Subconjunctival sirolimus-loaded liposomes for the treatment of moderate to severe dry eye disease

Abstract

Purpose : To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of signs and symptoms of patients with moderate to severe dry eye.

Methods : A randomized, triple-blind, phase II clinical trial. A total of 38 eyes of 19 patients were included. 9 patients (18 eyes) assigned to Sham group (Sham) and 10 patients (20 eyes) to Sirolimus-loaded liposomes group (Sirolimus). Methods: Treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and sham group received three doses of liposomal suspension without sirolimus. Main Outcomes Measures: Subjective (Ocular Surface Disease Index, OSDI) and objective (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer’s test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured pre- and post-treatment. Intragroup comparisons were performed (pre-treatment and post-treatment).

Results : Sirolimus-entrapped liposomes treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p= 0.0024), and conjunctival hiperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p <0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p= 0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p= 0.048). All the other evaluated outcomes only showed significant differences in the Sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted.

Conclusions : Our findings suggest that sub-conjunctival sirolimus-loaded liposomes is effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-severe dry eye disease, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects.

This is a 2021 ARVO Annual Meeting abstract.