In 2021, Ocular Therapeutix Inc. further expanded the indications for dexamethasone ophthalmic insert 0.4 mg ( Dextenza) upon its FDA approval to treat ocular itching associated with allergic conjunctivitis (AC). It is the first such physician-administered intracanalicular insert that delivers a preservative-free drug, lasting up to 30 days.1
The intracanalicular insert was originally approved in 2018 for the treatment of ocular pain after ophthalmic surgery. In 2019, the drug-delivery platform received an added indication for postoperative ocular inflammation. It is currently undergoing clinical studies for the short-term treatment of the signs and symptoms of dry eye disease.
The current approval for ocular itching associated with AC was based on the results of three randomized, multicenter, vehicle-controlled studies that included 255 patients with a positive history of ocular allergies and positive skin test reaction to perennial and seasonal allergens.2 The dexamethasone insert was associated with lower mean ocular itching scores versus vehicle at all time points throughout the study duration of up to 30 days.
In terms of safety, just 3.2% of patients experienced a transient elevation of IOP which was not in any way severe and quickly resolved when the insert was either flushed out or allowed to finish its course of treatment.2
INTRACANALICULAR INSERT WITHOUT DEXAMETHASONE
In the years since the introduction of punctal plugs, eye care practitioners have been concerned that their use could trap allergens in the ocular adnexa and on the ocular surface. The question was, if allergens were not allowed to dilute with the tear film and be cleared promptly, could patients experience prolonged or worsening disease symptomatology?
A study that explored this question found that not only does punctal occlusion using a polyethylene glycol hydrogel insert with no active ingredient not worsen or prolong symptoms, but on its own was associated with a decrease in hyperemia and patient-reported subjective itching.3 This post-hoc pooled analysis included data from 128 subjects who received the placebo-vehicle insert as part of the three randomized masked clinical trials of dexamethasone ophthalmic insert 0.4 mg using a modified repeat Conjunctival Allergen Challenge Model (Ora-CAC). The insert hydrates and swells to fit the canaliculus, occluding the punctum. The medication is released over 30 days with the hydrogel dissolving and flushing through the lacrimal system.
Ocular itch scores decreased over a 1-month period following punctal occlusion: on days 7, 14 and 28, ocular itching scores were statistically significantly reduced from baseline (P <.05). Following punctal occlusion, post-CAC conjunctival redness scores decreased from baseline for 1 month. On days 7, 14 and 28, conjunctival redness scores were statistically significantly reduced from baseline (P < .05).
EXPERIENCE WITH INSERT, PRACTICAL PERSPECTIVE
The dexamethasone-eluting insert gives us a very powerful treatment option that can be used either as a stand-alone method of treatment or in conjunction with a non-steroidal topical medication if the patient’s symptoms are more moderate to severe. As one of the principal investigators, I was masked to who had placebo versus the investigational product, but it was clear that some patients were having a tremendous response. The data bore this out with statistical significance; treated patients demonstrated decreased subjective symptoms of AC and decreased conjunctival hyperemia. It works, it is straightforward to insert, and it does not require the physician to make any adjustments to their practice flow and scheduling.
Using the dexamethasone-containing insert for AC treatment will be similar to our use of punctal plugs in dry eye patients, with the puncta is dilated and the moisture dried. The user must stretch the lid, pulling it temporally to straighten out the puncta and canaliculus to allow the insert to slide in easily. Similar to diagnosing a patient with dry eye and inserting a punctal plug at that time, there is no reason to have patients return for a separate appointment. We can keep an inventory of dexamethasone ophthalmic insert 0.4 mg on hand and place it when the patient is in the chair and symptomatic. I have been gratified by how quickly patients improve once the insert is in place, as evidenced by not only the slit-lamp examination but more importantly, how much better they feel.
TOXICITY RISKS, COMPLIANCE ISSUES ASSOCIATED WITH DROPS
A major benefit of the intracanicular insert is that it does not require patient compliance and avoids the overuse of medication as can happen in patients symptomatic with allergic conjunctivitis. This timed and titrated dose of dexamethasone is a real game-changer for our treatment regimens, removing concerns around misuse as well as the worry of the potential for significant or prolonged elevated IOP.
We know from our use of dexamethasone ophthalmic insert 0.4 mg to alleviate postoperative pain and inflammation that patients are very happy to have one less medication to remember. Decreasing the burden of eye drops increases adherence and decreases the potential risk of medicamentosa and epithelial surface toxicity from multiple exposures to preservatives. Patients like the convenience and doctors appreciate the safety, consistency, and efficacy of the product for surgical indications as well as allergic conjunctivitis. This really is another advance in our efforts to get away from topical eye drops.
One of the most powerful statements about the efficacy and benefit of this product is the fact that the FDA has given it three on-label different indications for treatment in various sites of care, which should be very reassuring to both doctors and patients with regard to its safety, efficacy, and ease of use.
1. Ocular Therapeutix announces FDA approval of supplemental New Drug Application (sNDA) for DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg for intracanalicular use for the treatment of ocular itching associated with allergic conjunctivitis. October 11,2021. https://tinyurl.com/yfkp48je. Accessed May 16, 2022.
2. Rubin JM, Silverstein SM, Kenyon KR, et al. Pooled analysis evaluating efficacy and safety of an intracanalicular dexamethasone insert for the treatment of allergic conjunctivitis. Paper presented at: ASCRS Annual Meeting; July 23-27, 2021; Las Vegas.
3. Silverstein SM, Sato MA, Meier EJ, et al. Effects of punctal occlusion on ocular itching and conjunctival redness in subjects with allergic conjunctivitis. Paper presented at: SCRS Annual Meeting; April 22-26, 2022; Washington, DC.
Steven M. Silverstein, MD, FACS
Silverstein is the president of Silverstein Eye Centers in Kansas City, Missouri and assistant clinical professor of ophthalmology at the University of Missouri School of Medicine in Kansas City. He is a researcher, lecturer, and advisor for Ocular Therapeutix.