Minimally invasive, direct, real time measurement of drug concentration in the anterior eye

Miller, J. and Wilson, W. S. and Wilson, C.G. and Uttamchandani, D. (2005) Minimally invasive, direct, real time measurement of drug concentration in the anterior eye. British Journal of Ophthalmology, 89 (9). pp. 1147-1151. ISSN 0007-1161 (https://doi.org/10.1136/bjo.2004.060780)

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Abstract

The aim of this study was to evaluate a corneal contact lens which effectively turns the anterior chamber of the eye into a cuvette, enabling the concentration of a drug to be measured using absorption spectroscopy. A hand held contact lens incorporating optical fibres connected to a spectrograph enabled a beam of light to be directed in, across, and out of the anterior chamber. The device was used to follow the time course of drug concentration in the anterior chamber of rabbit (sedated) and humans, using topical brimonidine or fluorescein (with or without local anaesthesia). Absorbance measurements were taken for a 5-25 second period, repeated every 30 minutes. Drug concentrations were compared using absorbance peak height. Corneal absorption starts to rise rapidly at wavelengths shorter than 315 nm. The light path within the anterior chamber is 6.9 mm (rabbit) and 5.8 mm (human), the absorbance measured also includes a corneal component. Application of fluorescein (three drops of 2% solution) in rabbit allowed detection, 60 minutes later, of a large absorbance peak at 490 nm. In the human eye, the device could not measure fluorescein (applied as in rabbit), but clearly detected brimonidine for 3 hours following topical application of 0.6 mg. Modification of the device to measure fluorescence resulted in the detection of 5.3 nM fluorescein in the ex vivo rabbit eye, an increase in sensitivity of two orders of magnitude over the absorption measurements. This device has the potential to allow repeated measurements of drug concentrations in the anterior eye provided the drug has suitable absorption or fluorescence characteristics.

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