Interactive Effects of Obstructive Sleep Apnea and Type 2 Diabetes Mellitus on Corneal Nerves: Preliminary Findings

Abstract

INTRODUCTION: In vivo corneal confocal microscopy (IVCM) is increasingly being used to evaluate the corneal subbasal nerve plexus (SBNP) in patients with Type 2 Diabetes Mellitus (T2DM). Current data suggests that loss of the SBNP is a surrogate marker for peripheral diabetic neuropathy (DPN). Obstructive Sleep Apnea (OSA) is an under diagnosed condition that is highly prevalent in patients with T2DM. The purpose of this study is to examine the impact of OSA on SBNP changes in patients with T2DM. METHODS: A total of 184 patients will be recruited across four groups: A) T2DM and OSA, 2) OSA, 3) T2DM, and 4) healthy controls. A physician diagnosis of T2DM and/or OSA is required for inclusion in each study group. Groups are matched for sex, age, and obesity status. Each patient undergoes testing for the following: serology for Hemoglobin A1c and high sensitivity C-reactive protein, an eye exam with dry eye testing and dilated fundus examination, anthropometric measurements, tear collection, IVCM, measurement of corneal sensitivity, and optical coherence tomography to assess the retinal nerve fiber layer (rNFL) and macula. Patients are also asked to complete three questionnaires including the Stop-Bang questionnaire (to assess risk of OSA), the ocular surface disease index questionnaire (to assess dry eye disease), and a CPAP compliance survey. IVCM images are analyzed for determination of nerve fiber length and density, tortuosity (short term and long term), and basal corneal epithelial cell and dendritic cell density. Human tears are analyzed for tear levels of IGFBP3 using ELISA and extracellular tear DNA is quantified using a Qubit Fluorometer. Anthropometric measurements are used to calculate body mass index and waist to height ratio. RESULTS: Preliminary data confirms that Hemoglobin A1c is highest in the two groups with T2DM patients; STOP BANG scores and male neck circumference are highest in the two groups with OSA. Nerve fiber length is shortest in patients with T2DM. Tortuosity and morphological differences have been found amongst the four groups. A slight decrease has been found in the rNFL for patients with OSA and T2DM. DISCUSSION: A recent study in the UK analyzed the risk and severity of DPN in patients with OSA. Among 266 patients with T2DM, those with OSA had a higher prevalence of DPN and the severity of neuropathy was related to the severity of OSA and not the duration of T2DM. The results of the present study will be the first to show a definitive relationship in changes in the SBNP and rNFL between patients with OSA and T2DM.