What the evidence says
Why steroid drops wait for ophthalmology
68%lower risk of stromal inflammation persisting or worsening with prednisolone drops compared with placebo. Every patient was also on an antiviral drop, so the steroid was never given alone.Herpetic Eye Disease Study 1994, Ophthalmology, randomized trial, 106 patients
6 monthsafter randomization, vision was no different in patients whose steroid was held for a few weeks of close observation. The delay slowed healing, but a short wait for ophthalmology to start the steroid did not cost final vision.Herpetic Eye Disease Study 1994, Ophthalmology
3 in 4patients had failed treatment by 16 weeks even on steroid and antiviral drops, and adding oral acyclovir did not change that rate, although more patients on acyclovir gained vision by 6 months. Stromal keratitis is a long, relapsing course.Herpetic Eye Disease Study 1994, Ophthalmology, randomized trial, 104 patients
Strongrecommendation from the Academy to treat epithelial HSV keratitis with antivirals alone and avoid steroid drops. In an older cohort, geographic ulcers were more likely to have been treated with a steroid and took longer to heal.American Academy of Ophthalmology treatment guideline 2014; Wilhelmus 1981, Archives of Ophthalmology, cohort, 152 patients
Steroid drops help stromal HSV, but only paired with an antiviral, only after an ophthalmologist has ruled out active epithelial infection at the slit lamp, and over a taper of ten weeks or longer. The trial data say a short wait for that visit is safe. A steroid started on an unrecognized epithelial infection or a mimic is the situation the guideline warns against.
Why recurrence prevention matters
32% to 19%was the drop in any herpetic eye recurrence over a year of oral acyclovir 400 mg twice daily, with no rebound in the six months after it stopped.Herpetic Eye Disease Study 1998, New England Journal of Medicine, randomized trial, 703 patients
28% to 14%was the drop in stromal recurrence among the 337 patients who had already had stromal keratitis. A follow up analysis found the stromal benefit was limited to these patients.Herpetic Eye Disease Study 1998 and 2000, New England Journal of Medicine and Archives of Ophthalmology
10 timesthe risk of another stromal episode followed a prior episode of stromal keratitis, and the risk rose with each past episode. A past epithelial episode did not predict more epithelial disease.Herpetic Eye Disease Study 2001, Cornea, placebo arm of a randomized trial, 346 patients
40,000new cases of severe vision loss or blindness in one eye each year are estimated worldwide from HSV keratitis, among roughly 1.5 million cases. The authors call this a conservative estimate.Farooq 2012, Survey of Ophthalmology, epidemiologic review
Recurrences, not the first episode, are what scar corneas, and patients with prior stromal disease gain the most from suppression. The first clinician does not need to start prophylaxis, but putting the history of past herpetic eye episodes in the referral lets ophthalmology make the call quickly.
Antivirals and mimics
RR 0.92for healing with oral acyclovir compared with a topical antiviral drop (95% CI 0.79 to 1.07), in the limited trials that tested it. Using an oral and a topical antiviral together has not been shown to speed healing.Wilhelmus 2015, Cochrane Database of Systematic Reviews
77%of dendritic ulcers healed by day 7 with ganciclovir gel (Zirgan), compared with 72% with acyclovir ointment. The labeled course continues after day 7 when needed.Zirgan prescribing information, randomized trial, 164 patients
38%of Acanthamoeba keratitis cases at one referral center, and 37% at another, were first misdiagnosed as herpetic keratitis. Most patients wore contact lenses, and only 11% had the textbook ring infiltrate.Shah 2021, Acta Ophthalmologica, 43 patients; Höllhumer 2020, Eye, 52 patients
OR 3.9for a poor outcome in Acanthamoeba keratitis when a steroid drop was given before the correct diagnosis (95% CI 1.78 to 8.55), meaning vision 20/80 or worse, perforation, or transplant. The authors traced this mostly to the infection being mistaken for herpes.Robaei 2014, Ophthalmology, cohort, 196 patients
For epithelial HSV, one correctly dosed oral or topical antiviral is enough, and an oral agent can be started at the point of care when drops are not on hand. In a contact lens wearer, a dendrite like or slow healing keratitis should be treated as possible Acanthamoeba until ophthalmology has examined it, one more reason the steroid decision belongs to ophthalmology.
- Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101(12):1883-1896. doi:10.1016/s0161-6420(94)31087-6
- Barron BA, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology. 1994;101(12):1871-1882. doi:10.1016/s0161-6420(13)31155-5
- White ML, Chodosh J. Herpes simplex virus keratitis: a treatment guideline. American Academy of Ophthalmology; 2014. aao.org clinical statement Dosing on this page follows its Appendix VI.
- Wilhelmus KR, Coster DJ, Donovan HC, et al. Prognostic indicators of herpetic keratitis: analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol. 1981;99(9):1578-1582. doi:10.1001/archopht.1981.03930020452009
- Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998;339(5):300-306. doi:10.1056/NEJM199807303390503
- Herpetic Eye Disease Study Group. Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Arch Ophthalmol. 2000;118(8):1030-1036. doi:10.1001/archopht.118.8.1030
- Herpetic Eye Disease Study Group. Predictors of recurrent herpes simplex virus keratitis. Cornea. 2001;20(2):123-128. doi:10.1097/00003226-200103000-00001
- Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448-462. doi:10.1016/j.survophthal.2012.01.005
- Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;(1):CD002898. doi:10.1002/14651858.CD002898.pub5
- Zirgan (ganciclovir ophthalmic gel) 0.15%. Prescribing information. Bausch and Lomb; May 2026. DailyMed
- Shah YS, Stroh IG, Zafar S, et al. Delayed diagnoses of Acanthamoeba keratitis at a tertiary care medical centre. Acta Ophthalmol. 2021;99(8):916-921. doi:10.1111/aos.14792
- Höllhumer R, Keay L, Watson SL. Acanthamoeba keratitis in Australia: demographics, associated factors, presentation and outcomes: a 15-year case review. Eye (Lond). 2020;34(4):725-732. doi:10.1038/s41433-019-0589-6
- Robaei D, Carnt N, Minassian DC, et al. The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis. Ophthalmology. 2014;121(7):1383-1388. doi:10.1016/j.ophtha.2014.01.031
Written by Maddie Leung, BS. References pending author review. Draft for committee review.