Altered Corneal Innervation and Ocular Surface Homeostasis in FHV-1-Exposed Cats: A Preliminary Study Suggesting Metaherpetic Disease

Abstract

Metaherpetic disease is recognized in humans affected by herpes simplex virus-1 but is not reported in cats affected by feline herpesvirus-1 (FHV-1) despite the high prevalence of herpetic disease in this species and strong similarities in viral biology between alphaherpesviruses of humans and cats. This preliminary work evaluated cats naïve to FHV-1 (n = 9 cats, 18 eyes; control population) and cats naturally exposed to FHV-1 (n = 4 cats, 7 eyes), as confirmed by serologic testing and review of medical records. Antemortem assessment included clinical scoring, blink rate, corneal aesthesiometry, tear film breakup time (TFBUT), and Schirmer tear test-1 (STT-1) with or without the nasolacrimal reflex. Post-mortem assessment involved confocal microscopy of the corneas and evaluation of corneal nerves with ImageJ. Groups were compared with Student's t-tests and results are presented as mean ± standard deviation. Compared to control, herpetic cats had significantly higher (P ≤ 0.010) clinical scores (0.2 ± 0.4 vs. 4.6 ± 2.8) and response to nasolacrimal stimulation (7.8 ± 10.8% vs. 104.8 ± 151.1%), significantly lower (P < 0.001) corneal sensitivity (2.9 ± 0.6 cm vs. 1.4 ± 0.9 cm), STT-1 (20.8 ± 2.6 mm/min vs. 10.6 ± 6.0 mm/min), TFBUT (12.1 ± 2.0 s vs. 7.1 ± 2.9 s), and non-significantly lower blink rate (3.0 ± 1.5 blinks/min vs. 2.7 ± 0.5 blinks/min; P = 0.751). All parameters evaluated for corneal nerves (e.g., nerve fiber length, branching, occupancy) were notably but not significantly lower in herpetic vs. control cats (P ≥ 0.268). In sum, cats exposed to FHV-1 had signs suggestive of corneal hypoesthesia and quantitative/qualitative tear film deficiencies when compared to cats naïve to the virus. It is possible these are signs of metaherpetic disease as reported in other species.