To quantify interictal photophobia in migraine with and without aura using reflexive eye closure as an implicit measure of light sensitivity and to assess the contribution of melanopsin and cone signals to these responses.

Participants were screened to meet criteria for 1 of 3 groups: headache-free (HF) controls, migraine without aura (MO), and migraine with visual aura (MA). MO and MA participants were included if they endorsed ictal and interictal photophobia. Exclusion criteria included impaired vision, inability to collect usable pupillometry, and history of either head trauma or seizure. Participants viewed light pulses that selectively targeted melanopsin, the cones, or their combination during recording of orbicularis oculi EMG (OO-EMG) and blinking activity.

We studied 20 participants in each group. MA and MO groups reported increased visual discomfort to light stimuli (discomfort rating, 400% contrast, MA: 4.84 [95% confidence interval 0.33, 9.35]; MO: 5.23 [0.96, 9.50]) as compared to HF controls (2.71 [0, 6.47]). Time course analysis of OO-EMG and blinking activity demonstrated that reflexive eye closure was tightly coupled to the light pulses. The MA group had greater OO-EMG and blinking activity in response to these stimuli (EMG activity, 400% contrast: 42.9% [28.4, 57.4]; blink activity, 400% contrast: 11.2% [8.8, 13.6]) as compared to the MO (EMG activity, 400% contrast: 9.9% [5.8, 14.0]; blink activity, 400% contrast: 4.7% [3.5, 5.9]) and HF control (EMG activity, 400% contrast: 13.2% [7.1, 19.3]; blink activity, 400% contrast: 4.5% [3.1, 5.9]) groups.

Our findings suggest that the intrinsically photosensitive retinal ganglion cells (ipRGCs), which integrate melanopsin and cone signals, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Moreover, we find a dissociation between implicit and explicit measures of interictal photophobia depending on a history of visual aura in migraine. This implies distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which the amplification of ipRGC signals elicits implicit and explicit signs of visual discomfort.

使用反射性闭眼作为光敏感度的隐性测量，量化有和没有先兆的偏头痛发作间期畏光，并评估黑视蛋白和视锥细胞信号对这些反应的贡献。

对参与者进行筛选，以满足 3 组中的 1 组的标准：无头痛 (HF) 对照组、无先兆偏头痛 (MO) 和有视觉先兆偏头痛 (MA)。如果 MO 和 MA 参与者支持发作期和发作间期畏光，则包括在内。排除标准包括视力受损、无法收集可用的瞳孔测量以及头部外伤或癫痫病史。在记录眼轮匝肌 EMG (OO-EMG) 和眨眼活动期间，参与者观察了选择性靶向黑视蛋白、视锥细胞或其组合的光脉冲。

我们研究了每组的 20 名参与者。MA 和 MO 组报告与 HF 对照组相比，对光刺激的视觉不适增加（不适等级，400% 对比度，MA：4.84 [95% 置信区间 0.33，9.35]；MO：5.23 [0.96，9.50]）与 HF 对照组相比（2.71 [0 , 6.47])。OO-EMG 和眨眼活动的时间过程分析表明，反射性闭眼与光脉冲紧密耦合。与这些刺激相比，MA 组具有更大的 OO-EMG 和眨眼活动（EMG 活动，400% 对比度：42.9% [28.4, 57.4]；眨眼活动，400% 对比度：11.2% [8.8, 13.6]） MO（EMG 活动，400% 对比度：9.9% [5.8, 14.0]；眨眼活动，400% 对比度：4.7% [3.5, 5.9]）和 HF 对照（EMG 活动，400% 对比度：13.2% [7.1, 19.3] ]；眨眼活动，400% 对比度：4.5% [3.1, 5.9]) 组。

我们的研究结果表明，整合黑视蛋白和视锥细胞信号的内在光敏视网膜神经节细胞 (ipRGCs) 为在畏光状态下光诱导的反射性闭眼提供了传入输入。此外，我们发现发作间期畏光的隐性和显性测量之间存在分离，这取决于偏头痛的视觉先兆病史。这意味着偏头痛形式存在不同的病理生理学，与单独的神经通路相互作用，ipRGC 信号的放大通过这些神经通路引起视觉不适的隐性和显性迹象。