Drops vs inserts: Which increases adherence?

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As an optometrist at a practice specializing in contact lenses, I treat many patients who have keratoconus. However, keeping them comfortable can be a struggle, particularly when they have comorbid ocular inflammatory conditions such as allergies and dry eye.

Although several drugs can ease inflammation, patients who wear specialty contact lenses have a fairly high rate of nonadherence with topical medications.

Fortunately, encouraging news came out of a study I presented last year,¹ which found that a time-released steroid placed into the lower punctum and then into the canaliculus may be a good alternative to drops for some of these patients.

Numerous risk factors for nonadherence

Keratoconus is characterized by progressive thinning and steepening of the cornea, leading to decreased visual acuity and irregular corneal astigmatism.² Several comorbid inflammatory ocular conditions may be more evident in patients with keratoconus, including dry eye, allergy, asthma, atopy, and eczema.^3,4

An initial option for reducing ocular inflammation due to allergies is an antihistamine or mast cell stabilizer (or combination) eye drop, but when that does not work, a short dose of topical steroids is a good choice. However, patients with keratoconus can have a difficult time adhering to these regimens because many rely so heavily on their specialty contact lenses—not only to engage in daily activities but also for comfort. As a result, having to remove their lenses to instill drops multiple times a day is a deterrent to adherence. This is particularly true for patients who need assistance from family members both to administer drops and with application of their lenses, as scheduling conflicts can result in skipped doses.

At the other extreme, I sometimes encounter patients who instill their drops too often, either because they are enthusiastic about the relief they are experiencing or because they accidentally use their steroid drops instead of allergy drops or artificial tears.

Patients can also have underwhelming results if they forget to shake the steroid bottle or lose track of their dosing schedules because they are juggling a host of drops prescribed to treat a variety of conditions. As optometrists know, the more drops we add, the harder it is for patients to remember which medications to use in the morning, which to use at midday, and which to use in the evening.

Finally, there are patients like many of those in the community I treat, who cannot afford their eye medications if health insurance refuses to cover them.

A good estimate of the frequency of nonadherence comes from a large study conducted in patients with glaucoma or ocular hypertension, populations also known to struggle with adherence.⁵ In that study, the self-reported rate of nonadherence was approximately 40%.

Considering insertable steroids in a hard-to-treat population

I often see evidence of nonadherence at follow-up visits, when I find persistent clinical signs of inflammation in patients with keratoconus who wear specialty contact lenses. That reinforces the importance of comprehensive education around the use of steroid drops. But it also highlights the need to find new ways to support adherence while improving comfort and ocular signs.

That is why, when I learned about a 0.4 mg resorbable intracanalicular dexamethasone insert (Dextenza; Ocular Therapeutix), which is typically used after surgery for cataracts or glaucoma, I considered whether patients with an inflammatory eye condition who wear contact lenses might also benefit. The insert eliminates the need for daily topical medications by dispensing a tapered dose of preservative-free dexamethasone for 1 month. Although a bit of practice is needed, any eye care provider can place it into a patient’s lower punctum and then into canaliculus in the office.

This led me to collaborate with 2 colleagues to investigate the tolerability of the intracanalicular dexamethasone insert as a substitute for daily steroid drops in patients with keratoconus and comorbid inflammatory eye conditions. Our study, whose findings I presented at the annual meeting of the American Academy of Optometry in 2022, compared the insert against loteprednol etabonate ophthalmic gel 0.38% (Lotemax; Bausch + Lomb).

The study included 18 adult patients with bilateral keratoconus, dry eye, and allergic conjunctivitis who wore rigid contact lenses (corneal gas-permeable contact lenses or scleral lenses). Each received the intracanalicular dexamethasone insert in one eye; the loteprednol etabonate ophthalmic gel, whose dose was tapered down over a month, was applied to the other eye as a control.

Their progress (symptoms and signs) was evaluated at days 0, 7, 30, and 90, with the patients completing the Ocular Surface Disease Index (OSDI) at every visit and the Comparison of Ophthalmic Medications for Tolerability (COMTOL) questionnaire at their final visit.

Patients prefer the intracanalicular insert

Clinically, our team found that both treatments produced similar improvements in signs and symptoms of dry eye disease and allergy, with reductions in conjunctival papillary grade, tear film osmolarity, and corneal staining, as well as an improvement in tear break-up time. Across all the treated eyes in the study, the mean overall OSDI score was 48.6 ± 15.9 at the baseline screening exam and 33.7 ± 12.7 at the final visit.

However, patient satisfaction was much higher with the intracanalicular insert, and that is important for us to recognize as clinicians. At their 90-day visits, indicated via the COMTOL questionnaire, 88.9% of patients (n = 16) preferred the intracanalicular insert, whereas 11.1% of patients (2) preferred topical loteprednol. Of the patients who received the insert, 33.3% (6) reported rare instances of ocular itching and dryness, but when asked how bothered they were by these symptoms, 33.3% (2) replied “some” and 66.7% (4) replied “a little.” Meanwhile, 44.4% (8) of those who received topical loteprednol reported redness and dryness, 38.9% (7) tearing and itching, and 22.2% (4) problems with reading. Of the patients reporting symptoms, 25% (2) were bothered quite a bit by them, 37.5% (3) a little, and 37.5% (3) not at all.

These results suggest that the intracanalicular dexamethasone insert may enhance comfort and adherence in this patient population by eliminating the need to administer daily treatments that necessitate the removal of their contact lenses.

An extra benefit of the study was that participants were drawn from the patient population I treat, giving them access to a therapy they may not otherwise have been able to afford. I am always gratified when I can partner with industry to conduct research studies that enable underserved patients to receive the treatments they need.

Anticipating more sustained-release options

I am aware that my fellow optometrists are sometimes hesitant to prescribe steroids for patients with inflammation due to concerns about potential complications such as spikes in ocular pressure, especially in those with delicate corneas. But we have seen not only in this study but in others that steroids can help calm inflammation without producing those adverse effects.

When I presented my findings, a number of colleagues were surprised that a steroid insert could be used to treat patients outside a postoperative setting. But their overall response was quite positive, and I believe this project was a good reminder of the multiple tools available to treat patients with keratoconus and inflammation.

The introduction of time-released medications directly into the eye represents an exciting strategy in eye care. In addition to the intracanalicular dexamethasone insert, treatments delivered this way include a 9% intracameral dexamethasone intraocular suspension (Dexycu) that is administered at the time of surgery. Nonsteroidal options include an intracameral implant that administers bimatoprost (Durysta).

These kinds of delivery platforms constitute an important emerging paradigm for our patients, who face a unique constellation of barriers to the self-administration of prescribed eye drops.

Drugs such as the intracanalicular dexamethasone insert are a way to remove some of that burden, ensuring that patients benefit from the treatments they need to support both their eye health and their quality of life.

References

1. Harthan J, Bradley C, Nylin E. Patient tolerability of intracanalicular dexamethasone insert compared to topical loteprednol etabonate ophthalmic gel. Presented at: American Academy of Optometry Annual Meeting; October 25-31, 2022; San Diego, CA. Accessed June 5, 2023. https://aaopt.org/past-meeting-abstract-archives/?SortBy=&ArticleType=&ArticleYear=2022&Title=&Abstract=&Authors=harthan&Affiliation=&PROGRAMNUMBER=

2. Walters T, Bafna S, Vold S, et al. Efficacy and safety of sustained release dexamethasone for the treatment of ocular pain and inflammation after cataract surgery: results from two phase 3 studies. J Clin Exp Ophthalmol. 2016;7(4):572. doi:10.4172/2155-9570.1000572

3. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334-365. doi:10.1016/j.jtos.2017.05.003

4. Moran S, Gomez L, Zuber K, Gatinel D. A case-control study of keratoconus risk factors. Cornea. 2020;39(6):697-701. doi:10.1097/ICO.0000000000002283

5. Vandenbroeck S, De Geest S, Dobbels F, Fieuws S, Stalmans I, Zeyen T. Prevalence and correlates of self-reported nonadherence with eye drop treatment: the Belgian Compliance Study in Ophthalmology (BCSO). J Glaucoma. 2011;20(7):414-421. doi:10.1097/IJG.0b013e3181f7b10e