Ophthalmological Side Effects of Acyclovir
Acyclovir is generally well-tolerated ophthalmologically, with the most common ocular side effects being superficial punctate keratopathy (occurring in approximately 10% of patients) and mild burning or stinging upon application of topical formulations (4% of patients). 1, 2
Topical Acyclovir Ophthalmic Ointment
Common Adverse Effects
- Superficial punctate keratopathy occurs in 9.8% of patients treated with topical acyclovir ophthalmic ointment 2
- Burning or stinging sensation upon application affects 4% of patients 2
- Conjunctivitis, inflammation, and ocular pain have been reported in post-marketing surveillance, though these remain rare with approximately 43 spontaneous reports among an estimated one million exposures 2
Comparative Safety Profile
- Acyclovir demonstrates favorable tolerability compared to older antiviral agents like idoxuridine (IDU) and trifluridine 2, 3
- Unlike trifluridine, which causes epithelial toxicity when used for more than 2 weeks, topical acyclovir (and ganciclovir) are less toxic to the ocular surface 4
- Prolonged use of older antivirals can cause irreversible complications including conjunctival cicatrization, symblepharon, and permanent punctal occlusion—complications not typically associated with acyclovir 3
Systemic Acyclovir (Oral/Intravenous)
Ocular Manifestations from Systemic Administration
The FDA label and clinical guidelines identify visual abnormalities as a recognized adverse effect of systemic acyclovir, though specific details are limited 1
Neurological Side Effects with Ocular Implications
Systemic acyclovir can cause neurological adverse effects that may present with visual symptoms, particularly in high-risk populations 1:
- Confusion, hallucinations, and encephalopathy
- Decreased consciousness and delirium
- These symptoms are particularly marked in older adults and patients with renal impairment 1
Non-Ocular Side Effects Relevant to Ophthalmologic Practice
When prescribing acyclovir for ocular herpes infections, monitor for 5, 1:
- Renal impairment (crystalluria and obstructive nephropathy affecting up to 20% of patients on IV therapy, typically manifesting after 4 days) 5
- Hepatitis and bone marrow failure (rare) 5
- Hematologic effects including anemia, leukopenia, and thrombocytopenia 1
Clinical Context and Therapeutic Benefits
Risk-Benefit Considerations
Despite these potential side effects, acyclovir represents a major therapeutic advance with significant clinical benefits that far outweigh its risks 6, 7:
- Oral acyclovir reduces the incidence of ocular complications in herpes zoster ophthalmicus, including keratitis and uveitis 7
- Treatment initiated even as late as 7 days after onset confers beneficial prophylactic effects against ocular complications 7
- Acyclovir is effective for HSV corneal disease including dendritic ulcers, geographic ulcers, and deep corneal infections 2, 6
Important Clinical Caveats
- Topical corticosteroids should be avoided in HSV epithelial infections as they potentiate viral replication, though they may be used with concurrent oral antiviral therapy for HSV stromal keratitis 4
- Dose adjustment is essential in patients with renal impairment to prevent nephrotoxicity and neurological complications 5, 1
- Maintain adequate hydration during IV acyclovir therapy to reduce crystalluria risk 5
Monitoring Recommendations
For patients on systemic acyclovir therapy 5:
- Monitor renal function (BUN, creatinine) twice weekly during induction therapy, then weekly
- Assess for neurological symptoms, especially in elderly or renally impaired patients
- Ophthalmologic follow-up within 1 week of initiating treatment for HSV ocular disease 4