The measurement of corneal sensation allows clinicians to assess the status of corneal innervation and serves as a crucial indicator of corneal disease and eye health. Many devices are available to assess corneal sensation, including the Cochet-Bonnet aesthesiometer, the Belmonte Aesthesiometer, the Swiss Liquid Jet Aesthesiometer, and the newly introduced Corneal Esthesiometer Brill. Increasing the clinical use of in vivo confocal microscopy and optical coherence tomography will allow for greater insight into the diagnosis, classification, and monitoring of ocular surface diseases such as neurotrophic keratopathy; however, formal esthesiometric measurement remains necessary to assess the functional status of corneal nerves. These aesthesiometers vary widely in their mode of corneal stimulus generation and their relative accessibility, precision, and ease of clinical use. The development of future devices to optimize these characteristics, as well as further comparative studies between device types should enable more accurate and precise diagnosis and treatment of corneal innervation deficits. The purpose of this narrative review is to describe the advancements in the use of aesthesiometers since their introduction to clinical practice, compare currently available devices for assessing corneal innervation and their relative limitations, and discuss how the assessment of corneal innervation is crucial to understanding and treating pathologies of the ocular surface.

OBJECTIVE: To identify the stimulus airflow characteristics and confirm the consistency of a novel air jet-based aesthesiometer capable of producing and applying multiple stimuli separated either by time and/or by space.
METHODS: A novel aesthesiometer (Dolphin Aesthesiometer) was designed around a micro-blower under software management. Two nozzle attachments assisted in airflow control (flexible tube 1.6 mm diameter; brass tube 0.5 mm diameter). Four studies that tested the characteristics of the airflow and stimulus consistency were completed: (i) airflow pattern/trajectory, (ii) airflow surface dispersion, (iii) force of airflow across a range of stimulus strengths and (iv) thermal effects on the ocular surface.
RESULTS: Stimulus characteristic studies revealed: (i) airflow is coherent within the expected test distance range for the instrument, and spread rate is constant irrespective of stimulus strength; (ii) airflow dispersion occurs upon encountering a surface and dispersion increases with increasing airflow rate; (iii) a consistent and small force (10-4  N) is applied by the airflow and (iv) repeatable thermal effects occur in relation to the airflow, and the mode of stimulation of the Dolphin aesthesiometer is predominantly thermal in nature.
CONCLUSIONS: These studies confirm the repeatability and consistency of the novel instrument. The device is suitable for measuring corneal sensitivity. The availability of additional air jets allows the application of multiple stimuli to facilitate corneal summation investigations.

OBJECTIVE: To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes.
METHODS: Prospective, blinded crossover study.
METHODS: A group of 10 clinically healthy horses.
METHODS: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and T2, respectively), then 20 to 90 minutes (T3 to T10) at 10 minute intervals. CTT data were compared among treatments at each time point using the Friedman test p < 0.05.
RESULTS: Median (range) baseline CTT was 51.3 (25.0-60.0) mm for bupivacaine, 50.0 (40.0-55.0) mm for oxybuprocaine and 55.0 (30.0-60.0) mm for lidocaine. All treatments caused a significant decrease in CTT at T1. The lowest CTT was observed at T3 with bupivacaine and oxybuprocaine treatments. Median CTTs at this time point were 18.7 (5.0-25.0) mm and 28.7 (25.0-40.0) mm, respectively. The lowest CTT with lidocaine treatment was 28.7 (20.0-50.0) mm at T6 (50 minutes). At T3, CTT was significantly lower with the bupivacaine treatment compared with oxybuprocaine and lidocaine treatments (p < 0.0074). There was no significant difference in CTT values between T1 and T6 for bupivacaine, between T1 and T7 for lidocaine, and between T1 and T8 for oxybuprocaine. Duration of the maximum effect was 45 minutes for the bupivacaine, 55 minutes for the lidocaine and 65 minutes for the oxybuprocaine treatment.
CONCLUSIONS: Administration of a 0.5% injectable solution of bupivacaine or a 2% lidocaine had similar anaesthetic effect to the commonly used oxybuprocaine. Therefore, they might be used as alternatives for corneal anaesthesia.

OBJECTIVE: Explore potential of 31 tear biomarkers involved in screening for diabetic peripheral neuropathy (DPN). Assess the utility of aesthesiometry for measuring corneal damage in DPN and determine optimal cutoff point for detecting DPN.
METHODS: Screening test pilot study recruited 90 participants from a tertiary hospital in Lima, Peru. Participants were grouped by diabetes and neuropathy status. Tears collected on Schirmer strips, and proteins measured by both ELISA and multiplex-bead assay. Corneal sensitivity was measured by aesthesiometry, and DPN by vibration perception threshold testing.
RESULTS: There were 89 participants included in the analysis. The mean age was 55.7 ± 1.46, and 58.4% were female. MMP-9 and TGF-alpha concentrations were higher in participants with DPN versus diabetes alone, though not significant. Aesthesiometry was decreased in individuals with DPN when compared to participants with diabetes alone (p < 0.01) and normal controls (p < 0.01). Optimal cutoff point for aesthesiometry was found to be 5.8 cm, with 79% sensitivity and 75% specificity.
CONCLUSIONS: Tears are an insufficient standalone tool for detecting DPN based on the biomarkers analyzed. Aesthesiometry is a simple, inexpensive, and accurate method to assess corneal damage associated with moderate-severe DPN, and its integration into screening practices has potential to improve detection of DPN in poor-resource settings.

Background and objectives: The purpose of this study was to describe corneal sensitivity and the morphological changes of sub-basal corneal nerves using in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis-affected eyes, and to compare with both contralateral eyes and with the eyes of patients with a previous history of herpes labialis but no history of herpetic eye disease, and with healthy patients with no history of any HSV diseases, during the acute phase of the disease and after six months. Materials and Methods: A prospective clinical study included 269 patients. All of them underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM within the central 5 mm of the cornea. After six months, all the patients with herpetic eye disease underwent the same examination. Serology tests of the serum to detect HSV 1/2 IgG and IgM were performed. Results: HSV-affected eyes compared with contralateral eyes, herpes labialis and healthy control group eyes demonstrated a significant decrease in corneal sensitivity, corneal nerve fibre density, corneal nerve branch density, corneal nerve fibre length and corneal nerve total branch density (p < 0.05). During follow up after six months, corneal sensitivity and sub-basal nerve parameters had increased but did not reach the parameters of contralateral eyes (p < 0.05). Previous herpes labialis did not influence corneal sensitivity and was not a risk factor for herpetic eye disease. Conclusions: Corneal sensitivity and sub-basal nerve changes in HSV-affected eyes revealed a significant decrease compared with contralateral eyes, and with the eyes of patients with a previous history of herpes labialis, and of healthy controls. Following six months, corneal sensitivity and sub-basal nerve parameters increased; however, they did not reach the parameters of contralateral eyes and the eyes of healthy controls. The best recovery of corneal sensitivity was seen in patients with epithelial keratitis. Herpes labialis was not a risk factor for herpetic eye disease.

OBJECTIVE: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis/uveitis and contralateral, clinically unaffected eyes.
METHODS: A prospective clinical study included 30 HSV eyes and 30 contralateral eyes of 30 patients, diagnosed with unilateral HSV keratitis/uveitis. Both eyes underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM of the central cornea, using the Heidelberg Retina Tomograph III Rostock Cornea Module. After 6mo, the same examination of the HSV affected and contralateral, clinically unaffected eyes was performed.
RESULTS: HSV eyes, as compared to contralateral eyes, demonstrated a significant decrease in mean corneal sensation (3.1±1.6 vs 5.3±0.8 cm), total nerve fibres number (5.7±4.4 vs 15.1±5.4), nerve branches (3.4±3.0 vs 8.4±4.7), main nerve trunks (2.3±1.6 vs 5.8±2.2), and nerve fibres density (7.5±5.6 vs 18.1±5.3 mm/mm2, P<0.05). There was no significant difference between keratitis and uveitis eyes in mean corneal sensation and nerve fibres parameters. After 6mo, corneal sensation and sub-basal nerve fibres parameters were increased significantly, but did not reach the parameters of contralateral, clinically unaffected eyes.
CONCLUSIONS: Corneal aesthesiometry and LSCM in HSV affected eyes reveals a significant decrease of corneal sensation and sub-basal nerve fibres which recovers at 6mo but does not reach the normal level.

OBJECTIVE: To compare the degree and duration of corneal anesthesia of a novel viscous ophthalmic lidocaine hydrochloride preparation vs. two commonly used ophthalmic anesthetic preparations.
METHODS: Each subject was randomly selected to receive 2 of 4 treatments at 2 different time periods separated by a 1 week washout: 3.5% lidocaine hydrochloride gel (Akten® ; Akorn Inc., Lake Forest, Illinois, USA), 0.5% aqueous proparacaine hydrochloride (Akorn Inc.), 0.5% viscous tetracaine hydrochloride (TetraVisc™; Ocusoft Inc., Richmond, Texas, USA), or 0.9% saline eyewash as a negative control. Corneal sensitivity was determined using a Cochet-Bonnet aesthesiometer (Luneau® , Chartres Cedex, France) prior to instillation of each treatment; at 1 and 5 min post treatment; and at 5-min intervals thereafter for 90 min total. Ocular side effects were recorded on a scale of 0-3.
RESULTS: Twenty-four normal dogs (48 eyes) were entered into the study. Mean duration of maximal anesthesia was significantly greater at 34.2 min with tetracaine compared to 21.5 min and 19 min with proparacaine and lidocaine respectively. Corneal sensitivity was significantly decreased from baseline for up to 70 min with tetracaine and 55 min with both proparacaine and lidocaine. All lidocaine-treated eyes had transient blepharospasm and conjunctival hyperemia. Ten out of 24 tetracaine-treated eyes had conjunctival hyperemia with 4 of these having concurrent chemosis.
CONCLUSIONS: Tetracaine provided a significantly longer duration of corneal anesthesia than proparacaine or lidocaine. Tetracaine and lidocaine were associated with more ocular side effects than proparacaine, although these were mild and transient. None.

BACKGROUND: Circumferential (360°) endophotocoagulation is frequently implemented during vitrectomies for retinal detachment. This photocoagulation may result in neurotrophic keratitis by damaging the ciliary nerves in the suprachoroidal space on their way to the pupil. We report a series of 4 cases of neurotrophic keratitis following a circumferential endophotocoagulation.
METHODS: A retrospective observational case series of 4 non-diabetic patients having presented with a neurotrophic keratitis following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation (532 nm) at Caen University Hospital. We report the various forms of corneal lesions and the diagnostic criteria allowing for the diagnosis of neurotrophic keratitis.
CONCLUSIONS: Neurotrophic keratitis is caused by lesions occurring at various levels of corneal innervation. Endophotocoagulation may cause a neurotrophic keratitis by damaging the short and long ciliary nerves on their way to the pupil in the suprachoroidal space. The sequelae of this condition can limit visual recovery. Hence, it is probably advisable to screen for corneal anesthesia or severe hypesthesia following a retinal detachment treated with vitrectomy and circumferential endophotocoagulation and to implement prophylactic treatment (intensive lubricant therapy; preservative-free eye drops) if needed.
CONCLUSIONS: The risk of neurotrophic keratitis should be weighed against the dose of laser retinopexy necessary and sufficient to obtain a sustained retinal reattachment. If circumferential endophotocoagulation is implemented, it is probably sensible to monitor corneal sensitivity and to adapt postoperative treatment if necessary.

OBJECTIVE: To evaluate corneal sensitivity as measured by the corneal touch threshold in healthy bovine calves.
METHODS: Twelve clinically normal male calves with predominantly Holstein genetics and a median age of 76.5 days (range, 67-92 days).
METHODS: Corneal touch threshold (CTT) of the central cornea was measured in both eyes of each calf using a Cochet-Bonnet aesthesiometer.
RESULTS: The mean ± standard deviation corneal touch threshold of all eyes was 1.33 ± 1.1 g/mm(2) (range, 0.62-66.15 g/mm(2) ), corresponding to a filament length of 34.56 ± 8.02 mm (range, 14-47.5 mm). There was no significant difference between fellow eyes.
CONCLUSIONS: Cochet-Bonnet aesthesiometry was well tolerated in all 12 calves using a modified head restraint. Calves in this study may have a relatively sensitive central cornea compared to adult cattle and some other species; however, wide variation among individuals and eyes may be possible. Studies utilizing larger calf populations are necessary to establish reference ranges.

The objective of this study was to describe and compare the efficacy and duration of topical anaesthesia induced by 2 per cent lidocaine (L), 0.5 per cent bupivacaine (B) and 1 per cent ropivacaine (R) in the dog using 24 clinically healthy beagles with normal ocular examination. Dogs were randomly divided into three groups: 2 per cent lidocaine (n=8), 0.5 per cent bupivacaine (n=8) and 1 per cent ropivacaine (n=8). The baseline corneal touch threshold (CTT) was measured using a Cochet-Bonnet aesthesiometer. Following baseline CTT measurement, a single drop of the assigned anaesthetic was applied to each eye and the CTT was measured bilaterally within one minute after administration and every five minutes until the basal CTT value was restored. Data were analysed with non-parametric analysis of variance models and Dunnet\'s test for post hoc analysis. One per cent ropivacaine was the most effective drug (LCTTmax=3 cm, BCTTmax=2 cm, RCTTmax=0 cm; P<0.001), and had the shortest latency (LLatency=5 minutes, BLatency=5 minutes, RLatency=1 minute; P<0.001) and the smallest AUC (LAUC=80 cm×minute, BAUC=68.25 cm×minute, RAUC=36.88 cm×minute; P<0.001). There was no statistical difference in the duration of corneal anaesthesia between the groups (P=0.09) and all topical anaesthetics tested reduced corneal sensitivity, although 1 per cent ropivacaine had the maximal and quickest anaesthetic effect. This drug could be used for specific diagnostic procedures where quick and short, but effective, corneal anaesthesia is needed.