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Herpes Simplex Keratitis Medication

  • Author: Jim C Wang (王崇安), MD; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Dec 07, 2015

Medication Summary

Topical corticosteroids are effective in suppressing the inflammatory response of herpetic keratitis. However, their inappropriate use may result in severe epithelial disease or stromal necrosis, corneal perforation, increased tendency toward recurrence, secondary microbial infections, elevation of the intraocular pressure, and lenticular changes.

Patients requiring topical corticosteroids for suppression of the inflammatory response usually require the drug for a period of months, and withdrawal often is complicated by a recurrence of inflammation. The immunosuppressive complications of steroid administration (eg, recurrent epithelial disease) largely can be avoided by the concurrent administration of antiviral therapy.

Patient cooperation is a prerequisite for the safe administration of corticosteroids in herpetic keratitis. An extremely slow corticosteroid taper typically is required.

Antiviral agents, topical or oral, are prescribed to inhibit viral replication in infected cells. All topical antiviral medications available for clinical use in the United States are toxic, with signs of toxicity being similar for all such drugs. Punctate epithelial keratopathy, limbal follicles, a follicular conjunctival response, ptosis, punctal stenosis, and contact dermatitis can occur at any time after 10-14 days of therapy.

In mild cases of antiviral toxicity, epithelial changes may be the only manifestation. The toxic potential of antiviral agents always should be considered in patients who heal poorly, because these agents are inhibitors of cell division.[40]


Antiviral agents

Class Summary

These agents inhibit herpes simplex virus (HSV) replication. Treatment of viral infections begins with mechanical débridement of the involved rim along with a rim of normal epithelium. This is followed by the topical instillation of antiviral medications (eg, trifluridine, ganciclovir).[41]

Trifluridine ophthalmic solution 1% (Viroptic)


A structural analogue of thymidine, this agent inhibits viral DNA polymerase. Viroptic has better penetration through the cornea and greater efficacy (95% heal rate) than other topical agents. If no response occurs in 7-14 days, consider other treatments.

Valacyclovir (Valtrex)


Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir. It produces a greater serum concentration of acyclovir with smaller oral dosing. Valacyclovir is more expensive than acyclovir but can be as effective with a more convenient dosing regimen.[19] The optimal dose for ocular disease has not been determined.

Famciclovir (Famvir)


This agent is a prodrug that, when biotransformed into its active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. It has been used successfully in the suppression of genital herpes. Its efficacy in HSV keratitis currently is under study.

Acyclovir (Zovirax)


Acyclovir is a synthetic guanosine analogue that requires activation by viral thymidine kinase. The activated acyclovir triphosphate, concentrated 50-100 times in HSV-infected cells, suppresses viral replication by preferentially inhibiting viral DNA polymerase, serving as a DNA chain terminator and inducing irreversible binding between polymerase enzyme and the interrupted DNA chain.

Acyclovir is a potent inhibitor of viral growth with minimal toxicity to uninfected epithelial cells. Oral acyclovir at a dose of 2 g/day for 10 days has been reported to be as effective as topical agents for epithelial keratitis, with the advantage of no ocular toxicity.

Ganciclovir ophthalmic gel 0.15% (Zirgan, Vitrasert)


This agent is an acyclic nucleoside analogue of 2'deoxyguanasine. It phosphorylates first to monophosphate form by a viral-encoded protein kinase homologue, and then to diphosphate and triphosphate forms by cellular kinases. This allows for greater concentration of ganciclovir in virus-infected cells, possibly because of preferential phosphorylation of this agent in infected cells.

Ganciclovir is thought to inhibit HSV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. Like acyclovir, ganciclovir is virostatic and exerts its effect only on replicating virus.

Contributor Information and Disclosures

Jim C Wang (王崇安), MD Vitreo-Retinal and Cornea/Anterior Segment Subspecialist, Department of Ophthalmology, Kaiser Permanente Fontana Medical Center

Jim C Wang (王崇安), MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, American Society of Cataract and Refractive Surgery

Disclosure: Nothing to disclose.


David C Ritterband, MD, FACS Assistant Director of Cornea Service, New York Eye and Ear Infirmary; Clinical Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai

David C Ritterband, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, American College of Surgeons, International Society of Refractive Surgery

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.


Kerry Assil, MD Medical Director and CEO, The Sinskey Eye Institute

Kerry Assil, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, Association for Research in Vision and Ophthalmology, and Contact Lens Association of Ophthalmologists

Disclosure: Nothing to disclose.

Kilbourn Gordon III, MD, FACEP Urgent Care Physician

Kilbourn Gordon III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology and Wilderness Medical Society

Disclosure: Nothing to disclose.

Robert H Graham, MD Consultant, Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona

Robert H Graham, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Arizona Ophthalmological Society

Disclosure: Medscape/WebMD Salary Employment

Anisha Judge, MD Consulting Staff, Department of Ophthalmology, Kaiser Permanente at West Los Angeles Medical Center

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, and International Society of Refractive Surgery

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; Bausch & Lomb Honoraria Speaking and teaching; Merck Consulting fee Consulting; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jack L Wilson, PhD Distinguished Professor, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center College of Medicine

Jack L Wilson, PhD is a member of the following medical societies: American Association of Anatomists, American Association of Clinical Anatomists, and American Heart Association

Disclosure: Nothing to disclose.

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Herpes simplex virus dendritic ulcer stained with rose bengal.
Herpes simplex virus dendritic ulcer stained with fluorescein.
Large paracentral herpes simplex virus dendritic ulcer.
Recurrent herpes simplex virus dendritic ulcer with an adjacent stromal scar.
Healing herpes simplex virus dendritic ulcer.
Herpes simplex virus geographic ulcer.
Neurotrophic keratopathy.
Large neurotrophic ulcer.
Active immune stromal keratitis.
Inactive immune stromal keratitis.
Disciform endotheliitis with secondary stromal ulceration.
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