting in April 2022 in Washington, DC, help resolve that question by demonstrating that the real-world safety and efficacy profile of Dextenza following cataract surgery is consistent with the information on the product’s label for the management of inflammation and pain following ophthalmic surgery. These are the kinds of findings that help fuel advancement in eye care, and they couldn’t have been generated without a postmarket study or without curated data from the IRIS Registry, which captures the treatment histories of 79 million unique deidentified patients.
Our safety study included patients who underwent cataract surgery between June 1, 2019, and March 31, 2021. Researchers evaluated 10,313 eyes that received treatment with Dextenza and 425,098 eyes that received standard care—likely consisting of topical corticosteroid drops—before or after surgery. Patients from both cohorts were selected from practices that offered Dextenza as a treatment option.
The study evaluated the incidence of inflammation events such as uveitis, corneal edema, cystoid macular edema, endophthalmitis, epiphora, and lacrimal disorders. An additional safety measure assessed IOP elevations and changes from baseline.
We found that the overall incidence of inflammation events after surgery was low and comparable between the group that received Dextenza and the group that did not. When comparing the real-world Dextenza group with cohorts that received the insert in clinical trials,2,3 a key result stood out: The patients in our real-world study had a lower rate of anterior uveitis than their clinical trial counterparts: 1.16% vs 9.87%, respectively. Corneal edema was also less common in the real-world study, with a rate of 0.5% vs 1.4% in clinical trials.
The study also measured rates of postoperative IOP elevation reaching 10 mm Hg or more. Patients with no history of glaucoma were somewhat more likely to reach those elevations in the real-world study than in clinical trials (7.5% vs 6.5% on the day after surgery). However, when comparing the 2 arms of our real-world study, patients in the non-Dextenza cohort were more likely to reach IOP levels of 10 mm Hg or more, with a rate of 8.7% the day after surgery. Notably, in patients with glaucoma, IOP levels in that range were comparable across the Dextenza and non-Dextenza real-world cohorts.
In a separate look at the characteristics of study participants who received Dextenza in our real-world study, we reported some early trends in the way ophthalmologists selected patients to receive the insert after cataract surgery. Across the 2 real-world cohorts, Dextenza and standard treatment were used comparably, regardless of cataract or surgery type.
But we found that patients with preexisting dry eye disease or other ocular surface conditions were more likely to receive Dextenza than standard treatment for inflammation. In the study group, 32.1% of patients with dry eye received Dextenza, whereas in the control group, 24.5% of patients with dry eye received standard treatment for inflammation. This could indicate that surgeons selected patients with dry eye to receive Dextenza, perhaps to avoid the adverse effects of topical corticosteroids, some of which include preservatives.
Another important finding was that Dextenza was used in patients with glaucoma. Overall, the study showed that Dextenza was administered slightly less frequently than standard care in patients who had undergone glaucoma procedures in the 6 months prior to cataract surgery (0.8% vs 1.4%). However, 8.6% of study participants who received the insert underwent a glaucoma surgery the same day as cataract surgery. This suggests that early adopters of Dextenza are confident in its safety after cataract surgery, even for patients with glaucoma. It’s a noteworthy finding because ophthalmologists tend to be cautious about trying novel treatments in general4 and specifically in these patients because of concerns about their IOP stability.
Going forward, the use of Dextenza in patients with glaucoma deserves more study. It could be worthwhile to investigate how the insert stacks up after specific glaucoma procedures, from minimally invasive surgery to trabeculectomy.
The IRIS Registry will remain an outstanding resource for data when researchers are ready to tackle these investigations. In fact, the IRIS Registry’s database will be enriched as Dextenza spends more years on the market and is used in more eyes, generating new and helpful information that can be harnessed for future studies.