Abstract
BACKGROUND: Human herpesvirus 7 (HHV-7), a β-herpesvirus with a known tropism for CD4⁺ T cells, has not been associated with ocular surface disease. To date, no definitive cases of corneal epithelial infection directly attributed to HHV-7 have been reported. This case highlights a unique corneal manifestation following ocular surgery and provides molecular evidence supporting HHV-7 as a primary pathogen. CASE PRESENTATION: A 32-year-old man with keratoconus underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Twelve days postoperatively, he developed a large geographic corneal epithelial ulcer with terminal bulbs which is classically seen in herpes simplex virus (HSV) keratitis, accompanied by conjunctival injection and ocular discomfort. Tear samples revealed HHV-7 DNA (1.1 × 10⁴ copies/sample) and U79 mRNA (1.3 × 10² copies) by quantitative polymerase chain reaction (PCR), with all other human herpesviruses testing negative. Treatment with oral valacyclovir (1000 mg TID) and topical 1% ganciclovir led to complete re-epithelialization within two weeks and a corresponding reduction in HHV-7 DNA and mRNA levels. Interestingly, multiple non-staining, grayish-white epithelial elevations resembling Thygeson’s superficial punctate keratitis emerged during recovery. HHV-7 was no longer detectable at 5 weeks, and the cornea remained clear without recurrence over 8 months. CONCLUSIONS: This case provides the first molecular and clinical evidence implicating HHV-7 as a causative agent of corneal epithelial infection. The clinical presentation closely resembled herpes simplex keratitis, and the favorable response to anti-herpetic therapy further supports its pathogenic role. HHV-7 should be considered in the differential diagnosis of dendritic or geographic keratitis even with typical terminal bulbs. Further research is warranted to clarify the corneal tropism, cellular entry mechanisms, and pathogenic potential of HHV-7. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12437-6.