Noninvasive detection of ganciclovir in ocular tissue by raman spectroscopy: Implication for monitoring of drug release

Treatment of various pathological conditions in ophthalmology, such as cytomegalovirus (CMV) retinopathy and endophthalmitis, requires a local drug intervention rather than a systemic approach. Accurate knowledge of intraocular drug concentration can permit the ophthalmologist to maintain drug levels within the therapeutic levels necessary for an optimal prognosis, while preventing or minimizing toxicity associated with drug overdose. Purpose To develop a noninvasive/noncontact method for quantification of the local concentration of ganciclovir in the ocular media. Methods An integrated CCD-based Raman spectroscopic system designed specifically for ophthalmic applications was used to noninvasively detect the presence of ganciclovir in the ocular media. Various known concentrations of ganciclovir were injected into the aqueous humor of rabbit eyes in a pilot study, in vivo. Raman spectra were then acquired by focusing an argon laser beam within the anterior chamber of the eye. The specific Raman signature of ganciclovir was assessed at several concentrations. Results Spectral features unique to ganciclovir were identified and distinguished from those of ocular tissue. The amplitudes of the spectral peaks corresponding to ganciclovir exhibited a linear dependence on the local concentration of the drug in the anterior chamber of the eye. Conclusion Raman spectroscopy may offer an effective tool for the noninvasive assessment of the local concentration of ganciclovir in the ocular media. This technique offers the potential to determine both the amount and the rate of the drug release from implants designed to deliver antiviral drugs locally within the eye. The availability of such data could enable the ophthalmologist to improve treatment efficacy by avoiding premature or late surgical replacement of the implants.