Subconjunctival sirolimus in the treatment of autoimmune non-necrotizing anterior scleritis: results of a phase I/II clinical trial

Abstract

Purpose: To investigate the safety, tolerability and efficacy of subconjunctival sirolimus injections as a treatment for active, autoimmune, non-necrotizing anterior scleritis.

Design: Phase I/II, single-center, open-label, nonrandomized, prospective pilot study.

Methods: Five participants with active, autoimmune, non-necrotizing anterior scleritis with scleral inflammatory grade of ≥1+ in at least 1 quadrant with a history of flares were enrolled. A baseline injection was given, with the primary outcome measure of at least a 2-step reduction or reduction to grade zero in the study eye by 8 weeks. Secondary outcomes included changes in visual acuity and intraocular pressure, ability to taper concomitant immunosuppressive regimen, and number of participants who experienced a disease flare requiring reinjection. Safety outcomes included the number and severity of systemic and ocular toxicities, and vision loss ≥15 ETDRS letters. The study included 6 visits over 4 months with an extension phase to 1 year for participants who met the primary outcome.

Results: All participants (N = 5, 100%; 95% CI [0.60, 1.00]) met the primary outcome in the study eye by the week 8 visit. There was no significant change in mean visual acuity or intraocular pressure. Three out of 5 patients (60%) experienced flares requiring reinjection. No systemic toxicities were observed. Two participants (40%) experienced a localized sterile inflammatory reaction at the site of the injection, which resolved without complication.

Conclusions: Subconjunctival sirolimus leads to a short-term reduction in scleral inflammation, though relapses requiring reinjection do occur. There were no serious adverse events, though a local sterile conjunctival inflammatory reaction was observed.

Published by Elsevier Inc.

Figures

Figure 1

Response to treatment with subconjunctival sirolimus for the treatment of Autoimmune Non-Necrotizing Anterior Scleritis, Participant 1 The top panel, middle panel, and bottom panel show Participant 1 at Baseline, Week 2, and Week 52, respectively.

Figure 2

Adverse reaction with subconjunctival sirolimus for anterior scleritis, Participant 4 The left panel shows a sterile inflammatory reaction four days following a subconjuntival sirolimus injection. The right panel shows resolution of the reaction without complication.

Figure 3

Response to treatment with subconjunctival sirolimus for the treatment of Autoimmune Non-Necrotizing Anterior Scleritis, Participant 5 The top panel, middle panel, and bottom panel show Participant 5 at Baseline, Week 2, and Week 52, respectively.