EVALUATING DELAYED CONTACT HYPERSENSITIVITY REACTIONS FROM OCULAR MEDICATIONS

An approach for evaluating drugs as contact ocular allergens is propos ed that includes the evaluation of compounds in a sensitization test w ith dermal and ocular challenges in addition to the required ocular ir ritation studies. Five compounds reported as contact ocular sensitizer s in humans or animals were evaluated using this model: atropine, neom ycin, phenylephrine, and experimental formulas L-645,151, and L-653,32 8. All five gave positive results upon skin and ocular challenge. Atro pine, L-645,151, and L-653,328 demonstrated adverse ocular reactions a fter long-term administration in the ocular irritation studies, The cl inical and microscopic appearance of the ocular reactions in guinea pi gs, rabbits, and dogs was also defined. Topical ocular irritation stud ies required in the development of ophthalmic agents do not always det ect adverse ocular reactions evidenced in humans. The guinea pig maxim ization test (GPMT) with skin or ocular challenge identifies qualitati vely potential contact ocular allergens. By using both long-term ocula r application and the GPMT, predicting which drugs will have a greater ability to induce adverse ocular reactions is enhanced.