Anterior Segment, Retina/Vitreous
Read Time: 2 mins

Ganciclovir in the Treatment of Ophthalmic Viral Infections – Case Reports

Published Online: June 21st 2012 US Ophthalmic Review, 2012;5(2):100-4 DOI: http://doi.org/10.17925/USOR.2012.05.02.100
Authors: John Affeldt, Neha Gadaria-Rathod, Karen B Fernandez, Penny A Asbell
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

Adenovirus is likely the most common cause of eye infections but remains a challenge for ophthalmologists to diagnose as well as treat. While ganciclovir gel is approved for the topical treatment of eye infections arising due to herpes simplex virus, it is not licensed for use against adenoviral conjunctivitis. This antiviral agent selectively targets infected cells and disrupts viral DNA replication. A small study and previous anecdotal reports had illustrated the potential of ganciclovir in improving symptoms and transmissibility of adenoviral eye infections. The present article describes a series of case studies where ganciclovir was used off label in the management of the morbidity caused by adenovirus. The observations are promising and suggest that ganciclovir can be used successfully in this patient population. However, large-scale randomised trials are needed to confirm these findings.

Keywords

Ganciclovir gel, adenoviral conjunctivitis, herpes simplex virus, off-label use, trifluridine toxicity, case studies

Article:

Eye infections are common and represent a major healthcare burden. Herpes simplex virus type 1 (HSV-1) and, less commonly, HSV type 2 (HSV-2) have been responsible for ocular infections in approximately 400,000 Americans. Moreover, nearly 50,000 new and recurring cases are diagnosed annually in the US with a quarter of cases being the more serious stromal keratitis.1 HSV is involved in the pathogenesis of several ocular disorders and may lead to numerous diseases including blepharitis, vesicular dermatitis of the eyelids, conjunctivits, keratitis, trabeculitis, anterior uveitis, acute retinal necrosis syndrome, retinitis and optic neuritis.2 Adenovirus, however, is the most likely cause of the majority of eye infections.

Adenoviral conjunctivitis is the most frequent cause of red eye and can lead to significant morbidity in patients. Although very common, it remains a challenge for ophthalmologists to both diagnose and treat, mainly because of its non-specific presentation and the numerous conditions that can cause pink eye. Aside from the difficulties in diagnosis and treatment of patients, contagiousness and easy transmission to family members is part of the challenge. At present, clinicians generally only offer supportive measures to treat these patients.

Ganciclovir is an antiviral agent that is selectively active against viral DNA. This prodrug is a synthetic nucleoside analog of 2’-deoxyguanosine 9-(1,3-dihydroxy-2-propoxymethyl) guanine that is phosphorylated by the virus-encoded thymidine kinase.2 Ganciclovir triphosphate then competitively inhibits incorporation of the endogenous nucleotide by the viral DNA polymerase. This results in replication arrest and damage to infected cells. Ganciclovir is currently approved by the US Food and Drug Administration to be used systemically and intravitreally against cytomegalovirus retinitis and, following positive results from clinical trials, topically (Ganciclovir ophthalmic gel; Zirgan®) against herpes simplex dendritic keratitis.3 Topical application of ganciclovir has been shown to penetrate the corneal stroma and reach the aqueous humor at therapeutic levels.4

In May 2011, Yabiku and colleagues reported results of a double-blind, randomized clinical trial of 33 patients diagnosed with adenoviral conjunctivitis.5 They compared the efficacy of ganciclovir ophthalmic gel against placebo in reducing and improving signs, symptoms and transmissibility. They found a trend to faster improvement and less transmissibility to the other eye and people living with affected patients in the treatment group, however these data were not statistically significant.

To view the full article in PDF or eBook formats, please click on the icons above.

Article Information:
Disclosure

Penny A Asbell has been a consultant for Alcon, Aton, Bausch & Lomb, Inspire, Johnson & Johnson, Merck, Pfizer, Santen and Vistakon Pharma, has received research funding from the National Institutes of Health, Research to Prevent Blindness, the Toni and Martin Sosnoff Fund, Bausch & Lomb, Alcon and Inspire, and has received educational grants from Santen and Inspire. The remaining authors have no conflicts of interest to declare.

Correspondence

Penny A Asbell, Professor of Ophthalmology and Director of Cornea and Refractive Services, Department of Ophthalmology, Mount Sinai School of Medicine, New York, US. E: johnaffeldt@aol.com, penny.asbell@nyc.rr.com

Support

The publication of this article was funded by Bausch & Lomb. The views and opinions expressed are those of the authors and not necessarily those of Bausch & Lomb.

Received

2012-08-05T00:00:00

References

  1. National Eye Institute – National institutes of health, facts about the cornea and corneal disease. Available at: www.nei.nih.gov/health/cornealdisease/#k (accessed 16 Aug 2012).
  2. Tabbara KF, Al Balushi N, Topical ganciclovir in the treatment of acute herpetic keratitis, Clin Ophthalmol, 2010;4:905–12.
  3. US Food and Drug Administration, Center for Drug Evaluation and Research. NDA Application 22-211. 2010. Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022211_ zirgan_toc.cfm (accessed 16 Aug 2012).
  4. Castela N, Vermerie N, Chast F, et al., Ganciclovir ophthalmic gel in herpes simplex virus rabbit keratitis: intraocular penetration and efficacy, J Ocul Pharmacol, 1994;10:439–51.
  5. Yabiku ST, Yabiku MM, Bottos KM, et al., Ganciclovir 0.15 % ophthalmic gel in the treatment of adenovirus keratoconjuntivitis, Arq Bras Oftalmol, 2011;74:417–21.
  6. Colin J, Ganciclovir ophthalmic gel, 0.15 %: a valuable tool for treating ocular herpes, Clin Ophthalmol, 2007;1:441–53.
  7. Kaufman HE, Adenovirus advances: new diagnostic and therapeutic options, Curr Opin Ophthalmol, 2011;22:290–3.
  8. Sambursky R, Tauber S, Schirra F, et al., The RPS adeno detector for diagnosing adenoviral conjunctivitis, Ophthalmology, 2006;113:1758–64.
  9. Skevaki CL, Galani IE, Pararas MV, et al., Treatment of viral conjunctivitis with antiviral drugs, Drugs, 2011;71:331–47.
  10. Hillenkamp J, Reinhard T, Ross RS, et al., The effects of cidofovir 1 % with and without cyclosporin a 1 % as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study, Ophthalmology, 2002;109:845–50.
  11. Romanowski EG, Yates KA, Gordon YJ, Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model, Antiviral Res, 2001;52:275–80.
  12. Colin J, Hoh HB, Easty DL, et al., Ganciclovir ophthalmic gel (Virgan; 0.15 %) in the treatment of herpes simplex keratitis, Cornea, 1997;16:393–9.
  13. Hoh HB, Hurley C, Claoue C, et al., Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study, Br J Ophthalmol, 1996;80:140–3.
  14. Chen FE, Liang RH, Lo JY, et al., Treatment of adenovirusassociated haemorrhagic cystitis with ganciclovir, Bone Marrow Transplant, 1997;20:997–9.
  15. Bruno B, Gooley T, Hackman RC, et al., Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival, Biol Blood Marrow Transplant, 2003;9:341–52.
  16. Gordon YJ, Romanowski E, Araullo-Cruz T, et al., Inhibitory effect of (S)-HPMPC, (S)-HPMPA, and 2'-nor-cyclic GMP on clinical ocular adenoviral isolates is serotype-dependent in vitro, Antiviral Res, 1991;16:11–6.
  17. Kinchington PR, Romanowski EG, Jerold Gordon Y, Prospects for adenovirus antivirals, J Antimicrob Chemother, 2005;55:424–9.
  18. Tabbara KF, Jarade E, Ganciclovir effects in adenoviral keratoconjunctivitis, ARVO, 2001;(Suppl.)S579:Abstract 3111.

Further Resources

Share this Article
Related Content In Retina/Vitreous
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72