Ophthalmic Antivirals

Concise summaries of ophthalmic antiviral agents used in eye care practice in Singapore, including clinical pharmacology, dosing, patient selection, Singapore regulatory status, and guidance on when to refer urgently.

Last updated: March 2026

What are ophthalmic antivirals?

Ophthalmic antiviral agents are topical pharmaceutical preparations applied directly to the ocular surface to treat viral infections of the eye — principally herpes simplex virus (HSV) keratitis. They work by selectively inhibiting viral DNA replication, exploiting enzymes that are expressed specifically in virus-infected cells, thereby minimising toxicity to uninfected host tissue.

In Singapore, HSV-1 is the predominant pathogen causing ocular disease, with herpes simplex keratitis being the leading infectious cause of corneal blindness and corneal transplantation worldwide. Herpes zoster ophthalmicus (HZO), caused by reactivation of varicella-zoster virus (VZV), is also clinically significant — particularly in older patients and in the context of Singapore's ageing population and high immunocompromised cohort following organ transplantation at SNEC, NUH, and SGH.^[1,2]

Drug classes

Nucleoside analogues — acyclovir-class (HSV-selective): Acyclovir (Zovirax) is phosphorylated exclusively by HSV thymidine kinase, conferring high selectivity for infected cells. Valacyclovir (oral prodrug) is used systemically for HSV prophylaxis and HZO.
Nucleoside analogues — broader spectrum (HSV + CMV): Ganciclovir (Virgan 0.15% gel) is activated by both HSV thymidine kinase and CMV UL97 kinase, providing activity against HSV-1, HSV-2, and CMV. Used topically for HSV keratitis and in specialist management of CMV keratitis.
Thymidine analogues — second-line: Trifluridine 1% is a halogenated thymidine analogue with broader antiviral spectrum but greater epithelial toxicity; reserved for acyclovir-resistant cases and used only in hospital formularies (SNEC, NUH, TTSH).
Systemic antivirals (for reference): Oral acyclovir and valacyclovir are prescribed by medical practitioners for HZO, recurrent HSV, and suppressive therapy. They fall outside the topical ophthalmic scope but are fundamental to the co-management of viral eye disease.

Who are they for?

Ophthalmic antivirals are indicated for patients with active viral infections of the anterior ocular surface — primarily HSV epithelial keratitis. In Singapore, optometrists regularly encounter patients presenting with acute red eye, photophobia, and reduced vision who may have viral corneal disease requiring urgent medical referral. Recognition of the clinical pattern is essential: optometrists do not prescribe antivirals, but they are often the first point of contact and play a critical triage role.^[3]

Patient profiles and common conditions

HSV epithelial keratitis

Dendritic or geographic corneal ulcers — hallmark of primary or recurrent HSV-1 infection. Presents with reduced vision, pain, photophobia, and characteristic branching fluorescein staining. Topical antivirals are first-line; refer to ophthalmologist.

HSV stromal keratitis

Immune-mediated deep stromal opacity, neovascularisation, or endotheliitis. Requires specialist co-management with topical steroids under antiviral cover. Not suitable for community management — refer urgently to ophthalmologist.

Herpes zoster ophthalmicus (HZO)

VZV reactivation in the ophthalmic division of CN V — periocular dermatomal rash, Hutchinson's sign. Ocular complications in 50–72% if untreated. Requires urgent systemic antiviral (oral valacyclovir/acyclovir) within 72 h of rash onset; refer immediately.

CMV keratitis / anterior uveitis

Predominantly in immunocompromised patients (post-transplant on tacrolimus, HIV). Presents as coin-shaped endothelial lesions with raised IOP. Ganciclovir gel or systemic valganciclovir under specialist supervision only; always refer.

Caution — contact lens wearers

Contact lens wear must be ceased immediately in any patient with suspected viral keratitis. Continued lens wear risks mechanical inoculation of adjacent corneal tissue, secondary bacterial superinfection, and delayed healing. Advise complete cessation of all lens wear until the episode has fully resolved and the patient has been reviewed and cleared by an ophthalmologist. Do not refit until corneal integrity is confirmed.

When should they be used?

Acute epithelial HSV keratitis

Topical acyclovir 3% ointment (Zovirax) or ganciclovir 0.15% gel (Virgan) should be initiated as early as possible once diagnosis is confirmed by an ophthalmologist. Typical course is 14 days, with clinical review at 7 days. Healing of epithelial dendrites is expected within 7–10 days with adequate treatment. Topical antivirals are not indicated for stromal or endothelial disease without specialist co-prescribing of topical steroids.

Prophylactic / suppressive therapy

Oral valacyclovir 500 mg OD (or acyclovir 400 mg BD) is prescribed by medical practitioners for long-term suppressive therapy in patients with frequent HSV recurrences (≥2 episodes/year) or after penetrating keratoplasty (PK) for herpetic disease. The Herpetic Eye Disease Study (HEDS) demonstrated a 45% reduction in stromal keratitis recurrence with oral acyclovir prophylaxis.^[4]Topical antivirals are not used for long-term prophylaxis.

Escalation and urgent referral

Any patient with stromal involvement, severe corneal thinning, perforation risk, HZO, or CMV keratitis must be referred to an ophthalmologist — ideally the same day. SNEC and NUH Eye Institute offer emergency eye clinics for these presentations. Do not delay referral to initiate topical treatment: the potential for irreversible corneal scarring and visual loss is high.

Clinical presentation	Recommended action	Urgency
Dendritic/geographic epithelial HSV keratitis	Topical acyclovir or ganciclovir; cease CL wear	Refer to ophthalmologist; same-day preferred
HSV stromal keratitis (opacity, neovascularisation)	Topical antiviral + steroid under specialist supervision	Urgent referral — same day
HZO (periocular rash ± Hutchinson's sign)	Systemic valacyclovir/acyclovir within 72 h of rash	Urgent referral — same day; call ahead to ophthalmology
CMV keratitis / endotheliitis (immunocompromised)	Ganciclovir gel or systemic valganciclovir — specialist only	Urgent referral — same day to cornea/uveitis specialist

Where are they available in Singapore?

In Singapore, all ophthalmic antiviral agents are regulated by the Health Sciences Authority (HSA) under the Medicines Act as Prescription-Only Medicines (POM). No ophthalmic antiviral is available OTC or as a Pharmacy medicine. Current product registration status should always be verified via the HSA product registration portal before recommending or referring for any specific agent.

Scope of practice — Singapore optometrists

Under the Optometrists and Opticians Act (Cap. 213A) and governed by the Optometrists and Opticians Board (OOB), Singapore-registered optometrists are authorised to examine eyes and prescribe optical appliances. They do not hold therapeutic prescribing rights and cannot prescribe, supply, or administer antiviral medications — including topical acyclovir or ganciclovir eye preparations — under any circumstances. All patients with suspected viral keratitis or HZO must be referred promptly to a registered medical practitioner, typically an ophthalmologist.^[5,6]

Prescription-Only (POM): Acyclovir 3% ointment (Zovirax Eye Ointment) and ganciclovir 0.15% gel (Virgan) are both POM — available only on a prescription from a registered medical practitioner. They are dispensed at hospital pharmacies and some private specialist outpatient pharmacies.
Hospital formularies: SNEC, NUH Eye Institute, and TTSH ophthalmology formularies stock acyclovir ointment and ganciclovir gel; trifluridine 1% drops are available only at selected tertiary centres for resistant or refractory cases.
Private ophthalmology clinics: Many specialist eye clinics dispense acyclovir ointment and ganciclovir gel in-house; systemic antivirals (oral valacyclovir) are prescribed by both GPs and ophthalmologists and dispensed at retail pharmacies.
Community pharmacies: Ophthalmic antivirals are not stocked at Guardian, Watsons, or Unity without a prescription. Oral acyclovir and valacyclovir (systemic) require prescription and may be dispensed at retail pharmacies.
HSA product verification: Registration status and supply schedule for all antiviral products can be confirmed via the HSA product registration portal (hsa.gov.sg). Always verify current registration before recommending any specific product.^[5]

Why use topical ophthalmic antivirals over systemic agents?

Topical ophthalmic antivirals deliver high local drug concentrations directly to the infected corneal epithelium, achieving therapeutic levels that would require prohibitively high systemic doses to replicate — and without the systemic adverse-effect burden. For superficial epithelial HSV keratitis, topical therapy is the treatment of choice.

Targeted epithelial penetration

High local concentrations at the corneal epithelium — the primary site of HSV viral replication — without systemic peak levels or renal load.

Reduced systemic toxicity

Avoids the nephrotoxicity, nausea, and headache associated with systemic acyclovir at doses required for corneal tissue penetration via the bloodstream.

Selective viral inhibition

Acyclovir and ganciclovir are phosphorylated preferentially by viral kinases in infected cells, minimising toxicity to surrounding healthy epithelial cells.

When systemic agents are mandated

Stromal keratitis, HZO, and CMV disease require systemic antivirals (oral valacyclovir or acyclovir) because topical preparations cannot penetrate to the stroma or uveal tract at therapeutic concentrations.

For stromal or endothelial HSV keratitis, topical antivirals alone are insufficient — systemic oral acyclovir or valacyclovir is required to achieve therapeutic stromal concentrations. These cases must be co-managed by an ophthalmologist, who will also determine whether adjunctive topical steroids are appropriate under antiviral cover.^[4,7]

How to use ophthalmic antivirals — patient instructions

Instillation technique

Wash hands thoroughly before and after handling the preparation — HSV is transmissible via contact.
Tilt head back slightly and gently pull down the lower eyelid to form a small pocket (lower fornix).
For ointment: squeeze approximately 1 cm ribbon into the lower fornix without touching the tip to the eye, eyelid, or any surface. For gel drops: instil one drop into the lower fornix.
Gently close the eye and apply gentle nasolacrimal occlusion (press the inner corner of the eye with one finger) for 1–2 minutes to improve local contact time and reduce drainage.
If using more than one eye preparation, wait at least 5 minutes between each. Instil drops before ointment or gel if both are prescribed.
Recap and store the preparation correctly; do not share with others — viral ocular infections can be transmitted via contaminated bottles or applicator tips.

Contact lens guidance

Cease all contact lens wear immediately at presentation of suspected viral keratitis — do not reinsert until formally cleared by an ophthalmologist.
Discard the current pair of lenses and lens case — they may be contaminated. Do not reuse any lens that was worn during the active episode.
Ointment and gel formulations are incompatible with contact lens wear — the lipid base of ointments deposits onto soft lenses and cannot be removed by standard disinfection.
Following full resolution, discuss long-term lens hygiene, replacement frequency, and the elevated recurrence risk associated with lens-related corneal microtrauma before refitting.

Monitoring and red-flag referral

All patients: Clinical review at 7 days — the dendritic ulcer should be resolving or healed. Failure to improve within 7 days warrants urgent reassessment for resistant virus, secondary bacterial infection, or stromal involvement.
Red flag — refer immediately: Worsening pain or photophobia, reduced visual acuity, corneal thinning or melting, hypopyon, significant anterior chamber reaction, or periocular vesicular rash (HZO pattern).
Steroid co-prescription: If an ophthalmologist has co-prescribed topical steroids with antiviral cover, monitor IOP at every visit — steroids accelerate viral replication if antiviral cover lapses.
Immunocompromised patients: Higher risk of atypical presentation, treatment resistance, and bilateral disease; lower threshold for same-day specialist referral and systemic antiviral therapy.
Recurrent disease: Counsel on triggers (UV exposure, febrile illness, psychological stress, immunosuppression) and the benefit of long-term oral antiviral suppression — to be initiated by the managing ophthalmologist.

Common ophthalmic antivirals in Singapore

All agents listed are, or have been, registered with HSA Singapore or are available through registered importers / hospital formularies. Verify current product registration at hsa.gov.sg before prescribing or referring.

Brand (Generic)	Mechanism / Class	Dosing	Min. Age	Side Effects & Precautions	Clinical Notes
Zovirax Eye Ointment Acyclovir 3% ophthalmic ointment POM	Nucleoside analogue — selectively inhibits HSV-1 and HSV-2 DNA polymerase	1 cm ribbon 5× daily; continue 3 days after healing	≥2 years	Stinging, punctate keratopathy, hypersensitivity (rare)	First-line for HSV epithelial keratitis; refer immediately for stromal involvement
Virgan Ganciclovir 0.15% ophthalmic gel POM	Nucleoside analogue — inhibits HSV + CMV DNA polymerase; broader spectrum than acyclovir	1 drop 5× daily until healed, then TID for 7 days	≥2 years	Transient blurred vision, stinging, punctate keratitis	Alternative to acyclovir; consider if acyclovir resistance suspected
Trifluridine 1% Trifluridine 1% ophthalmic solution POM	Thymidine analogue — inhibits viral DNA synthesis; broader spectrum than acyclovir	1 drop every 2 h (max 9×/day); taper to every 4 h for 7 days	≥6 years	Punctate keratopathy, stromal oedema, hypersensitivity; epitheliotoxic	Hospital formulary only; reserved for acyclovir-resistant HSV keratitis

Legend

POMPrescription Only Medicine — Sold or supplied to the public on prescription only.

PPharmacy Medicine — Sold or supplied from any licensed retail pharmacy under pharmacist supervision.

OTCGeneral Sales List (GSL) — Sold or supplied to the public without restriction.

Dosing reflects standard adult doses unless noted. Always refer to the approved product insert for full prescribing information. OD = once daily, BD = twice daily, TID = three times daily, QID = four times daily, PRN = as needed.

References

[1] Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol. 2012;57(5):448–462. PMID: 22542912.
[2] Young AL, Leung KS, Cheng LL, et al. Herpes zoster ophthalmicus in Singapore. Eye (Lond). 2004;18(12):1221–1226. PMID: 15002005.
[3] George PP, Chng OSY, Siow K, et al. Is there scope for expanding the optometrist's scope of practice in Singapore? A survey of optometrists and opticians. Cont Lens Anterior Eye. 2019;42(3):258–264. PMID: 30819628.
[4] 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. PMID: 9682040.
[5] Republic of Singapore. Optometrists and Opticians Act 2007 (No. 16 of 2007). Singapore Statutes Online. Available at: sso.agc.gov.sg/Act/OOA2007 (accessed March 2026).
[6] Health Sciences Authority Singapore. Medicines Act (Cap. 176). HSA. Available at: hsa.gov.sg (accessed March 2026).
[7] Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;(1):CD002898. PMID: 25879115.
[8] Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007;5(3):240–250. PMID: 17660897.
[9] Tabbara KF, Al-Balawi SA. Ganciclovir ophthalmic gel 0.15% versus acyclovir ophthalmic ointment 3% in patients with herpes simplex keratitis. Acta Ophthalmol. 2012;90(7):e534–e540. PMID: 22978800.
[10] Chong EM, Wilhelmus KR, Matoba AY, et al. Herpes simplex virus keratitis in children. Am J Ophthalmol. 2004;138(3):474–475. PMID: 15364233.

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