NK is a degenerative disease characterized by damage to trigeminal (V cranial nerve) ophthalmic branch innervation. Trigeminal nerve integrity is necessary to maintain the tropism, survival, and function of the ocular surface cells through the release of mediators and growth factors that maintain ocular surface health and homeostasis [1]. Therefore, the damage of corneal innervation leads to impairment of corneal healing, spontaneous epithelial breakdown, recurrent or persistent epithelial defects, and corneal ulcers. Various conditions can cause damage of the trigeminal nerve including herpetic keratitis, diabetes, intracranial mass, iatrogenic injury following neurosurgery, ocular burns, contact lens use, ocular surgery, and chronic use of topical drugs [2]. NK is classified according to the severity of corneal damage: cloudy, irregular corneal epithelium and/or superficial punctate keratopathy (stage I), persistent epithelial defect (stage II), and corneal ulcer (stage III), that can lead to corneal perforation and loss of visual function [3]. Currently, patients affected by NK can be treated with tear substitutes, therapeutic contact lenses and nerve growth factor eye drops [4,5]. However, when a corneal ulcer persists, an amniotic membrane transplant, conjunctival flap, or tarsorrhaphy are necessary to restore the ocular surface integrity [6].

Diagnosis of NK is clinical and remains challenging for the clinician. It requires a thorough clinical history that should be consistent with trigeminal nerve injury. Subjectively, the patient usually complains of mild ocular discomfort or has no complaints at all. Therefore, a complete eye examination must be performed to detect corneal and conjunctival signs of NK. A decrease or absence of corneal sensitivity (CS) is necessary to confirm the diagnosis of NK [7]. CS may be qualitatively assessed by cotton thread or quantified by corneal aesthesiometer [7]. Currently, a specific cut-off value of CS that could help with the diagnosis of NK has not been demonstrated. The Cochet-Bonnet esthesiometer (1960) is currently the gold standard tool, used in clinical and research settings [8]. A thin, retractable, nylon 0.12 mm diameter filament, that extends from 5 mm to 60 mm, touches the anterior surface of the cornea in all quadrants. A variable pressure is applied by adjusting the length to elicit a blink reaction or a patient response by stimulating the mechanosensitive Aδ nerve fibres. The length of the filament needed to induce a patient's feedback will quantify the corneal mechanical sensitivity threshold [2]. Some limitations of CB include the requirement of sterilization after each use, the high cost, and the variable reproducibility of results due to difficulties in alignment, positioning, and repeatability of the applied pressure. Ambient humidity and aging fibres can also limit the accuracy of the measurement [9]. Non-Contact Corneal Aesthesiometers (NCCA) have been developed as a safer alternative to CB esthesiometer for corneal esthesiometry assessment following surgery. However, repeatable, reproducible central corneal alignment for the measurement has yet to be achieved and NCCA is not commonly used in clinical settings. Moreover, the two devices analyse different components of corneal innervation [10].

Therefore, the need for a safe, simple, disposable device to be used in daily practice has led to the development of a novel single-use esthesiometer (KeraSenseⓇ, Dompè farmaceutici Spa, Milan Italy) to test corneal mechanical sensitivity. This tool ensures better safety and sterility for the patient, but, as of today, it has not been validated.

This study aims to assess sensitivity, specificity, and cut-off values of CS for the diagnosis of NK. In addition, this study aimed to evaluate the novel, single use esthesiometer, in comparison to CB, in terms of accuracy, reproducibility, and repeatability.