Pathological Features of Corneal Phospholipidosis in Juvenile White Rabbits Induced by Ocular Instillation of Chloroquine or Amiodarone

Cationic amphiphilic drugs (CADs) can induce phospholipidosis (PLD) in organs/tissues. Several ophthalmic pharmaceuticals containing CADs are marketed and used in children. To investigate the effect of PLD on the developing cornea, chloroquine and amiodarone, which are representative CADs, were applied topically to the eyes of juvenile rabbits, and the effects in juvenile rabbits were compared with those in young adult rabbits. Diffuse corneal cloudiness was observed in chloroquine- and amiodarone-treated eyes. Histopathologically, vacuolation was observed in the corneal epithelium and keratocytes. On ultrastructural examination, these vacuoles contained multilamellar inclusion bodies, which are a characteristic of PLD. The size of the vacuoles in the corneal epithelium was reduced in juveniles compared with young adults. Cytoplasmic lamellar bodies and exocytosis in the corneal endothelium were observed in young adult rabbits but not in juvenile rabbits. This study revealed that topical application of chloroquine or amiodarone induces corneal PLD in juvenile and young adult rabbits. Corneal endothelial changes occurred only in young adult rabbits, but ophthalmological changes were similar between juveniles and young adults. The results of the study suggest that the effects of corneal PLD were similar among age groups based on risk assessment.