Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: A pilot study

Samanthila Waduthantri, Lei Zhou, Soon-Phaik Chee, Samanthila Waduthantri, Lei Zhou, Soon-Phaik Chee

Abstract

Purpose: To investigate the intra-cameral level of ganciclovir following topical application of ganciclovir gel, 0.15% for cytomegalovirus (CMV) anterior segment infection.

Design: Non-randomized, prospective, interventional clinical study.

Methods: Patients with active CMV anterior segment infection seen at Singapore National Eye Centre, confirmed by positive CMV real time PCR (RT-PCR) of the aqueous humor, that had not been treated with any form of ganciclovir in the preceding 1 month were recruited. They were treated with ganciclovir gel, 0.15% 1cc 5 times a day. Following 6 weeks of treatment, CMV load in the aqueous humor was measured using CMV RT-PCR and the ganciclovir drug levels in tears and aqueous humor were measured using high-performance liquid chromatography-mass spectrometry. The clinical features of the disease activity and the central corneal thickness (CCT) were recorded at the baseline and post-treatment.

Results: There were 29 eyes of 29 patients, of which 23 eyes had CMV anterior uveitis and 6 eyes had CMV endotheliitis. At the end of week 6, 26 eyes had undetectable CMV titre in the aqueous humor and no anterior chamber (AC) activity. Two patients had an increased CMV titre and increased AC inflammation. Both of these patients were non-compliant with the treatment. One patient had a reduced CMV titre in the aqueous humor with minimal AC inflammation. The mean ganciclovir concentration in the aqueous humor and the tears were 17.4 ± 30.6 ng/ml and 20,420.9 ± 33,120.8 ng/ml respectively. Mean CCT was 552.2 ± 42.3 microns. There was a weak correlation between the ganciclovir concentration in the aqueous humor and CCT (Spearmen's r = + 0.42, p = 0.025). There was no significant correlation between the ganiclovir concentration in the tears and CCT (Spearmen's r = + 0.39, p = 0.11).

Conclusion: Ganciclovir levels in the aqueous humor was below the 50% inhibitory dose (ID50) for CMV replication, following topical application of the ganciclovir gel, 0.15%.

Trial registration: SingHealth Centralized Institutional Review Board, Singapore; R733/17/2010, ClinicalTrials.gov; NCT01647529.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Participants’ flow diagram.
Fig 1. Participants’ flow diagram.
(CONSORT 2010 Flow Diagram from Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010; 340:c332).
Fig 2. Ganciclovir concentration in aqueous humor.
Fig 2. Ganciclovir concentration in aqueous humor.
Fig 3. Ganciclovir concentration in tears.
Fig 3. Ganciclovir concentration in tears.

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