Petropoulos Ioannis N, Ferdousi Maryam, Marshall Andrew, Alam Uazman, Ponirakis Georgios, Azmi Shazli, Fadavi Hassan, Efron Nathan, Tavakoli Mitra, Malik Rayaz A
Division of Medicine, Weill Cornell Medical College-Qatar, Qatar Foundation, Education City, Doha, Qatar 2Centre for Endocrinology and Diabetes, University of Manchester and Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centr.
Centre for Endocrinology and Diabetes, University of Manchester and Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2498-504. doi: 10.1167/iovs.14-15919.
In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea.
A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified.
Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76.
The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.
体内角膜共焦显微镜检查(CCM)在糖尿病性多发性神经病(DPN)研究中越来越多地被用作替代终点。然而,尚不清楚对中央角膜进行成像是否能为DPN提供最佳诊断效用。因此,我们比较了中央角膜和下涡神经形态,下涡是位于中央角膜下方和鼻侧更远端且神经支配密集的区域。
共有53例1型/2型糖尿病患者和15例年龄匹配的对照受试者接受了详细的神经病变症状(NPS)、缺陷(神经病变残疾评分[NDS])、定量感觉测试(振动觉阈值[VPT]、冷觉和温觉阈值[CT/WT]以及冷诱导和热诱导疼痛[CIP/HIP])和电生理学(腓肠神经和腓总神经传导速度[SSNCV/PMNCV]以及腓肠神经和腓总神经波幅[SSNA/PMNA])评估,以诊断患有(DPN +)和未患有(DPN -)神经病的患者。对中央角膜的角膜神经纤维密度(CNFD)和长度(CNFL)以及下涡长度(IWL)进行了量化。
将对照受试者与DPN - 和DPN + 患者进行比较,NDS(0对2.6±2.3对3.3±2.7,P <0.01)、VPT(V;5.4±3.0对10.6±10.3对17.7±11.8,P <0.01)、WT(°C;37.7±3.5对39.1±5.1对41.7±4.7,P <0.05)有显著增加,而SSNCV(m/s;50.2±5.4对48.4±5.0对39.5±10.6,P <0.05)、CNFD(纤维/mm²;37.8±4.9对29.7±7.7对27.1±9.9,P <0.01)、CNFL(mm/mm²;27.5±3.6对24.4±7.8对20.7±7.1,P <0.01)和IWL(mm/mm²;35.1±6.5对26.2±10.5对23.6±11.4,P <0.05)有显著降低。对于DPN的诊断,CNFD、CNFL和IWL的曲线下面积(AUC)分别为0.75、0.74和0.70,IWL - CNFD组合的AUC为0.76。
CNFD、CNFL和IWL参数在诊断DPN患者方面具有相当的能力。然而,IWL即使在无DPN的患者中也能检测到异常。将IWL与CNFD相结合可能会提高CCM的诊断性能。