Instillation of epinephrine bitartrate, borate, and hydrochloride solutions in various clinically used strengths failed to produce corneal melanin pigmentation in rabbit eyes. Continuous exposure to the experimental drug using saturated Czech soft gel contact lenses also failed to induce pigmentation in the intact rabbit cornea. Repeated elevation of intraocular pressure by subconjunctival injection of hypertonic sodium chloride solution and abrasion of corneal epithelium resulted in pigment deposition. The appearance of pigment was obtained very much earlier with the use of oxidized epinephrine preparations. In the earliest stages, the pigment was detected only by histological examination. At later stages, slit-lamp biomicroscopy revealed the pigmentation, which eventually could be recognized on gross inspection.
Krejci L, Harrison R. Corneal Pigment Deposits From Topically Administered EpinephrineExperimental Production. Arch Ophthalmol. 1969;82(6):836-839. doi:10.1001/archopht.1969.00990020828020