Viral eye: Emerging insights into corneal and ocular surface viral infections

Table 1 Summary of major viral ocular surface infections

Virus	Main clinical features	Key diagnostic tools	Typical management	Prognostic considerations	Key emerging developments/future directions
HSV	Recurrent epithelial and stromal keratitis; risk of corneal scarring and neurotrophic keratopathy	Slit-lamp exam; PCR for HSV DNA; in vivo confocal microscopy	Topical or oral antivirals (acyclovir, valacyclovir); corticosteroids for stromal disease	High recurrence rate; vision loss from scarring and thinning	rhNGF for neurotrophic keratopathy[28]; sustained-release/nanocarrier antivirals[70]
Adenovirus	Epidemic keratoconjunctivitis; subepithelial infiltrates; highly contagious outbreaks	Clinical exam; rapid antigen tests; multiplex PCR	Supportive care; off-label antivirals under investigation; topical steroids for infiltrates	Usually self-limited; infiltrates may persist and cause visual disturbance	Receptor-blocking agents (multivalent sialic-acid conjugates, GAG mimetics)[42,43]; CRISPR–Cas9 strategies[45]; adjunct 5% povidone-iodine (select settings)[39]
CMV	Corneal endotheliitis, keratic precipitates, ocular hypertension; common post-keratoplasty	PCR of aqueous humor; specular microscopy; mNGS in refractory/atypical cases	Topical ganciclovir; oral valganciclovir for refractory disease	Recurrent disease leads to endothelial loss and graft failure	mNGS to clarify atypical presentations[53]; next-generation antivirals (letermovir, maribavir) for resistant cases[57,58]; adoptive virus-specific T-cells in refractory disease[56]
HPV	OSSN, from CIN to invasive carcinoma	PCR for HPV DNA; p16 IHC; E6/E7 mRNA in situ hybridization	Surgical excision ± cryotherapy; topical IFN-α2b, MMC, 5-FU	Recurrence risk higher in immunosuppressed patients	Potential indirect prevention via HPV vaccination (genotypes 16/18/33 prevalent in HPV-positive OSSN)[59,60]; immune checkpoint inhibitors in advanced cases[69]; RNA-ISH for E6/E7 to identify HPV-driven disease[64]

HSV: Herpes simplex virus; NGF: Nerve growth factor; rhNGF: Recombinant human nerve growth factor; CMV: Cytomegalovirus; mNGS: Metagenomic next-generation sequencing; HPV: Human papillomavirus; OSSN: Ocular surface squamous neoplasia; CIN: Conjunctival intraepithelial neoplasia; IFN: Interferon; MMC: Mitomycin-C; 5-FU: 5-fluorouracil; IHC: Immunohistochemistry; RNA-ISH: RNA in situ hybridization; GAG: Glycosaminoglycan.