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.

Applications of in vivo confocal microscopy in the management of infectious keratitis in veterinary ophthalmology

“…As a result of technical challenges, only corneal stromal nerves were analyzed in the study. Although no statistical differences in the two study groups were detected, a variety of nerve parameters (eg, nerve trunk numbers, branches, thickness, length, reflectivity, and tortuosity) were reduced in the cats with FHV‐1 exposure 91 …”

“…A study attempted to evaluate the corneal nerves in cats with, or without, previous feline herpesvirus‐1 (FHV‐1) exposure (based upon historical information and serology) using confocal microscopy performed post‐mortem 91 . As a result of technical challenges, only corneal stromal nerves were analyzed in the study.…”

“…90 A study attempted to evaluate the corneal nerves in cats with, or without, previous feline herpesvirus-1 (FHV-1) exposure (based upon historical information and serology) using confocal microscopy performed post-mortem. 91 As a result of technical challenges, only corneal stromal nerves were analyzed in the study. Although no statistical differences in the two study groups were detected, a variety of nerve parameters (eg, nerve trunk numbers, branches, thickness, length, reflectivity, and tortuosity) were reduced in the cats with FHV-1 exposure.…”

“…Although no statistical differences in the two study groups were detected, a variety of nerve parameters (eg, nerve trunk numbers, branches, thickness, length, reflectivity, and tortuosity) were reduced in the cats with FHV-1 exposure. 91 Descriptions of the IVCM features of active epithelial herpetic keratitis in human patients are limited. 92,93 In patients with herpes simplex virus dendritic keratitis, central dark regions representing the epithelial defect were present when examined by IVCM.…”

Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties

“…The cornea is the most densely innervated tissue in the human body [1]. Corneal nerves play a critical role in maintaining ocular surface health and homeostasis [2][3][4]. Disruption of corneal nerves often leads to serious detrimental effects [5,6] that can lead to lost or compromised innervation and result in neurotrophic keratopathy and blindness [2,[7][8][9].…”