Kinard Krista I, Smith A Gordon, Singleton J Robinson, Lessard Margaret K, Katz Bradley J, Warner Judith E A, Crum Alison V, Mifflin Mark D, Brennan Kevin C, Digre Kathleen B
Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
Headache. 2015 Apr;55(4):543-9. doi: 10.1111/head.12547. Epub 2015 Mar 31.
We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy.
For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire.
A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome.
We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations.
我们采用体内角膜共焦显微镜检查，研究慢性偏头痛患者与正常人群角膜基底神经丛的结构差异。我们使用经过验证的问卷和泪液功能测试，确定同一组慢性偏头痛患者中干眼症的患病率。三叉神经系统的激活与偏头痛有关。角膜伤害性感觉由三叉神经轴突介导，这些轴突在半月神经节和脑干中形成突触，并发挥伤害性、保护性和营养性功能。利用体内角膜共焦显微镜可以对角膜基底神经丛进行无创成像。
在这项病例对照研究中，我们招募了慢性偏头痛患者，并将他们与性别和年龄匹配的对照组进行比较。排除患有已知与周围神经病变相关疾病的患者、周围神经病变患者或既往有角膜或眼内手术史的患者。参与者使用配备罗斯托克角膜模块的海德堡视网膜断层扫描III共焦显微镜进行体内角膜共焦显微镜检查。采用既定方法测量神经纤维长度、神经分支密度、神经纤维密度和迂曲系数。偏头痛参与者接受了用丙美卡因测试基础泪液分泌、用棉棒评估角膜敏感性、测量泪膜破裂时间，并完成一份经过验证的干眼问卷。
共有19名慢性偏头痛患者和30名对照参与者完成了研究。年龄和性别方面无显著差异。与对照组相比，偏头痛患者的神经纤维密度显著降低（48.4±23.5对71.0±15.0根/平方毫米，P<.001）。与对照组相比，慢性偏头痛组的神经纤维长度有所减少，但差异无统计学意义（21.5±11.8对26.8±5.9毫米/平方毫米，P<.084）。两组的神经分支密度相似（114.0±92.4对118.1±55.9分支/平方毫米，P<.864）。慢性偏头痛组和对照组的迂曲系数和对数迂曲系数也相似。所有偏头痛受试者都有与干眼综合征诊断相符的症状。
我们发现，在本研究使用的样本中，伤害性角膜轴突存在结构变化，这进一步支持了三叉神经系统在偏头痛发病机制中起关键作用的假说。体内角膜共焦显微镜有望成为未来偏头痛研究以及检查角膜神经支配改变研究的生物标志物。干眼症状在该人群中似乎极为普遍。偏头痛、角膜神经结构和干眼之间的相互关系将是未来研究的主题。
