Qualitative method (cotton wisp test)
Equipment: A thin wisp pulled from the tip of a cotton swab.
Method: Compare sensation in all 4 quadrants of both eyes
Recording: Three levels: normal, reduced, absent
Advantages: Easily available and simple
Corneal esthesiometry is a test that measures corneal sensitivity (mainly tactile sensation). It evaluates the function of the ophthalmic nerve, the first branch of the fifth cranial nerve (trigeminal nerve). The cornea has the highest density of sensory nerves in the body, with a density 300–400 times that of the skin and 40 times that of the oral mucosa.
Corneal sensitivity plays an important role in triggering tear secretion, maintaining corneal epithelial homeostasis, and signaling pathological conditions of the cornea. When corneal sensitivity decreases, protective reflexes are lost, and corneal epithelial damage tends to progress.
The first esthesiometer was reported by von Frey in 1894. It used horse hairs of different lengths. In 1932, Francheschetti improved this model. In 1956, Boberg-Ans reported a device using a single nylon filament of constant diameter but variable length.
Cochet and Bonnet further improved this model and developed an esthesiometer using a nylon filament with a diameter of 0.12 mm. It is currently the most widely used quantitative esthesiometer.
Decreased corneal sensitivity (corneal hypoesthesia) can result from any cause that damages the corneal nerves or the trigeminal nerve.
| Category | Typical Causes |
|---|---|
| Infectious diseases | Corneal herpes (HSV/VZV) |
| Systemic diseases | Diabetes mellitus, multiple sclerosis |
| Post-surgery | Corneal transplant, LASIK, cataract surgery |
| Contact lenses | Hypoesthesia due to long-term wear |
| Drug-induced | Beta-blockers, NSAIDs, diclofenac |
| Intracranial lesions | Acoustic neuroma, aneurysm |
| Congenital | Congenital corneal anesthesia |
Herpes simplex keratitis is one of the most common causes of decreased corneal sensation. In diabetes, corneal sensation decreases in correlation with the severity of retinopathy, and it is known that the morphology of corneal nerves changes in correlation with renal function.
NSAID eye drops can also cause decreased corneal sensation and should not be overlooked.
Raj et al. (2022) reported a case of neurotrophic keratitis in a patient after corneal transplantation who continued to use bromfenac eye drops incorrectly 2). The neurotrophic effect due to the analgesic action of NSAIDs and activation of matrix metalloproteinases are speculated as mechanisms 2).
Congenital corneal anesthesia is an extremely rare condition.
Gelzinis et al. (2022) reported a pediatric case with congenital corneal anesthesia due to bilateral trigeminal nerve hypoplasia 5). Sensory function assessment using a Cochet-Bonnet esthesiometer and morphological evaluation of the trigeminal nerve by MRI were useful for diagnosis 5).
When corneal sensation decreases, the protective reflexes of the eye (blinking, tear secretion) are weakened, making corneal epithelial damage more likely to progress. This is called neurotrophic keratitis. Early stages show punctate keratopathy, progression leads to persistent epithelial defects, and severe cases can result in corneal ulceration or perforation. Because pain is less noticeable, detection is often delayed, making regular corneal sensation testing important.
Corneal sensation testing includes qualitative methods and quantitative methods. Do not use topical anesthetic eye drops before testing. Always check whether anesthetic eye drops have been used in other tests beforehand.
Qualitative method (cotton wisp test)
Equipment: A thin wisp pulled from the tip of a cotton swab.
Method: Compare sensation in all 4 quadrants of both eyes
Recording: Three levels: normal, reduced, absent
Advantages: Easily available and simple
Quantitative method (Cochet-Bonnet type)
Instrument: Retractable nylon monofilament
Method: Shorten from 60 mm in 5 mm steps to measure threshold
Recording: Minimum detectable length (mm)
Advantages: High reproducibility and quantitative assessment
This is the most commonly used method in clinical practice. A wisp of cotton from a cotton-tipped applicator is used to compare corneal sensation between both eyes. Approach from the patient’s side and test all 4 quadrants of the cornea. Record sensation at each site as “normal,” “reduced,” or “absent.” Dental floss can also be used.
Epitropoulos et al. (2022) reported a retrospective case series of 4 patients with stage 1 neurotrophic keratitis, in which qualitative assessment using dental tape recorded corneal sensation in the central and peripheral regions3).
If a Cochet-Bonnet esthesiometer is not available, a cotton ball can be moistened, squeezed well, twisted into a thin wisp, and touched to the cornea to obtain information about reduced sensation.
Raj et al. (2022) assessed corneal sensation using a cotton-tipped applicator during the COVID-19 pandemic when the Cochet-Bonnet esthesiometer was unavailable2).
This is the most widely used device for quantitative assessment. It consists of a 0.12 mm diameter nylon filament that can be extended or retracted via a dial, changing the pressure applied to the cornea. Shorter lengths produce higher pressure. The Cochet-Bonnet score ranges from 5 mm to 60 mm, with lower values indicating more severe hypoesthesia6).
Procedure:
Corneal sensitivity is highest in the central area and decreases toward the periphery, so comparisons should be made at the same location.
Kymionis et al. (2025) confirmed a marked decrease in corneal sensitivity using the Cochet-Bonnet esthesiometer in the diagnosis of herpes simplex virus neurotrophic keratitis, and used it to confirm the clinical diagnosis1).
For research purposes or complex cases, the following methods may be used.
In vivo confocal microscopy is a non-invasive method to observe the corneal subepithelial nerve plexus. It is useful as a morphological assessment that complements quantitative evaluation of corneal sensation.
Gouvea et al. (2021) confirmed a decrease in corneal subepithelial nerve plexus density using confocal microscopy in a case of neurotrophic keratitis associated with lattice corneal dystrophy, and observed improvement in nerve plexus density after cenegermin treatment4).
In the Cochet-Bonnet esthesiometer test, the tip of the nylon thread only lightly touches the cornea, so there is no strong pain. However, since the test must be performed without anesthesia, you may feel a slight discomfort at the moment of contact. The test itself takes only a few minutes.
The sensory innervation of the cornea is provided by the nasociliary nerve, a branch of the first division of the trigeminal nerve (ophthalmic nerve). The long ciliary nerves branch from the nasociliary nerve, penetrate the sclera, and reach the cornea.
Corneal nerves first run as myelinated fibers within the stroma, lose their myelin sheath when penetrating Bowman’s layer, and become unmyelinated fibers. They form a rich nerve plexus (subepithelial nerve plexus) beneath the corneal epithelium.
Corneal sensation has the following characteristics.
Corneal nerves have two functions: sensory function and trophic function. The sensory function transmits pain and foreign body sensation, inducing blink reflex and tear secretion. The trophic function releases neurotransmitters such as nerve growth factor (NGF), substance P, and calcitonin gene-related peptide, maintaining corneal epithelial proliferation, migration, adhesion, and differentiation.
Cenegermin, a recombinant human nerve growth factor (rhNGF) ophthalmic solution, has received FDA approval for neurotrophic keratitis. In addition to promoting corneal epithelial healing, recovery of corneal sensation has also been reported.
Epitropoulos et al. (2022) administered cenegermin (20 µg/mL, 6 times daily for 8 weeks) to 4 cases of stage 1 neurotrophic keratitis, and all cases showed improvement in corneal sensation and reduction of punctate epithelial erosions3).
Gelzinis et al. (2022) used cenegermin for a corneal ulcer in a child with congenital corneal anesthesia, achieving corneal epithelial healing5). However, recovery of corneal sensation was limited in cases of severe congenital sensory impairment5).
Corneal neurotization is a surgical approach that transfers healthy sensory nerves (such as the supraorbital, supratrochlear, and infraorbital nerves) to the cornea to restore corneal sensation6). There are two surgical techniques: direct method (direct transfer of donor nerve) and indirect method (transfer via autologous nerve graft)6). Recovery of corneal sensation is achieved within a few months postoperatively, and stabilization of the corneal epithelium and improvement in long-term prognosis have been reported6).
Kymionis et al. (2025) reported a case of persistent epithelial defect due to herpes simplex virus neurotrophic keratitis treated with allogeneic anterior lens capsule transplantation (ALCT), achieving complete epithelialization within 2 weeks1). The anterior capsule is obtainable during cataract surgery and has the advantage of superior transparency compared to amniotic membrane1).
- Kymionis GD, Vakalopoulos DG, Chatzea MS, Togka KA, Tsagkogiannis VA, Petrou PC. Allogeneic anterior lens capsule transplantation (ALCT) for the management of 単純ヘルペスウイルス neurotrophic keratitis. Am J Ophthalmol Case Rep. 2025;38:102292.
- Raj N, Panigrahi A, Alam M, Gupta N. Bromfenac-induced neurotrophic keratitis in a corneal graft. BMJ Case Rep. 2022;15:e249400.
- Epitropoulos AT, Weiss JL. Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment. Am J Ophthalmol Case Rep. 2022;27:101649.
- Gouvea L, Penatti R, Rocha KM. Neurotrophic keratitis after penetrating keratoplasty for lattice dystrophy. Am J Ophthalmol Case Rep. 2021;22:101058.
- Gelzinis A, Simonaviciute D, Krucaite A, Buzzonetti L, Dollfus H, Zemaitiene R. Neurotrophic Keratitis Due to Congenital Corneal Anesthesia with Deafness, Hypotonia, Intellectual Disability, Face Abnormality and Metabolic Disorder: A New Syndrome? Medicina. 2022;58:657.
- Rosenblatt MI, et al. Corneal neurotization for the treatment of neurotrophic keratopathy. Curr Opin Ophthalmol. 2025;36:294-301.