Epinephrine distribution after topical administration to phakic and aphakic eyes

Not infrequently an important clinical drug is found to have side-effects far beyond those initially anticipated. Epinephrine, administered topically in the management of open-angle glaucoma, effectively lowers intraocular pressure, but it has side-effects which may be both local and systemic. As a first approach to the understanding of these widespread effects, the present studies report the specific distribution of radioactivity labeled epinephrine--after it is applied topically to one eye--in the same eye, the opposite eye, and in other certain nonocular tissues. Further, because of the existence of the clinical syndrome known as "aphakic epinephrine maculopathy," similar measurements of distribution of labeled epinephrine after topical administration are reported for aphakic eyes. Autoradiography is used to localize radioactive epinephrine specifically within tissues histologically, and radiochromatography is used to confirm specific association of radioactivity with chemically authentic epinephrine. In general, after topical administration, the exogenously administered epinephrine is taken up and stored substantially in the iris and ciliary body and to a lesser extent in the choroid in the treated eye. If the treated eye is aphakic, significantly more labeled epinephrine appears in the choroid. Far less epinephrine is found in the retina and still less in the optic nerve of the treated eye, but uptake and storage in these tissues also increases substantially in the treated eye if the eye is aphakic. Very small but definitely measurable and identifiable amounts of epinephrine also appear in the tissues of the opposite eye, again in similar proportions. There is no difference in the amount of epinephrine which appears in the opposite eye if either or both eyes are aphakic. Significant amounts of epinephrine are also seen in nonocular tissues such as those of the heart and spleen following topical administration. While these findings do not speak to the mechanism of epinephrine side-effects on the anterior eye, the posterior eye, the opposite eye, or on systemic tissues and organs, they do address the possibility that epinephrine can cause side-effects in these areas by demonstrating its localization there following topical administration. These findings have clinical implications relevant to glaucoma management, to toxic ocular syndromes such as epinephrine maculopathy in aphakia, and to toxic systemic effects of epinephrine.