Effects of various concentrations of diethylcarbamazine citrate applied as eye drops in ocular onchocerciasis, and the possibilities of improved therapy from continuous non-pulsed delivery

Abstract

Diethylcarbamazine was given as eye drops in varying concentrations in a half-log dilution series from 1.0 to 0.0001% to patients with ocular onchocerciasis. Migration of microfilariae into the cornea, followed by their straightening and disintegration, was observed with delivery rates as low as 0.1 microgram/hour. Dose-related adverse inflammatory reactions, including the development of globular limbal infiltrates with itching and redness, were seen with delivery rates as low as 0.6 microgram/hour, but substantial inflammatory reactions, including severe vasculitis, were seen only with delivery rates of or above 1.0 microgram/hour. This suggests that it should be possible to achieve beneficial clearing of the microfilarial load, without adverse reactions, by continuous non-pulsed delivery of the drug. Technology exists for such delivery, either directly into the eye or systemically by a transdermal system that could give 3 to 7 days' treatment from each application. The observations reported suggest that after preliminary clearing of the microfilarial load by carefully controlled delivery of DEC it may be possible to maintain therapy by less strictly controlled delivery in DEC-medicated salt, or to use treatment with suramin, without incurring substantial adverse reactions, such as a deterioration in vision in cases in which the optic nerve is already compromised. Continuous non-pulsed DEC delivery systems could have a place in the management of onchocercal sclerosing keratitis. The unique opportunities for using the ocular model to define the requirements for beneficial non-damaging therapy with DEC should be explored in further field trials.