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.

Keywords: confocal microscopy; corneal innervation; feline herpesvirus type 1; lacrimal functional unit; metaherpetic disease; nasolacrimal reflex.

Figure 1

Post-mortem confocal microscopy images of feline corneas, obtained during technique validation by approaching a freshly enucleated globe (A) or a globe in situ (B) with the confocal probe. Multiple dark lines observed in both images (small white arrows) represent fold artifacts that interfered with assessment of corneal stromal nerves (broad white arrows).

Figure 2

Post-mortem confocal microscopic images collected within 1 h of euthanasia of a FHV-1-naïve cat, with globes in situ and the third eyelid retracted using a cotton-tipped applicator. An unmodified image (A) as well as images demonstrating measurement of nerve thickness (B), nerve fiber length (C), and nerve occupancy (D) are shown. Images were assessed using NeuronJ software.