Safety of subconjunctival injection of mesenchymal stromal cells in persistent corneal epithelial disease - A phase 1b clinical trial.

PURPOSE: To investigate the safety and tolerability of subconjunctival injection of three escalating doses of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in patients with persistent corneal epithelial defect/disease (PCED).

DESIGN

Prospective single-center open label phase 1b clinical trial.

PARTICIPANTS

Patients with PCED in the setting of neurotrophic keratitis and/or limbal stem cell deficiency.

METHODS

A dose escalation study design was used. The first three patients received a subconjunctival injection of 1 × 106 MSCs/50 μL suspension; subsequently, three participants were treated with 1 subconjunctival injection of 3 × 106 MSCs/150 μL; and two participants received 2 subconjunctival injections of 3 × 106 MSCs/150 μl in 2 conjunctival sites.

MAIN OUTCOME MEASURES: The primary outcome was the safety of the treatment determined on day 28 post-injection. Ocular surface toxicity and other ocular or systemic treatment emergent adverse events (TEAEs) were assessed at 1, 7, 14, 28 and 90 days. Demonstration of safety on day 28 was required before escalating to the next higher dose. Changes in the PCED were also monitored.

RESULTS

Eight participants completed the 90-day study. All 3 doses of subconjunctival MSCs were well tolerated. No participant developed ocular surface toxicity or other ocular or systemic TEAEs. The size of the PCED improved in 5 (63 %) patients; it increased in 2 (25 %) patients; and no progressive improvement was observed with dose escalation.

CONCLUSION

Subconjunctival administration of MSCs was safe and well tolerated with no systemic or ocular toxicity in patients with PCED. Improvement in epithelial defect size was observed in 63 % of the participants.