Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

Abstract

Objectives: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina.

Methods: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision.

Results: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes.

Conclusions: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.

Figure 1

Acyclovir concentrations in the vitreous at different time points after intravitreal injection.

Figure 2

Representative ERG recordings of the eyes of one animal at different time points [dark-adapted (30 cd.s/m²) and light-adapted (3 cd.s/m²) states].

Figure 3

Response versus log light intensity (VlogI) curve of the eyes that were injected with acyclovir and saline solution. The gray area represents the mean ±1 standard deviation of the b-wave amplitude of the eyes that were injected with saline solution.

Figure 4

b-wave to a-wave (dark-adapted state, 30 cd.s/m²) correlations between the eyes that were injected with acyclovir and saline at different time points. Each point represents the a- and b-wave amplitudes from one eye.