New canalicular gel shows promise for dry eye treatment

Image by Jennifer Toomey / MJH Life Sciences using AI

Reviewed by Mark Packer, MD; and Eric Donnenfeld, MD

In June 2024, a canalicular gel device (Lacrifill, Nordic Pharma) was introduced to the US market, and a recent study has shown it to be a safe, well-tolerated, and effective treatment for dry eye.¹ This device offers a new option for managing a condition that affects millions of patients.

A study, led by first author Mark Packer, MD, president of Packer Research Associates in Fort Collins, Colorado, reported that the use of the device resulted in clinically and statistically significant improvements in the signs and symptoms of dry eye that were sustained through 6 months.

“Lacrifill provides a novel approach to lacrimal occlusion without the negative effects of punctal plugs, such as spontaneous extrusion, which occurs in 40% of patients, and ocular surface irritation, which occurs in 10% of patients,” Packer said. “In addition, because Lacrifill completely fills the canaliculus, there is no space for stagnant tears and mucus that may lead to infection. Lacrifill makes lacrimal occlusion a truly appealing modality for the treatment of dry eye symptoms, irrespective of etiology.”

How the gel device works

Lacrifill Canalicular Gel is a chemically crosslinked particulate hyaluronic acid (HA) hydrogel intracanalicular occlusion device that blocks drainage of tears by occluding the canalicular system. The investigators explained that the gel-like material fills the lumen, thereby preventing tear flow through the lacrimal drainage system. The device is intended to be used for up to 6 months to treat the symptoms of dry eye.

While the second-line treatments for dry eye, lacrimal occlusive devices (punctal plugs), reduce tear outflow, increase ocular surface moisture, and are more convenient compared with artificial tears, patients may report a foreign body sensation, and the plugs have the potential to fall out and to abrade the cornea.

The investigators explained that conventional canalicular plugs are positioned inside the canaliculus and are not visible but may not fully obstruct tear drainage because the canaliculus varies in diameter among patients.

“The ideal canalicular occlusion device for dry eye would fully block the lacrimal drainage system; have straightforward placement; be easily removed when necessary; and be comfortable, durable, biocompatible, and safe with a low potential for infection,” the investigators wrote.

According to the investigators, HA is a substance produced naturally in the human body as a component of the tear film, outer cornea, and vitreous humor, and has important functions throughout the body.^2,3 At the ocular surface, HA has lubricating, anti-inflammatory, antioxidant, and antitoxic effects.²

Accordingly, HA is a useful component in artificial tears and has a proven safety record.² Crosslinking-free HA molecules form a durable gel that withstands degradation unless subjected to external shear force.³ Thus, crosslinked HA is an excellent material for an intracanalicular occlusion device, the investigators explained.

“The design of Lacrifill allows for rapid and easy insertion of the crosslinked hyaluronic canalicular gel through the punctum into the canaliculus at the slit lamp or under an operating microscope and can be performed in minutes,” said Eric Donnenfeld, MD, clinical professor of ophthalmology at New York University Medical Center and a private practitioner in Garden City, New York.

Multicenter comparative study: Methods and results

The researchers conducted a prospective, multicenter, double-masked, randomized controlled trial to assess the effectiveness and safety of the Lacrifill Canalicular Gel device compared with the Form Fit Hydrogel Intracanalicular Plug (Oasis Medical). The Form Fit plug was selected for comparison due to its similar intracanalicular occlusion design.

Participants included adults with dry eye who met the following criteria: an anesthetized Schirmer test result of 10 mm or less within 5 minutes, corneal staining, an ocular surface disease index (OSDI) score of 23 or higher with 3 or fewer responses of “not applicable,” a patent lacrimal drainage system, and corrected distance visual acuity of 20/40 or better in both eyes.

The procedure involved applying topical anesthesia, followed by flushing the lower puncta with saline to verify patency. A syringe prefilled with crosslinked HA filler was attached to a cannula, which was inserted into the lower punctum. About 0.2 mL of the crosslinked HA filler was injected into each canaliculus.

The device was removed at 6 months by irrigating the lower canaliculus with sterile saline until it freely flowed through the drainage system and/or the patient reported swallowing or fluid sensation in the nose and throat.

The hydrogel plug was placed bilaterally in the vertical portion of the inferior canaliculus according to the manufacturer’s instructions.⁴

The primary effectiveness end point for patients treated with filler compared with plugs was noninferiority of the mean within-subject change from baseline to month 3 in the Schirmer score. The secondary effectiveness end point was the noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional end points were the mean changes from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety, the investigators recounted.

At the 6-month mark, the device was removed by irrigating the lower canaliculus with sterile saline until the solution flowed freely through the drainage system or the patient reported a sensation of fluid in the nose or throat, indicating successful drainage.

The hydrogel plug was inserted bilaterally into the vertical portion of the inferior canaliculus following the manufacturer’s guidelines.⁴

The primary effectiveness end point was the noninferiority of the mean change in Schirmer scores from baseline to 3 months between patients treated with filler versus plugs. A secondary end point was the noninferiority of the proportion of patients treated with filler who achieved a clinically significant improvement in OSDI scores from baseline to month 3. Moreover, additional end points included mean changes from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety, according to the investigators.

A total of 157 patients were randomized to 1 of the treatments: 99 to the filler and 52 to hydrogel plugs, with all completing the study.

“At month 3, the crosslinked HA filler group was statistically noninferior and numerically superior to the hydrogel plug group in the anesthetized Schirmer test score change from baseline, with a noninferiority margin of <2.5 mm,” the authors reported.

Both treatment groups had significantly improved Schirmer scores at 3 and 6 months compared with baseline. In the filler and plug groups, respectively, the changes from baseline at 3 months were 3.9 ± 7.6 mm (P < .0001) and 1.9 ± 5.0 mm (P = .0047). At 6 months, the respective changes were 3.8 ± 6.7 mm (P < .0001) and 1.8 ± 4.0 mm (P = .0009).

The filler was also noninferior to the plug in the proportion of patients achieving clinically meaningful improvement from baseline to month 3 in OSDI score (84.3% and 83.3%, respectively; P = .0004).

The OSDI score significantly improved from baseline to months 3 and 6 in both groups. At 3 months, the respective changes from baseline were 27.3 ± 20.3 (P < .0001) and 25.3 ± 16.2 (P < .0001); at 6 months, the respective changes were 25.3 ± 20.1 (P < .0001) and 23.9 ± 19.0 (P < .0001).

The secondary end points evaluated—tear meniscus height, OSDI, corneal staining, tear breakup time, and safety—did not differ between the 2 treatments.

The investigators noted that crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye.

“The crosslinked HA filler effectively occludes the canaliculi, maintaining lubricating natural tears on the surface of the eye,” they concluded. “There were clinically and statistically significant improvements in both signs and symptoms of dry eye, which were sustained through 6 months. The crosslinked HA filler will be useful in a wide population of patients with dry eye, including those undergoing cataract and refractive surgeries.”

References:

1. Packer M, Lindstrom R, Thompson V, et al. Effectiveness and safety of a novel crosslinked hyaluronate canalicular gel occlusive device for dry eye. J Cataract Refract Surg.2024;50(10):1051-1057. doi:10.1097/j.jcrs.0000000000001505 PMID: 38875184.

2. Hynnekleiv L, Magno M, Vernhardsdottir RR, et al. Hyaluronic acid in the treatment of dry eye disease. Acta Ophthalmol. 2022;100(8):844-860. doi:10.1111/aos.15159. PMID: 35514082; PMCID: PMC9790727.

3. Posarelli C, Passani A, Del Re M, et al. Cross-linked hyaluronic acid as tear film substitute. J Ocul Pharmacol Ther. 2019;35(7):381-387. doi:10.1089/jop.2018.0151.

4. Form Fit hydrogel canalicular plug. Instructions for use. Oasis Medical. 2022. Accessed April 30, 2024. https://www.oasismedical.com/wp-content/uploads/2024/01/FORM-FIT%C2%AE-Intracanalicular-Plug-Instructions-For-Use.pdf