Cross-Linked Hyaluronic Acid Gel For Lacrimal Occlusion In The Treatment Of Dry Eye Disease: Results Of The United States Food And Drug Administration Clinical Investigations

To evaluate the safety and effectiveness of cross-linked hyaluronic acid (HA) gel for lacrimal occlusion and improvement of the signs and symptoms of dry eye disease.  The ideal canalicular occlusion device should be biocompatible, reversible, repeatable, safe and have a low complication rate. Cross-linked HA meets these criteria. Cross-linking free HA chains creates a robust gel that is resistant to degradation. Synthetically cross-linked hyaluronic acid forms a hydrogel that is 98% water. It is sufficiently soft to conform to the delicate inner walls of the canaliculus and block tear outflow. The very small particles of the gel form a cohesive structure consisting of particles that stick together with enough force to remain intact.

Multicenter clinical trial conducted at six sites in the United States

Prospective, multicenter, randomized, double masked, controlled, clinical study to evaluate the clinical utility and safety of cross-linked hyaluronic acid gel (Lacrifill, Nordic Pharma) compared to a commercially available canalicular plug over 6 months of subject follow-up.  Subjects with anesthetized Schirmer score ≤ 10 mm, Ocular Surface Disease Index (OSDI) score ≥ 23, presence of corneal staining and patent bilateral lacrimal drainage systems were randomized in a 2:1 ratio to Lacrifill or a hydrogel intracanalicular plug (Form Fit Hydrogel Canalicular Plug, Oasis Medical).  Subjects with any ocular condition that, in the opinion of the investigators, would interfere with the interpretation of study results were excluded.   

157 (mean age 62.9 ± 11.7 years, 118 female) subjects were randomized. 26 subjects (16.6%) had undergone LASIK and 25 (15.9%) had undergone cataract surgery. In the Lacrifill group (n = 99) at 3 and 6 months, respectively, mean Schirmer improved from 5.4 to 8.7 and 8.9 mm, OSDI improved from 48.3 to 21.4 and 23.7, corneal staining (NEI score) improved from 5.9 to 3.9 and 3.6, and tear break up time improved from 3.0 to 3.8 and 4.0 seconds. In the Oasis group (n = 52), Schirmer improved from 5.5 to 7.6 and 7.5 mm. The most frequent adverse events were increased staining (Lacrifill, 7.8%; Oasis, 16.7%), tearing (7.8%, 5.6%) and discomfort during insertion (5.8%, 5.6%).  Planned removal of Lacrifill at 6 months by irrigation was rated easy.  

Dry eye disease remains a significant unmet medical need and represents a particular challenge for cataract and refractive surgeons, whose patients face potential worsening of signs and symptoms postoperatively. Cross linked HA gel represents a novel, safe and effective approach to lacrimal occlusion for the treatment of dry eye disease. Significant improvements from baseline were observed for both signs and symptoms of dry eye disease, including Schirmer, OSDI, corneal staining and tear break up time. There was a trend towards superiority to the control in Schirmer score at 1, 3 and 6 months and in corneal staining at 6 months. There were no serious or unanticipated adverse events. The US FDA approved Lacrifill based on this study.