Herpes simplex virus (HSV) is the most common infective cause of blindness in developed countries, with a reported incidence of 5.9 to 20.7 episodes per 100,000 persons each year.1

In 1992, the National Eye Institute (NEI) sponsored the Herpetic Eye Disease Study (HEDS) to improve the care and treatment of periocular infection. HEDS 1 investigated the benefit of adding topical steroids with topical trifluridine for the treatment of stromal keratitis. It also evaluated the efficacy of oral acyclovir in treating herpes simplex stromal keratitis in patients on concomitant topical corticosteroids and trifluridine, and the efficacy of adding oral acyclovir to a topical cortico-steroid and trifluridine for the treatment of iridocyclitis.2

HEDS II studied whether early oral acyclovir treatment of HSV corneal ulcerations prevented progression to the blinding complications of stromal keratitis and irido- cyclitis. It also studied the efficacy of low dose oral acyclovir in preventing recurrent infection and the role of external factors (such as life stress) on the induction of recurrent HSV eye infections and disease.3 The entire study ended in 1998.

Here, we will review the various forms of periocular infection and the treatment options available.

Periocular Infection
Periocular infection may present with only a periorbital dermatitis, but may also include blepharoconjunctivitis, epithelial keratitis, stromal keratitis and iridocyclitis.

The recurrence rate of ocular HSV is approximately 20% within two years, 40% within five years and 67% within seven years.4

Active epithelial keratitis. This appears as diffuse epithelial punctate keratopathy or corneal dendrites. The recommended treatment is Viroptic (trifluridine 1%, Monarch) ophthalmic solution every two hours, up to nine times per day. While not yet available in the U.S., ophthalmic acyclovir is available in Europe.

In a systematic review of clinical studies on the treatment of dendritic epithelial keratitis, the topical application of vidarabine, trifluridine or acyclovir generally resulted in a greater proportion of healing within one week of treatment, when compared with idoxuridine (an ophthalmic antiviral), though no treatment emerged as significantly better.5 However, topical acyclovir is not as toxic to the cornea as trifluridine.6

Taper treatment with topical antivirals according to the destruction of the lesion. Do not prescribe topical steroids in epithelium-only herpes cases. There will be minimal corneal inflammation, but there is a high risk for viral proliferation, as topical steroids enhance proliferation of HSV in epithelial disease.7

Stromal keratitis. This appears as single or multiple white patches of infiltration and inflammation within the corneal stroma. Concurrent stromal edema, stromal vascularization and secondary anterior uveitis accompany this.8

Use topical steroids to treat necrotizing and non-necrotizing stromal keratitis to reduce the amount of inflammation and scarring. If there is an overlying epithelial defect, add topical antivirals to treat the active virus until the epithelium heals. This method of treatment resulted from a HEDS 1 evaluation of the benefit of adding topical steroids and an oral antiviral to topical trifluridine for the treatment of stromal keratitis.2 These patients need careful monitoring and may require a referral to a corneal specialist. In HEDS 1, oral acyclovir showed no apparent benefit in the treatment of active stromal keratitis.2

Herpes simplex iridocyclitis. This is characterized by swelling of the iris and the surrounding area. Clinical findings commonly include granulomatous or nongranulomatous iridocyclitis and elevated intraocular pressure. We routinely use topical steroids and cycloplegics to treat iritis, with dosages depending on the severity. The combination of drops reduces the inflammatory response and ocular pain.

However, because iridocyclitis may be the result of an active viral infection, HEDS I (HEDS-IRT) evaluated the effectiveness of oral acyclovir in combination with topical corticosteroids and trifluridine treatment.2

Although this trial was prematurely stopped due to low participation, a trend suggested that oral acyclovir, when used in conjunction with topical corticosteroids and trifluridine prophylaxis, was beneficial.9 As a result, oral acyclovir (400mg five times a day) is also indicated for patients with herpes-related iridocyclitis.

Today, Famvir (famciclovir, Novartis) and Valtrex (valacyclovir,GlaxoSmithKline), prodrugs of acyclovir, are available and are viable treatment options. These are more readily absorbed by the body and have a longer half life, thus aiding in compliance.10

As primary-care providers, we must keep track of the latest research to spare patients from the physical and social pain that stems from HSV complications. 

1. Liesegang TJ, Melton LJ 3rd, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982. Arch Ophthalmol 1989 Aug;107(8):1155-9.
2. National Eye Institute. Clinical Studies Database: Herpetic Eye Disease Study (HEDS) 1.
www.nei.nih.gov/neitrials/viewStudyWeb.aspx?id=37 (23, July 2004).
3. National Eye Institute. Clinical Studies Database: Press Release Announcing Results. Herpetic Eye Disease Study (HEDS) II
www.nei.nih.gov/neitrials/viewStudyWeb.aspx?id=384. (23, July 2004)
4. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea 2001 Jan;20(1):1-13.
5. Wilhelmus KR. Interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev 2003;(3):CD002898.
6. Sowka J, Kabat, A. Corneal Atlas: How to fight back when infections attack. Rev Optom 1999 Aug 15;136(8):90-100.
7. Easty DL, Carter C. Mechanisms of resistance and hypersensitivity in herpes simplex keratitis. Trans Ophthalmol Soc U K 1979 Apr;99(1):126-33.
8. Sowka JW, Gurwood AS, Kabat AG. Immune stromal (interstitial) keratitis. Handbook of Ocular Disease Management. Rev Optom (suppl) 2004 March 15;141(3):27A-29A.
9. A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye Disease Study Group. Arch Ophthalmol 1996 Sep;114(9):1065-72.
10. Hoscheit, AM. Ocular HSV: treatment options: There are several viable options for treating a patient with herpetic eye disease. Rev Optom 2003; June 15 140(6): 81-2.

Vol. No: 141:08Issue: 8/15/04