|Year : 2020 | Volume
| Issue : 3 | Page : 170-174
Establishing the normal range of corneal sensitivity in an Indian Population using the Cochet–Bonnet esthesiometer
Sharon Kotak1, Mini Christina2, Satheesh Solomon T. Selvin2
1 Optometrist, W.F. Pierce Memorial Hospital, Wai, Maharashtra, India
2 Department of Ophthalmology, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||04-Mar-2020|
|Date of Decision||21-Apr-2020|
|Date of Acceptance||05-May-2020|
|Date of Web Publication||10-Jul-2020|
Dr. Satheesh Solomon T. Selvin
Schell Eye Hospital, No 1, Arni Road, Vellore - 632 001, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: The human cornea is the most densely innervated tissue, and the corneal sensitivity is a measure of its function and an indicator of the integrity of the protective mechanism. Corneal sensitivity plays a vital role in the protection and maintenance of corneal health and is known to vary with race, age, region, climate, environment, and the time of the day. The study was aimed to quantify and establish the range of corneal sensations in different age groups in an Indian population using the Cochet–Bonnet Esthesiometer (CBE). Materials and Methods: This was a cross-sectional study done at a tertiary care center in South India, between January and April 2018. One hundred and fifty patients (30 patients stratified by age into five groups) were enrolled after informed consent. The corneal sensations were measured using CBE by a single examiner in a specified period of a day over five regions and the data analyzed. Results: The average measured corneal sensitivity was 58.36 (21–30 years), 57.96 (31–40 years), 56.43 (41–50 years), 56.40 (51–60 years), and 54.84 (>60 years) mm, respectively. The frequency of having maximal measurable sensations (60 mm) in all the tested regions dropped with increasing age from 46.67% to 16.67%. All regions showed a sensitivity drop with an increase in age, the maximum in the nasal quadrant and the least drop in the central region. No statistically significant difference in the corneal sensitivity was found between the genders. Conclusions: An inverse linear correlation between the corneal sensitivity and age was evident. The central and the superior regions are the most and least sensitive regions of the cornea, respectively, in our study population. The varied pattern of change in corneal sensations in different populations highlights the importance of establishing normal ranges of corneal sensitivity in patients from different ethnic and geographical backgrounds.
Keywords: Cochet–Bonnet, cornea, esthesiometer, sensation, sensitivity
|How to cite this article:|
Kotak S, Christina M, Selvin SS. Establishing the normal range of corneal sensitivity in an Indian Population using the Cochet–Bonnet esthesiometer. Curr Med Issues 2020;18:170-4
|How to cite this URL:|
Kotak S, Christina M, Selvin SS. Establishing the normal range of corneal sensitivity in an Indian Population using the Cochet–Bonnet esthesiometer. Curr Med Issues [serial online] 2020 [cited 2020 Oct 21];18:170-4. Available from: https://www.cmijournal.org/text.asp?2020/18/3/170/289412
| Introduction|| |
The cornea is the most densely innervated structure and hence the most sensitive tissue of the human body (containing about 7000 nociceptors/mm2), and is supplied by the nasociliary nerve of the ophthalmic branch of the trigeminal nerve. The nerve bundles enter the stroma and extend anteriorly and laterally, perforating the Bowman's layer and form a dense nerve plexus beneath the epithelial basement membrane. Corneal nerves are responsible for sensations of touch, pain, and temperature and play a significant role in the blink reflex, wound healing, tear production, and secretion. Ocular surface sensitivity is a measure of corneal nerve function and an indicator of the integrity of the protective mechanisms. Ocular surface sensations arise because of the stimulation of free nerve endings, which are activated as part of a protective mechanism.,,,,
Ocular surface disorders, including infections and trauma, surgical procedures, and ocular interventions including contact lens use and systemic diseases like diabetes mellitus and leprosy, are factors which have varied effects on the corneal sensitivity by disrupting the corneal innervations. Physiological factors as well are known to affect corneal sensitivity such as the diurnal variation, iris pigmentation racial variations, ultraviolet (UV) exposure, environment, and corneal test location also can account for significant differences in the measured corneal sensitivity.
Till the year 1896, it was believed that the cornea had only pain sensation and could not feel touch until von Frey made his first esthesiometer, and tested using different lengths of hair to test the tactile sensibility of the cornea. Later in 1955, Boberg-Ans, substituted with a nylon thread of different lengths, which was later modified by Cochet and Bonnet with two filaments of different thicknesses which allowed different ranges of pressure to be applied and measured. Other methods were with chemical stimulation using capsaicin and thermal stimulation using the carbon diode laser, however, these methods were expensive and did not gain popularity in clinical practice. In the current clinical practice, corneal sensations are measured qualitatively with a wisp of cotton, but quantitative measurements are useful in unusual cases and research. Esthesiometry is the measurement of corneal sensation, specifically assessing and quantifying the tactile perception of the cornea. One of the most common instruments available is still the Cochet–Bonnet Esthesiometer (CBE), which operates by applying pressures to the ocular surface through alteration of the length of the nylon filament. This senses the mechano-nociceptor response to a non invasive mechanical stimulus, thereby quantifying the touch.
To establish an abnormal corneal sensitivity, the normal value of corneal sensations must be known within a population. Although there are studies done in the Asian population, the results are not conclusive to quantify the same in an Indian population. Moreover, there are known variations seen between regions, races, and the values that can be influenced by climatic variations. The study was designed to establish the normal range of corneal sensations stratified by age groups and in the different regions of the cornea in an Indian population.
| Materials and Methods|| |
This was a cross-sectional study conducted at a tertiary care center in Southern India between the months of January and June 2018. The study protocol was approved by the Institutional Review Board and the Ethics Committee (IRB minute number: 11095; Dated 10.01.2018).
Sample size calculation
Based on the study done by Booranapong et al. in Thailand and using the formula for a two-mean comparison, a minimum of 30 participants (30 eyes) in each arm was required to obtain a statistical mean difference of two units in the corneal sensitivity between each age group, with a standard deviation of 2.5 units, a power of 80% and a significance level of 5%.
The first ten patients of 21 years of age or above, who were registered for the outpatient clinic visit on the study days satisfying the inclusion and exclusion criteria were enrolled after informed consent. Patients with a history of contact lens wear, history of ocular trauma, history of ocular infection or inflammation or dry eyes, corneal pathologies, systemic diseases are known to affect corneal sensitivity like Diabetes or Hansen's disease, use of topical medications, history of the ocular surface, intraocular or corneal surgeries, one-eyed patients, developmentally challenged and uncooperative patients, patients with neurological disorders or the fifth cranial nerve palsies were excluded from the study.
Patient's demographic data and history were noted by the primary investigator. Following which, the secondary investigator who was blinded to the demographic data of the patient assessed the corneal sensitivity as per the standard operating protocol of the instrument (CBE, Luneau Ophthalmologia, France). The right eye was chosen as the study eye by default. The patients were positioned at the slit-lamp (for stabilization of the head during assessment) with his/her chin on the chin rest and forehead resting against the forehead rest. The illumination of the room was dimmed, lest it caused a glaring effect to avoid a false-positive result. The study was carried out in the same room for all the patients and was done during a defined period of the day (9:00 am to 11:00 am). This was ensured and followed to avoid temperature influence or variance.
The readings of the corneal sensitivity were assessed by placing the instrument with the filament perpendicular to the cornea and checking for the response. Readings were taken in sequential order and were recorded around 1.5–2 mm inside the limbus at the 12, 9, 6, and 3 O'clock position and finally in the central region of the cornea. The length of the filament was kept at 60 mm (0.4 g/mm2) at the start of the assessment. The positive response was observed in the form of blink on touching the cornea or when the patient claimed to have felt it along with the visible bend of the filament. A negative response was defined as the no response or an absent blink on the visible bending of the filament. After a negative response, the filament was retracted by 5 mm each time, and the test repeated until a positive response was obtained. The first positive response was taken as the reading for the particular region/response. An absent response was defined as the negative response to the shortest length (5 mm) of the filament that can be used for the measurement.
After the readings were taken, the filament was cleaned using the standard operating protocol and air-dried as recommended by the manufacturer, before the assessment was carried out on the next patient. At the end of the outpatient department clinic, the medical records were analyzed to screen for exclusion criteria.
Grouping of patients
The patients were sub-grouped according to their age into five sub-groups: Group 1 (21–30), Group 2 (31–40), Group 3 (41–50), Group 4 (51–60), and Group 5 (>60) years of age respectively, for analysis. Patients were enrolled in all the sub-groups until each group had 30 patients.
Categorical variables were summarized using frequencies and percentages. Quantitative variables were summarized using the mean and standard deviation or median and IQR. One way analysis of variance was used to compare the means between more than one age group and the corneal sensitivity. Pearson correlation or Spearman's rank correlation and Bartlett's test of equal variance was used to find the relationship between age and corneal sensitivity. For all the analyses, 5% level of significance was considered to be significant. All the statistical analysis was performed using STATA version 13.1 is the statistical software by StataCorp, Texas, USA.
| Results|| |
A total of 150 patients were needed to achieve a sample size of 30 patients in each of the subgroups, as categorized by age. There were 81 (54%) male patients and 69 (46%) female patients who participated in our study, with the majority of them from Tamil Nadu (54.42%). [Table 1] gives the average values and the raw data of the mean corneal sensitivity in the five subgroups categorized by age and in the five regions tested with CBE.
|Table 1: Raw data of the mean corneal sensitivity in the study sub-groups and in the corneal regions tested with the Cochet Bonnet Esthesiometer|
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The number of patients who had a maximal possible measurable corneal sensitivity of 60 mm in all the five corneal regions tested was 46.67% in Group 1 and the percentage of which decreased by 30% when compared to Group 5 in the oldest age group [Figure 1]. The average corneal sensations assessed over the five corneal regions tested, when analyzed individually showed the highest sensitivity in the younger age group (Group 1) with a linear decrease as the age progressed towards the older age groups [Figure 2]. Though a gradual decrease in the sensitivity with age is observed throughout in all the regions tested, the superior quadrant was consistently the least sensitive region and the central the most sensitive of all the regions measured.
|Figure 1: Pie chart showing the percentage of patients that had a recorded corneal sensitivity of 60 mm (length of the filament) in all the five corneal regions as tested using the Cochet-Bonnet Esthesiometer.|
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|Figure 2: Line graph showing the decrease in mean corneal sensitivity in each corneal region with age as tested with Cochet Bonnet Esthesiometer.|
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The average corneal sensitivity of the five regions tested in the male and female patients was 57.27 and 56.41 mm in female and male patients, respectively. [Figure 3] shows the drop in each of the corneal regions tested between the first and the last group as categorized with age.
|Figure 3: The drop in the mean corneal sensitivity as tested with the Cochet Bonnet Esthesiometer between group 1 and group 5 in our study population.|
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| Discussion|| |
The cornea is one of the most densely innervated tissues in the human body and is richly supplied by sensory and autonomic nerve fibers. In human corneas, the nerve bundle moves from the periphery to the center and exerts important neuro-modulatory effects on corneal epithelial physiology, including regulation of ion transport; cell proliferation, differentiation, adhesion, and migration; and wound healing. Damage to the corneal nerves by surgery, trauma, or disease deprives the corneal epithelium of essential neurotrophic influences. In our study, we aimed to establish the normal corneal sensitivity in an Indian population in different age populations, as ethnic and environmental factors could influence this value.
Corneal sensation decreases after the fifth decade, as shown by Millodot, which was in accordance with the results obtained by Boberg-Ans,, Cochet and Bonnet. The study by Jalavisto et al. also found that diurnal variation with a higher corneal sensitivity in the afternoon as compared to the morning, which was consistent with the observations by Millodot. In our study, to avoid the diurnal variation and the temperature influencing our measurements, the measurements were taken between 9 am and 11 am on the study days and in the same examination room. The average temperature on the study days was 29.02°C with a maximum of 32°C and a minimum of 23°C. The study by Millodot showed no statistical difference between genders. In our study, too there was no statistically significant difference (P = 0.6) sensitivity between genders on applying the two sample t-test with equal variances. The mean average of corneal sensitivity among the female patients (57.27 mm) was, however, marginally higher and clinically insignificant as compared to male patients (56.41 mm).
On the categorization of the patients into five age-groups, it was evident that the mean corneal sensitivity of the five corneal regions tested had a linear drop with increasing age [Figure 2]. The difference in the mean corneal sensitivity between Groups 1 and 2, when compared with Group 5, was statistically significant with Bartlett's test of equal variance. [Table 1] and [Figure 2] show the decreasing trend in corneal sensitivity in each of the five areas tested with advancing age. In our study, the drop in the individual regions tested was found to be highest in the nasal quadrant, followed by the superior, inferior, temporal, respectively when compared between Groups 1 and 5 [Figure 3]. The nasal quadrant having the highest drop could be attributed to the fact that the nasal limbus is the most affected region of the ocular surface by UV rays from the sun and hence a greater drop in the sensations. This is further supported by the fact that the nasal side has the most common occurrence of pterygiums, due to the same etiology of the effect of UV radiation., Bartlett's test for equal variance showed statistical significance for the measured drop of the inferior, nasal, and central quadrants. This finding could be the reflection of the higher measured values in these regions in the younger age groups and hence, a possible greater measurable drop in the sensations.
The central region had the highest corneal sensations recorded as compared to the superior quadrant, which was measured the least in our study, the results of which is consistent with the study done by Mirzajan et al. Inherently, the central region of the cornea has the densest distribution of the sensory receptors and hence the highest sensitivity. However, anatomical studies have shown no major differences in the distribution of corneal nerves in the four corneal quadrants. The probable explanation for the superior quadrant to have the least sensations is the frequent coverage by the upper eyelid and causing oxygen deprivation. This possibly results in a decreased acetylcholine (ACh) or (choline acetyltransferase, the enzyme that synthesizes ACh) in the corneal epithelium leading to a decreased sensitivity.,
A bird's eye view [Figure 4] of the various similar studies from different geographical regions comparing the central corneal sensitivity is shown as compared to our study. It is evident that it decreases significantly after the age of 60 in our study as compared to a mean age of 36 years in Iran and after the age of 50 in Italy, respectively. The drop in the central corneal sensitivity, as measured in our study, showed a close similarity to the study done in the Thai population by Booranapong et al. The different age cut off before the drop in the sensations and the average drop of the corneal sensitivity was attributed to the difference in the climate, which is tropical in Iran and temperate in Thailand., Furthermore, the delay in the sensations to significantly drop may be attributed to racial variations and a possible indirect connection to the improved health care that could be slowing down the aging process. Amongst other factors iris pigmentation as shown by Millodot to cause a variation could be a factor in finding this similar variation in our study. However, this needs to be studied further. One must be aware of these factors during the assessment of corneal sensitivity, and a normal variation should not be read as a potential marker for conditions associated with corneal neuropathy.
|Figure 4: Line graph showing the comparison of the average central corneal sensitivity of the Indian population with that of the Thai, Italian and the Iranian population.|
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| Conclusions|| |
The corneal sensations in all the regions decreased linearly with age after the third decade of life, with a significant reduction seen after the sixth decade in an Indian population. The most sensitive area was the central region, and the least sensitive was the superior peripheral quadrant of the corneal surface. The nasal quadrant and the central region had the highest and the least drop, respectively, in sensations with age in our study population. To understand the variations in the corneal sensations across diverse geographic and ethnic backgrounds, it may be prudent to formulate and establish normative ranges to make useful comparisons in similar populations.
The authors hereby acknowledge Ms. Hepsy Chelliah, Department of Biostatistics, Christian Medical College, Vellore for the inputs and support in the study analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Research quality and ethics statement
The authors of this manuscript declare that this scientific work complies with reporting its IRB Min no: 11095; dated 10.01.2018. We also certify that we have not plagiarized quality, formatting and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation was determined to require Institutional Review Board/Ethics Committee review, and the corresponding protocol/approval number the contents in this submission and have done a Plagiarism Check.
| References|| |
Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol 2018;66:190-4.
] [Full text]
Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: Structure, contents and function. Exp Eye Res 2003;76:521-42.
Tavakoli M, Petropoulos IN, Malik RA. Assessing corneal nerve structure and function in diabetic neuropathy. Clin Exp Optom 2012;95:338-47.
Oliviera-Sotto L, Effron N. Morphology of corneal nerves using a confocal microscope. Cornea 2011;20:374-84.
Guthoff RF, Wienss H, Hahnel C, Wree A. Epithelial innervation of human cornea: A three-dimensional study using confocal laser scanning fluorescence microscopy. Cornea 2005;24:608-13.
Khanal S, Tomlinson A, Esakowitz L, Bhatt P, Jones D, Nabili S, et al
. Changes in corneal sensitivity and tear physiology after phacoemulsification. Ophthalmic Physiol Opt 2008;28:127-34.
Millodot M. Effect of long-term wear of hard contact lenses on corneal sensitivity. Arch Ophthalmol 1978;96:1225-7.
Kyprianou I, Mollan SP, Tsaluomas MD, Jacks AS. Corneal sensation: A test not to omit. Arch Neurol 2006;63:1656-7.
Millodot M. Diurnal variation of corneal sensitivity. Br J Ophthalmol 1972;56:844-7.
Millodot M. Do blue-eyed people have more sensitive corneas than brown-eyed people? Nature 1975;255:151.
Julio G, Campos P, Pujol P, Munguia A, Mas-Aixala E. Determining factors for fast corneal sensitivity recovery after pterygium excision. Cornea 2016;35:1594-9.
Millodot M, O'Leary DJ. Effect of oxygen deprivation on corneal sensitivity. Acta Ophthalmol (Copenh) 1980;58:434-9.
Boberg-Ans J. Experience in clinical examination of corneal sensitivity; corneal sensitivity and the naso-lacrimal reflex after retrobulbar anaesthesia. Br J Ophthalmol 1955;39:705-26.
Boberg-Ans J. On the corneal sensitivity. Acta Ophthalmol (Copenh) 1956;34:149-62.
Cochet P, Bonnet R. Anesthésie corneenne. Clin Ophthalmol 1960;4:3-27.
Belmonte C, Acosta MC, Schmelz M, Gallar J. Measurement of corneal sensitivity to mechanical and chemical stimulation with a CO2 esthesiometer. Invest Ophthalmol Vis Sci 1999;40:513-9.
Pullen RL Jr. Testing the corneal reflex. Nursing 2005;35:68.
Larson WL. Electro-mechanical corneal aesthesiometer. Br J Ophthalmol 1970;54:342-7.
Chao C, Stapleton F, Badarudin E, Golebiowski B. Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer. Optom Vis Sci 2015;92:183-9.
Booranapong W, Tanthuvanit P, Suwannik A. Corneal sensation in the normal Thai population. Siraj Med J 2005;57:262-5.
Martin XY, Safran AB. Corneal hypoesthesia. Surv Ophthalmol 1988;33:28-40.
Thorgaard GL, Holland EJ, Krachmer JH. Corneal edema induced by cold in trigeminal nerve palsy. Am J Ophthalmol 1987;103:641-6.
Millodot M. The influence of age on the sensitivity of the cornea., Invest Ophthalmol Vis Sci 1977;16:240-2.
Jalavisto E, Orma E, Tawast M. Ageing and relation between stimulus intensity and duration in corneal sensibility. Acta Physiol Scand 1951;23:224-33.
Millodot M. A review of research on the sensitivity of the cornea. Ophthalmic Physiol Opt 1984;4:305-18.
Maloof AJ, Ho A, Coroneo MT. Influence of corneal shape on limbal light focusing. Invest Ophthalmol Vis Sci 1994;35:2592-8.
Mirzajan A, Khezri F, Jafarzadehpur E, Karimian F, Khabazkhoob M. Normal corneal sensitivity and its changes with age in Tehran, Iran. Clin Exp Optom 2015;98:54-7.
Murphy PJ, Patel S, Kong N, Ryder RE, Marshall J. Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects. Invest Ophthalmol Vis Sci 2004;45:1737-42.
Roszkowska AM, Colosi P, Ferreri FM, Galasso S. Age-related modifications of corneal sensitivity. Ophthalmologica 2004;218:350-5.
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