Herpes Simplex keratitis

Summary of Evidence

Herpes simplex keratitis

For patients with HSV epithelial keratitis treated with topical trifluridine, there was no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis in the subsequent year.(HEDS-EKT, 1997){A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1997 Jun;115(6):703-12.}

Stromal keratitis

Topical corticosteroids reduced persistence or progression of stromal inflammation and shortened the duration of herpes simplex stromal keratitis compared to placebo.(HEDS-SKN, 1994) {Wilhelmus KR, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Barron BA, Kaufman HE, Sugar J, Hyndiuk RA, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1883-95; discussion 1895-6.}

Iridocyclitis

There was a trend suggesting a benefit of oral acyclovir in the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.(HEDS-IRT, 1996) {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.}

Prophylaxis

After the resolution of ocular HSV disease, acyclovir (12-month course) reduces the rate of recurrent ocular HSV disease and orofacial HSV disease.(HEDS-APT, 1998) {Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6.}

Evidence

1. Risk factors

1.1 Potential triggers

Cohort study

2000 HEDS study group

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2000
Cohort study

No association was found between psychological stress, systemic infection, sunlight exposure, menstrual period, contact lens wear, and eye injury and an increased risk of recurrence of ocular herpes simplex virus. {Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000 Dec;118(12):1617-25.}

2. Epithelial Keratitis

2.1 Antiviral therapy

Review

2015 Wilhelmus (Cochrane review)

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2015
Review

Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.

Wilhelmus (Cochrane review)
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Review

2007 Guess et.al.

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2007
Review

Analysis of 30 studies for HSV epithelial keratitis: evidence supports the use of topical trifluridine and topical or oral acyclovir, and suggests a possible additional benefit for topical interferon. {Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007 Jul;5(3):240-50.}

Clinical Trial

1997 HEDS study group (HEDS-EKT)

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1997
Clinical Trial

For patients with HSV epithelial keratitis treated with topical trifluridine, there was no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis in the subsequent year. {A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1997 Jun;115(6):703-12.}

Randomized controlled trial of oral acyclovir vs placebo in patients with HSV epithelial keratitis and treated with trifluridine therapy (287 patients)
Findings
- Stromal keratitis/iritis developed in 11% in the acyclovir group and 10% of patients in the placebo group

HEDS study group (HEDS-EKT)
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3. Stromal Keratitis

3.1 Antiviral therapy

Clinical Trial

1994 Barron et.al. (HEDS-SKS)

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1994
Clinical Trial

There was no significant benefit of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine. {Barron BA, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Wilhelmus KR, Kaufman HE, Sugar J, Hyndiuk RA, et al. Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1871-82.}

Randomized controlled trial of oral acyclovir vs placebo in patients with HSV stromal keratitis and treated with Topical prednisolone phosphate and trifluridine (104 patients)
Findings
- At 16 weeks, treatment failure was 75% in the acyclovir group and 74% in the placebo group

Barron et.al. (HEDS-SKS)
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3.2 Adjunctive topical corticosteroids

Review

2007 Guess et.al.

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2007
Review

Analysis of 8 studies for HSV stromal keratitis: evidence supports the use of topical corticosteroids given with a prophylactic antiviral to shorten the duration of active HSV stromal keratitis. {Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007 Jul;5(3):240-50.}

Clinical Trial

1994 Wilhelmus et.al. (HEDS-SKN)

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1994
Clinical Trial

Topical corticosteroids reduced persistence or progression of stromal inflammation and shortened the duration of herpes simplex stromal keratitis compared to placebo. {Wilhelmus KR, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, Barron BA, Kaufman HE, Sugar J, Hyndiuk RA, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec;101(12):1883-95; discussion 1895-6.}

Randomized controlled trial of topical prednisolone phosphate vs placebo in patients with active HSV stromal keratitis and treated with topical trifluridine (106 patients).
Findings
- The time to treatment failure was significantly longer in the steroid group compared with the placebo group
- Corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%

Wilhelmus et.al. (HEDS-SKN)
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4. Iridocyclitis

4.1 Antiviral therapy

Clinical Trial

1996 HEDS study group (HEDS-IRT)

Article link | Archive link

1996
Clinical Trial

There was a trend suggesting a benefit of oral acyclovir in the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis. {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.}

Randomized controlled trial of oral acyclovir vs placebo in patients with HSV iridocyclitis and treated with topical prednisolone phosphate and trifluridine (50 patients)
Findings
- At 16 weeks, a treatment failure occurred in 50% in the acyclovir-treated group and 68% in the placebo group

HEDS study group (HEDS-IRT)
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5. Prophylaxis

5.1 Antiviral therapy

Review

2016 Bhatt et.al. (Cochrane review)

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2016
Review

Analysis of 3 trials involving 126 patients. Conclusion: “Oral antiviral (acyclovir) may reduce the risk of recurrence of herpetic keratitis in the first 12 months in eyes that have undergone corneal graft surgery.” {Bhatt UK, Abdul Karim MN, Prydal JI, Maharajan SV, Fares U. Oral antivirals for preventing recurrent herpes simplex keratitis in people with corneal grafts. Cochrane Database Syst Rev. 2016 Nov 30;11(11):CD007824.}

Bhatt et.al. (Cochrane review)
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Review

2007 Miserocchi et.al.

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2007
Review

One-year suppression therapy with oral valacyclovir was shown to be as effective and as well tolerated as acyclovir in reducing the rate of recurrent ocular HSV disease in a randomized controlled trial of 52 immunocompetent patients with a history of recurrent ocular HSV disease. {Miserocchi E, Modorati G, Galli L, Rama P. Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. Am J Ophthalmol. 2007 Oct;144(4):547-51.}

Review

2007 Guess et.al.

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2007
Review

Analysis of 8 studies for HSV stromal keratitis: evidence supports the use of long-term suppressive oral acyclovir therapy to reduce the incidence of recurrent HSV keratitis {Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007 Jul;5(3):240-50.}

Clinical Trial

1998 Wilhelmus et.al. (HEDS-APT)

Article link | Archive link

1998
Clinical Trial

After the resolution of ocular HSV disease, acyclovir (12-month course) reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. {Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6.}

Randomized controlled trial of oral acyclovir vs placebo in Immunocompetent patients who had ocular HSV in the preceding year (703 patients).
Findings
- At 12 months. recurrence of any type of ocular HSV disease was 19 percent in the acyclovir group and 32 percent in the placebo group.
- Higher recurrence of stromal keratitis in placebo group
- Higher recurrence of nonocular (primarily orofacial) in placebo group

Wilhelmus et.al. (HEDS-APT)
Journal full text Archive

6. Neonatal Herpes

6.1 Antiviral therapy

Clinical Trial

2011 Kimberlin et.al.

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2011
Clinical Trial

Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes at 12 months when they received suppressive therapy with oral acyclovir vs placebo for 6 months. {Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sánchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, McCarthy CA, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med. 2011 Oct 6;365(14):1284-92.}

Randomized controlled trial of immediate acyclovir suppression vs placebo in neonates with HSV following completion of 14-21 day regimen of parenteral acyclovir.
Findings
- At 12 months, infants with CNS involvement administered acyclovir suppression had significantly higher mean Bayley mental-development scores than did infants assigned to placebo.
- There was a trend toward more neutropenia in the acyclovir group than in the placebo group

References

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Herpes Simplex keratitis

Summary of Evidence

Evidence

1. Risk factors

1.1 Potential triggers

2. Epithelial Keratitis

2.1 Antiviral therapy

Details

3. Stromal Keratitis

3.1 Antiviral therapy

Details

3.2 Adjunctive topical corticosteroids

Details

4. Iridocyclitis

4.1 Antiviral therapy

Details

5. Prophylaxis

5.1 Antiviral therapy

Details

6. Neonatal Herpes

6.1 Antiviral therapy

Details

References

Comments