DOI: 10.1111/dme.12125 The acceptability and feasibility of corneal confocal microscopy to detect early diabetic neuropathy in children: a pilot study Diabet. Med. 30, 630–631 (2013) The American Diabetes Association endorses screening for retinopathy and nephropathy, but not neuropathy in children with Type 1 diabetes [1]. This may reflect the lack of an easily deployed assessment technique with a high sensitivity and specificity for the detection of early neuropathy in children. Neurophysiologic assessments have a high sensitiv- ity, but are not performed easily in children. Vibration and tactile perception thresholds are easily performed, but have poor sensitivity and specificity in children [2]. Clinical examination including vibration and tactile perception did not detect neuropathy in our population of children with Type 2 diabetes [3] and yet in follow-up of the first cohort of childhood-onset Type 2 diabetes in Manitoba, lower limb amputations occurred in the third decade [4]. Thus, there is a need for non-invasive sensitive screening tools to detect early diabetic neuropathy in children with diabetes. In adults with diabetes, corneal confocal microscopy is a rapid, well-tolerated, non-invasive test to identify early small nerve fibre damage and quantify the severity of neuropathy [5,6]. Similar studies have not been carried out in children. The aim of this pilot study was to evaluate the acceptability and feasibility of corneal confocal microscopy in children. Children with either Type 1 or Type 2 diabetes and healthy volunteers were recruited sequentially from the paediatric diabetes or general clinics at the Children’s Hospital, Winnipeg, Canada. The study was approved by the Human Research Ethic Board, Faculty of Medicine, University of Manitoba. Written informed consent and assent was obtained from the parent/guardian and child, respectively. Children were excluded if they had previous disease, trauma or surgery of the eye, non-diabetic neurop- athy or any serious chronic illness other than diabetes. All participants underwent corneal confocal microscopy using the Heidelberg Retina Tomograph Cornea Module (Heidelberg Engineering, Vista, CA, USA). One eye was randomly selected and anaesthetized with a drop of Alcaine (proparacaine hydrochloride 0.5%; Alcon, Mississauga, Ontario, Canada). A drop of Genteal Gel (0.3% hypromel- lose; Novartis Ophthalmics, Mississauga, Ontario, Canada) was placed on the tip of the objective lens and a sterile disposable Tomo cap was placed over the lens, allowing optical coupling of the objective lens to the cornea to focus on Bowman’s layer. Images were taken by a single investi- gator (IC) and assessed by two investigators blinded to the participants’ status (RAM and MT). Five images/participant were examined and nerve fibre density (number of nerve fibres per mm 2 of corneal tissue), nerve branch density (number of branches from major nerve trunks per mm 2 of corneal tissue), nerve fibre length (length of all nerve fibres per mm 2 of corneal tissue) and nerve fibre tortuosity were quantified [5]. The time to perform the examination was recorded and a tolerability questionnaire was administered by the research assistant. For those with diabetes, the average HbA 1c from the preceding year, duration of diabetes and BMI z-score were extracted from the clinical chart. HbA 1c was measured using the DCA 2000 immunoassay [normal range 20–42 mmol/mol (4–6%); Siemens Healthcare Diagnostics, Deerfield, IL, USA). The data are expressed as mean Æ SD and mean with 95% CI where appropriate. Non-parametric tests were used to describe differences between the groups. Eighteen children participated in this study, six children without diabetes, six with Type 1 diabetes and six with Type 2 diabetes. Participant characteristics are presented in Table 1. Mean age did not differ between the groups. BMI z-score was significantly greater in children with Type 2 diabetes compared with Type 1 diabetes. A non-significant trend was seen for a higher HbA 1c over the preceding 12 months and for a shorter duration of diabetes in partic- ipants with Type 2 diabetes compared with Type 1 diabetes. No child reported that corneal confocal microscopy was uncomfortable, although one found it difficult to sit still. One child had a minor vaso-vagal episode at the end of the examination. All participants stated that they would have the test performed again. Mean duration of the exam was 5.4 min (range 4.0–7.75 min) (Table 1). There was no significant difference between control subjects and those with Type 1 or Type 2 diabetes for nerve fibre density, nerve branch density, nerve fibre length or nerve fibre tortuosity (Table 1). This pilot study demonstrated that corneal confocal microscopy is a rapid, non-invasive and well-tolerated technique that may prove to be useful for the assessment of early neuropathy in children. Detection of diabetic neurop- athy at its earliest stages is important as improvement in risk factors (glycaemic control, blood pressure and lipids) may slow or prevent its progression [7] and/or promote nerve regeneration [8]. Current tests of neuropathy have principally been evaluated in adults and are not readily deployed in the paediatric population because of discomfort (neurophysiol- ogy), limited sensitivity (neurological exam and quantitative sensory testing) or invasiveness (punch skin biopsy). Given our findings, further study to assess the concurrent and predictive validity of corneal confocal microscopy for the detection of preclinical neuropathy in children and youth with diabetes is warranted. Funding sources None. Competing interests None declared. 630 ª 2012 The Authors. Diabetic Medicine ª 2012 Diabetes UK DIABETICMedicine Letters