Ocular safety of subconjunctival injection of tacrolimus in rabbits

The main aim of this study was to evaluate the safety of subconjunctival injection of tacrolimus in rabbit eyes. Ten white New Zealand rabbits were included. A concentration of tacrolimus 0.03% was prepared for subconjunctival injection. Tacrolimus 0.03% was compounded by adding water for injection solution to 1,000 µg tacrolimus capsule (Prograf; Astellas Pharma Inc., Tokyo, Japan) to achieve 0.03% concentration. Prograf capsule inactive ingredients (excipients) inside the core included hypromellose, croscarmellose sodium, lactose monohydrate, and magnesium stearate. Tacrolimus 0.03% was injected subconjunctivally in one eye of each rabbit and water for injection solution was injected subconjunctivally into the contralateral eye. All rabbits underwent ocular examination in the 1st, 3rd, 10th and 30th day after injection. The following parameters were evaluated: tearing, hyperemia, conjunctival chemosis, and scleral necrosis/discoloration. The rabbits were sacrificed 30 days after injections and histopathological examination was performed on enucleated eyes. No tearing or scleral necrosis/discoloration was observed in either group. In the tacrolimus-injected eyes, conjunctival hyperemia and chemosis were minimal compared to the water-injected control eyes, where severe hyperemia was noted initially but improved over time. Histopathological examination revealed less lymphocytic infiltration and better-preserved scleral and corneal structures in the tacrolimus group. Subconjunctival tacrolimus demonstrated a promising safety profile. No serious adverse events were noted clinically or pathologically.