ToF-SIMS Analysis of Dexamethasone Distribution in the Isolated Perfused Eye

PURPOSE. To illustrate the ability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to characterize and demonstrate the spatial distribution of dexamethasone within ocular tissues.METHODS. Dexamethasone sodium phosphate was administrated to perfused and nonperfused ovine eyes via intravitreal injections. The vitreous humor, the lens, and the retina of the eyes were then removed and divided into front, middle, and back sections. ToF-SIMS analysis was performed on each cross-section of the vitreous humor using Bi3+ cluster source and images of drug distribution within the sections generated.RESULTS. In the positive ion spectra, four key drug fragment peaks were identified and in the negative ion spectra, one key drug peak was identified. All five important drug peaks were successfully imaged in each tissue section and their distribution within the section illustrated. The drug was shown in the nonliving eye to move by diffusion alone, whereas in the living eye the drug was shown to distribute faster within the vitreous and penetrate through to the back of the retina and also into the lens.CONCLUSIONS. The results illustrate the ability of ToF-SIMS to characterize and provide spatial information about drug distribution within ocular tissues. Key differences in drug movement through the vitreous humor, toward both the anterior and the posterior tissues, in the living eye and the nonliving ovine eye were demonstrated, showing that dexamethasone sodium phosphate distribution through the vitreous is not determined by diffusion alone. (Invest Ophthalmol Vis Sci. 2011;52:8413-8419) DOI: 10.1167/iovs.11-8199