Rethinking punctal occlusion as an option for allergic conjunctivitis

The intracanalicular dexamethasone ophthalmic insert (Dextenza; Ocular Therapeutix) incorporates 0.4 mg of dexamethasone into the hydrogel matrix to treat postoperative inflammation and pain following ocular surgery. It is also approved for the treatment of ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged 2 and older who do not require sedation for insertion. Additionally, it is free of antimicrobial preservatives. However, some clinicians have hesitated to use punctal occlusion in patients with allergies, out of concern that occluding the puncta could trap allergens on the surface and worsen symptoms of allergic conjunctivitis.

The studies that led to approval of the dexamethasone insert for this indication found it to be effective at reducing ocular symptoms, with a favorable safety profile.^1,2 More recently, a post hoc analysis of only the control groups from these studies—in other words, the eyes that received the placebo inserts—was conducted to determine whether punctal occlusion worsened signs and symptoms in a modified version of the traditional conjunctival allergen challenge (CAC) model.³

Based on the post hoc pooled analysis results, punctal occlusion with an unmedicated resorbable hydrogel intracanalicular insert did not worsen ocular itching or conjunctival redness. Signs and symptoms improved (Table),³ although to a lesser extent than in participants who received the insert containing dexamethasone.³ A placebo response is not unexpected in a placebo-controlled trial. These findings suggest that punctal occlusion itself likely reduces the allergen-antigen reaction rather than exacerbating it.

Study design

In the 3 pooled studies, patients were screened 7 to 45 days before being randomly assigned 1:1 to either the active dexamethasone insert (n = 127 across all 3 studies) or a placebo insert (n = 128). This pooled post hoc analysis incorporated data from 3 randomized, placebo-controlled clinical trials: study 1 (NCT02445326), study 2 (NCT02988882), and study 3 (NCT04050865). The placebo was a polyethylene glycol-based hydrogel insert (the same as the dexamethasone insert) containing no active ingredient. Participants in the studies were healthy adults with a personal history of ocular allergy and a positive skin test reaction to a perennial allergen, such as pet dander or dust mites, or to a seasonal allergen, such as trees or grasses. The insert placement and baseline CAC occurred on day 1, and participants were exposed again on days 6, 7, 8, 13, 14, and 15 (all 3 studies) and on days 26, 27, and 28 (studies 1 and 2 only).

The CAC model is a well-established and rigorous method for evaluating allergy treatments. In these studies, a modified CAC model was used, in which the standard single challenge was expanded to include multiple repeated challenges over several visits. This modified model was challenging for patients because they were deliberately exposed to the allergen multiple times across repeated visits. This repeated allergen exposure induces an acute reaction in the presence of late-phase inflammation, in addition to early-phase inflammation—similar to what an allergic conjunctivitis sufferer would experience in the real world. Success with this model demonstrates that the patient has built up an effective dose that significantly reduces or eliminates their allergic signs and symptoms and maintains its effect throughout the duration of the study and the life span of the insert.

Personal clinical experience

Patients with allergic conjunctivitis typically present with no medications or take a systemic allergy medication—eg, loratadine (Claritin; Bayer), cetirizine (Zyrtec; Kenvue), or pseudoephedrine (Sudafed; Kenvue)—which has the unwanted effect of drying out the ocular surface and worsening discomfort. I encourage patients to taper off these medications unless they have significant rhinorrhea.

When patients present with allergy symptoms accompanied by clinical signs of allergy, I find that in-office treatment with the dexamethasone insert provides immediate therapeutic benefit. The insert remains effective for approximately 1 month, after which it can be replaced if needed. Patients appreciate not having to fill a prescription or administer daily drops.

For individuals with more severe signs and symptoms, a topical antihistamine–mast cell stabilizer may also be prescribed, with the intracanalicular steroid serving as an induction agent while the effect of the topical medication builds, similar to the use of a topical steroid when initiating cyclosporine or other dry eye therapies. In most cases, however, the intracanalicular steroid insert functions effectively as monotherapy for resolving redness and itching.

The dexamethasone insert would not be appropriate for known steroid responders. IOP is checked at pre-insertion and during follow-up, although IOP spikes are very uncommon with this delivery method.

Insertion technique

Insertion is straightforward for any clinician familiar with punctal dilation and has a short learning curve for those who are not. The punctum is gently held downward and temporally to stretch it, and the insert is then slid into place. Once positioned, the insert can be irrigated down the nasolacrimal duct if necessary. However, after several thousand insertions, I have learned that removal is rarely required. This type of insert seldom extrudes or falls out, as it eventually resorbs. Once patients with allergies are identified, they can be scheduled for insert placement the following year in late winter, ahead of their allergy season.

I also recommend that patients with allergies consistently use artificial tears that are free of preservatives to relieve their dry eye symptoms and to help dilute the allergen. Avoidance of known allergens should be emphasized, and I recommend using a refrigerated Bruder mask as a daily cool compress.

With a global prevalence of allergic conjunctivitis of 40% and growing, novel solutions for treating ocular allergies are needed.⁴ Punctal occlusion does not exacerbate symptoms. In my practice, the dexamethasone insert has been an effective tool for controlling allergy symptoms, particularly in the acute phase of the immune reaction, and reducing the burden of systemic medications for patients.

Steven M. Silverstein, MD, FACS

E: [email protected]

Silverstein is an assistant professor of ophthalmology at the University of Missouri-Kansas City School of Medicine and a clinical professor of ophthalmology at Kansas City University College of Biosciences, and he is in private practice at Silverstein Eye Centers in Kansas City, Missouri. He is a researcher and lecturer for Ocular Therapeutix.

References

1. Kenyon K, McLaurin EB, Silverstein SM, et al. A randomized, multicenter phase 3 clinical trial evaluating intracanalicular dexamethasone insert for the treatment of allergic conjunctivitis. Clin Ophthalmol. 2024;18:2671-2684. doi:10.2147/OPTH.S476419

2. McLaurin EB, Evans D, Repke CS, et al. Phase 3 randomized study of efficacy and safety of a dexamethasone intracanalicular insert in patients with allergic conjunctivitis. Am J Ophthalmol. 2021;229:288-300. doi:10.1016/j.ajo.2021.03.017

3. Silverstein SM, Sato MA, Meier EJ, et al. Effects of punctal occlusion on ocular itching and conjunctival redness associated with allergic conjunctivitis. Curr Eye Res. 2023;48(9):781-787. doi:10.1080/02713683.2023.2211247

4. Miyazaki D, Fukagawa K, Okamoto S, et al. Epidemiological aspects of allergic conjunctivitis. Allergol Int. 2020;69(4):487-495. doi:10.1016/j.alit.2020.06.004