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Herpetic Eye Disease Study (HEDS) I

Also see Herpetic Eye Disease Study II.

Purpose | Background | Description | Patient Eligibility | Recruitment Status | Current Status | Results | Publications | Resource Centers | NEI Representative

Purpose

Background

Herpes simplex keratitis is a leading cause of corneal opacification in the United States, other industrialized countries, and developing nations throughout the world. An estimated 450,000 people in the United States can develop recurrent episodes of the disease and about 46,000 episodes of HSV eye infection every year. Herpetic eye disease is the most common infectious cause of corneal blindness in this country.

Despite the availability of antiviral agents that are effective in treating herpes simplex epithelial keratitis, inflammation in the corneal connective tissue and iris that can lead to corneal scarring and visual impairment develops in many patients. Prior to the HEDS-I trials, the role of topical corticosteroids in the management of HSV stromal keratitis was uncertain; some animal and human studies suggested there was a benefit to treatment whereas others suggested harm. The value of adding an oral antiviral agent to treatment with topical corticosteroids and topical antivirals also was unknown.

The HEDS-I trials were developed to assess the efficacy of topical corticosteroids and oral acyclovir in treating HSV stromal keratitis and iridocyclitis.

Description

HEDS-I consisted of three randomized, placebo-controlled trials. The organizational structure consisted of a data coordinating center and eight clinical centers.

All patients received the topical antiviral trifluridine as prophylaxis against recurrences of HSV epithelial ulceration. Patients were evaluated weekly for 10 weeks, every other week through week 16, and again at 6 months. The primary outcome was the time to development of preset criteria for treatment failure during the 16-week period of examination. Protocol-specific descriptions of the three trials follow.

Herpes Stromal Keratitis, Not on Steroid Trial (HEDS-SKN):
Patients with active HSV stromal keratitis who had not used a topical corticosteroid in the preceding 10 days were randomized to treatment with topical prednisolone phosphate drops or topical placebo drops. A treatment schedule, starting with 8 drops a day of 1 percent prednisolone phosphate for 7 days, was progressively decreased over 10 weeks in such a way that patients received 1 drop per day of 1/8 percent prednisolone for the last 3 weeks of treatment. Placebo drops were given by the same schedule.

Herpes Stromal Keratitis, on Steroid Treatment (HEDS-SKS):
Patients with active HSV stromal keratitis who already were being treated with a topical corticosteroid were randomized either to oral treatment with 200 mg acyclovir capsules (400 mg five times daily) for 10 weeks or to the identical dose of placebo capsules. Patients also received topical prednisolone phosphate in the dosage schedule described above for the SKN trial.

Herpes Simplex Virus Iridocyclitis, Receiving Topical Steroids (HEDS-IRT):
Patients with active HSV iridocyclitis were randomized either to oral treatment with 200 mg acyclovir capsules (400 mg five times daily) for 10 weeks or to the identical dose of placebo capsules. Patients also received topical prednisolone phosphate in the dosage schedule described above for the SKN trial.

Patient Eligibility

Eligibility criteria common to the three protocols included age 12 years or older, no active HSV epithelial keratitis, no prior keratoplasty of the involved eye, and not pregnant. Protocol-specific criteria are noted in the description above.

Patient Recruitment Status

Completed.

Current Status of Study

Completed.

Results

Herpes Stromal Keratitis, Not on Steroid Trial (HEDS-SKN):
Patient recruitment was stopped on the recommendation of the Data and Safety Monitoring Committee after 106 of the originally planned 176 patients were enrolled. Compared with the patients in the placebo group, the patients who received prednisolone phosphate drops had faster resolution of the stromal keratitis and fewer treatment failures. However, delaying the initiation of corticosteroid treatment did not affect the eventual outcome of the disease, in that visual acuity was similar in the two groups at 26 weeks.

Herpes Stromal Keratitis, on Steroid Treatment (HEDS-SKS):
One hundred and four patients were enrolled in this trial. Over the 16-week followup period, there was no difference in the rate of treatment failure between the two groups. Thus, there was no apparent benefit in the addition of oral acyclovir to the treatment regimen of a topical corticosteroid and a topical antiviral.

Herpes Simplex Virus Iridocyclitis, Receiving Topical Steroids (HEDS-IRT):
The trial was stopped because of slow recruitment after only 50 of the originally planned 104 patients were enrolled during a 4-year recruitment period. Treatment failures occurred at a higher rate in the placebo group than in the acyclovir group. Although the number of patients enrolled in this trial was too small to achieve statistically conclusive results, the trend in the results suggests a benefit in adding oral acyclovir to the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.

Publications

Herpetic Eye Disease Study Group: A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. Arch Ophthalmol 114: 1065-1072, 1996.

Wilhelmus KR, Dawson CR, Barron BA, Bacchetti P, Gee L, Jones DB, Kaufman HE, Sugar J, Hyndiuk RA, Laibson PR, Stulting RD, Asbell PA: Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis. Br J Ophthalmol 80: 969-972, 1996.

Barron BA, Gee L, Hauck WW, Herpetic Eye Disease Study: A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology 101: 1871-1882, 1994.

Wilhelmus KR, Gee L, Hauck WW, Herpetic Eye Disease Study: A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology 101: 1883-1896, 1994.

Dawson CR, Hauck WW, Jones DB, Kaufman HE, Gee L, Barron BA, Wilhelmus KR: The Herpetic Eye Disease Study (HEDS). Clinical characteristics of randomized patients with herpetic stromal keratitis and iridocyclitis prior to initiating treatment [Abstract]. Invest Ophthalmol Vis 33: 1134, 1992.

Dawson CR, Jones DB, Kaufman HE, Barron BA, Hauck WW, Wilhelmus KR: Design and organization of the Herpetic Eye Disease Study Group (HEDS). Curr Eye Res 10: 105-110, 1991.

Dawson CR, Jones DB, Wilhelmus KR, Kaufman HE, Barron BA, Hauck WW: Evaluation of corneal inflammatory disease: The Herpetic Eye Disease Study (HEDS) [Abstract]. Invest Ophthalmol Vis Sci 32: 1221, 1991.

Dawson CR: The Herpetic Eye Disease Study. Arch Ophthalmol 108: 191-192, 1990.

Dawson CR, Jones DB, Kaufman HE, Barron BA, Hauck WW, Wilhelmus KR: The Herpetic Eye Disease Study: Strategies of design and data analysis [Abstract]. Invest Ophthalmol Vis Sci 31: 553, 1990.

Resource Centers

Chairman's Office

Chandler R. Dawson, M.D.
Francis I. Proctor Foundation
University of California, San Francisco
95 Kirkham Street, Box 0944
San Francisco, CA 94143-0944
Telephone: (415) 476-2658
Fax: (415) 476-6085

Coordinating Center
Walter W. Hauck, Ph.D.
Francis I. Proctor Foundation
University of California, San Francisco
95 Kirkham Street, Box 0944
San Francisco, CA 94143-0944
Telephone: (215) 598-0753

Roy Beck, M.D., Ph.D.
Jaeb Center for Health Research, Inc.
3010 East 138th Avenue, Suite 9
Tampa, FL 32613
Telephone: (813) 975-8690

NEI Representative

Natalie Kurinij, Ph.D.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528

Last Updated: 10/21/99



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