Author: Claude (AI), from PubMed abstracts · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Herpes simplex keratitis

Herpes simplex keratitis (HSK) is a common, potentially blinding condition characterised by recurrent corneal infection [S4] [S12]. An estimated 1.7 million people had HSV keratitis in 2016, and about 230,000 may have newly acquired uniocular vision impairment from it [S8]. Treatment aims to suppress viral replication, control immune-mediated stromal inflammation and protect the ocular surface [S12].

Key points - Epithelial keratitis: topical acyclovir and trifluridine are similarly effective and better than older antivirals; ganciclovir is at least as effective as acyclovir; oral acyclovir appeared as effective as a single topical antiviral [S2]. - Stromal keratitis: corticosteroids work best only when combined with antivirals [S9] [S10]. - After keratoplasty for HSK, oral acyclovir may reduce recurrence and graft failure (low-certainty evidence) [S3]. - Refractory disease needs reassessment of adherence, dosing and diagnosis, including acyclovir resistance [S11] [S12]. - Children have a more aggressive course with risk of scarring and amblyopia [S6].

Evidence last checked: 2026-10-17 (PubMed abstracts).

Red flags

• Steroid drops without antiviral cover. Corticosteroids and antivirals were effective mainly when used together [S9] [S10].
• A child with HSK. Disease is often more aggressive, with scarring and amblyopia [S6].
• No improvement despite appropriate treatment. Consider poor adherence, inadequate dosing, acyclovir resistance [S12] or cytomegalovirus [S11].
• Reduced corneal sensation or a non-healing defect. Recurrent inflammation can reduce corneal sensation and cause scarring [S4]; neurotrophic keratopathy is a driver of refractory disease [S12].
• Immunocompromised or long-term treated patients, in whom acyclovir-resistant strains are an increasing concern [S12].

Recognise it

• Burden. Pooled incidence of HSV keratitis was 24.0 per 100,000 person-years, mostly epithelial (16.1 per 100,000) [S8]. Data come only from the USA and Europe, and burden elsewhere is likely underestimated [S8].
• Course. HSV establishes latency in sensory ganglia, most often the trigeminal ganglion, and reactivates to cause recurrent corneal disease [S4].
• Forms. Epithelial keratitis, which is usually self-limiting but may persist or progress without treatment [S2], and stromal keratitis, an immune-mediated inflammation [S9] that is a leading cause of corneal opacification [S1].

Confirm it

• Diagnosis is usually clinical at the slit lamp, but clinical findings are not always accurate [S4].
• PCR, ELISA, immunofluorescence and viral culture give more definitive diagnosis, each with limitations [S4] [S11]. Laboratory options and their relative advantages are reviewed in [S12].

Manage it

Before acting on this section, check the national and local guidelines, product information and regulatory approvals that apply where you practise. See the medical disclaimer.

Tier A (primary care / no specialist)

• Do not prescribe steroid drops for a red eye with a suspected corneal lesion; steroids are useful in HSK only alongside antivirals [S9] [S10].
• Refer suspected HSK to an eye clinic (see "Refer when").

Tier B (general eye clinic)

Epithelial keratitis - A Cochrane review of 137 studies (8333 eyes) found trifluridine and acyclovir more effective than idoxuridine or vidarabine and similar to each other; ganciclovir is at least as effective as acyclovir [S2]. - In a limited number of studies, oral acyclovir alone (RR 0.92, 95% CI 0.79 to 1.07) appeared as effective as a single topical antiviral [S2], which may help where topical antivirals are unavailable. - Debridement or interferon added to an antiviral had inconsistent effects [S2].

Stromal keratitis - In a systematic review of 7 papers, prednisolone phosphate plus acyclovir gave higher success and longer time to failure than acyclovir alone [S9]. Oral and topical acyclovir did not differ in time to resolution [S9]. - Corticosteroids may give greater benefit when tapered and given for at least 10 weeks [S9]. Randomised trials support their safety and effectiveness with appropriate antiviral therapy [S10]. - Dosing is not covered by these abstracts: follow local formularies.

Tier C (specialist centre)

• Steroid-sparing agents. Cyclosporine A, tacrolimus and flurbiprofen may be safe and effective, on limited evidence [S9]; high-quality trials beyond steroids and antivirals are lacking [S1].
• Refractory and resistant disease. Options include higher acyclovir doses, oral valacyclovir, and topical foscarnet, ganciclovir, trifluridine or cidofovir [S11]; trifluridine, foscarnet and helicase-primase inhibitors such as amenamevir have shown efficacy [S12]. These come from narrative reviews.
• Neurotrophic component. Growth factor therapy, autologous serum, recombinant nerve growth factor or scleral lenses may help [S12].
• Keratoplasty for scarring. Penetrating keratoplasty and DALK gave comparable visual improvement, with fewer complications after DALK in most of 12 studies [S7]. Higher graft survival was associated with acyclovir above 800 mg/day, topical steroids and antibiotics, as reported in [S7].
• Prophylaxis after grafting. A Cochrane review of 3 trials (126 participants) found oral acyclovir for 6 months or more may reduce recurrence (RR 0.29, 95% CI 0.13 to 0.64) and graft failure (RR 0.40, 95% CI 0.16 to 0.97), about 23 fewer recurrences per 100 grafts; evidence was low certainty [S3].

Refer when

Pitfalls

• Using steroids alone [S9] [S10].
• Over-relying on the clinical picture; slit-lamp diagnosis is not always accurate [S4].
• Labelling every non-responder as resistant without checking adherence and dosing [S12] or cytomegalovirus [S11].
• Forgetting antiviral prophylaxis after keratoplasty [S3] [S7].

Evidence notes

• The Herpetic Eye Disease Study trials are not on this PubMed sheet and are not cited directly; stromal keratitis evidence here comes from a qualitative systematic review of 7 papers [S9] and narrative reviews.
• The trials in the graft prophylaxis review were poorly reported and none followed patients beyond two years [S3].
• Placebo-controlled epithelial trials are limited to superseded drugs; the ganciclovir advantage was mitigated by heterogeneity and possible publication bias [S2].
• Incidence data are from the USA and Europe only [S8].
• Main epithelial agents remain trifluridine drops, acyclovir ointment, ganciclovir gel and oral acyclovir [S5].
• Not covered by these sources: dose and duration of long-term suppressive therapy outside grafts, and management of HSV endotheliitis.

Related articles

• Herpes zoster ophthalmicus
• Neurotrophic keratopathy
• Topical and periocular corticosteroids: benefits and risks

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.