The immunopathogenic mechanisms of dry eye disease (DED), one of the
most common ophthalmic conditions, is incompletely understood. Data from
this prospective, double-masked, randomized trial demonstrate that targeting
interleukin 1 (IL-1) by topical application of an IL-1 antagonist is
efficacious in significantly reducing DED-related patient symptoms and
To evaluate the safety and efficacy of treatment with the topical
IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having
DED associated with meibomian gland dysfunction.
Design and Setting
Prospective phase 1/2, randomized, double-masked, vehicle-controlled
Seventy-five patients with refractory DED.
Participants were randomized to receive treatment with topical
anakinra, 2.5% (n=30), anakinra, 5% (n=15), or vehicle (1%
carboxymethylcellulose) (n=30) 3 times daily for 12 weeks.
Main Outcomes and Measures
Primary outcomes were corneal fluorescein staining (CFS), complete
bilateral CFS clearance, dry eye–related symptoms as measured by the
Ocular Surface Disease Index, tear film breakup time, and meibomian gland
Topical anakinra was well tolerated compared with vehicle, with no
reports of serious adverse reactions attributable to the therapy. After 12
weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46%
reduction in their mean CFS score (P=.12 compared with
vehicle and P<.001 compared with baseline);
participants treated with anakinra, 5%, achieved a 17% reduction in their
mean CFS score (P=.88 compared with vehicle and
P=.33 compared with baseline); and patients treated
with vehicle achieved a 19% reduction in their mean CFS score
(P=.11). Complete bilateral CFS clearance was noted in
8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2of 29 patients
(7%) treated with vehicle (P=.03). By week 12, treatment
with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant
reductions in symptoms of 30% and 35%, respectively (P=.02
and P=.01, respectively, compared with vehicle); treatment
with vehicle led to a 5% reduction in symptoms.
Conclusions and Relevance
Treatment with topical anakinra, 2.5%, for 12 weeks was safe and
significantly reduced symptoms and corneal epitheliopathy in patients with
DED. These data suggest that the use of an IL-1 antagonist may have a role
as a novel therapeutic option for patients with DED.