This study examined changes in upper eyelid position after transitioning from photopic to scotopic conditions in patients with unilateral Horner syndrome. We found that upper eyelid retraction was diminished in the affected side compared to the contralateral, uninvolved eye.
We previously documented upper eyelid retraction synchronously with pupillary dilation following the transition from light to dark conditions in a cohort of healthy individuals.
7 This synchronicity led us to hypothesize that this reflex shares a common pathway with the “pupillary-light reflex” and that the Müller's muscle and its oculosympathetic innervation serve as the efferent arm. This phenomenon may be the mature form of the “eye-popping reflex” observed in infants initially described by Perez et al.
8 We also suggested a possible mechanism to explain the physiologic advantage of such a reflex. As the pupil dilates in the dark, the palpebral aperture needs to widen to avoid peripheral scotoma. However, based on these observations alone, we could not demonstrate the involvement of either the Müller's muscle or associated sympathetic pathways. Furthermore, we could not exclude the contribution of other upper eyelid retractors, such as the levator palpebrae superioris (LPS), frontalis, or brow muscles.
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The current study was designed to isolate the contribution of Müller's muscle to the upper eyelid retraction we observed following a transition from light to dark conditions. Müller's muscle consists of thin, smooth muscle fibers and is sympathetically innervated through the oculosympathetic pathway, whereas LPS is a striated muscle that receives motor innervation from the oculomotor nerve.
9–11 Although it is difficult to isolate the action of Müller's muscle in clinical practice, pharmacological testing, or direct measurements of eyelid function, in its absence, it may provide clinical information regarding the muscle's functional ability.
12,13 Phenylephrine, an alpha-adrenergic agonist, stimulates the sympathetically innervated Müller's muscle independent of levator function.
12,13 Alternatively, in patients with Horner syndrome, disruption of sympathetic innervation to Müller's muscle results in relatively mild ptosis with preserved LPS function.
3,4 Therefore, the current study was designed to compare the amplitude of the eyelid reflex between both upper eyelids: one with intact and one with disrupted sympathetic innervation. Overall, we found that the observed reflex was significantly diminished in the sympathetically denervated side compared to the unaffected, contralateral eye. This supports the role of the sympathetic nervous system and the Müller's muscle in this reflexive adjustment of the upper eyelid position.
Nevertheless, this calls for a renewed discussion on the nature of this reflex. The term “pupillary light reflex” describes the reflex arc that causes miosis in response to light as a result of parasympathetic stimulation.
1 Conversely, the “pupillary dark reflex” triggers mydriasis during the transition to scotopic conditions and involves a separate pathway of third-order oculosympathetic fibers that collectively innervate the dilator pupillae muscle.
7,14 This common sympathetic pathway also projects terminating fibers to Müller's muscle, resulting in sympathetically driven muscle contraction during dark conditions.
1,2 Therefore, the term “eyelid-dark reflex” seems more appropriate to describe the reflex we documented in both studies.
This study and its methodology may have some limitations. Patient imaging was performed in our institution's imaging suite, where only relative scotopic conditions could be achieved. Furthermore, despite identical conditions and instructions to patients, strict compliance of patients during imaging may have varied between subjects and, therefore, affected measurement accuracy. Additionally, Horner syndrome is a clinical diagnosis that may have different levels of sympathetic denervation, with some patients retaining partial function of their Müller's muscle. However, several aspects of our study's design and conclusions enhance our results' internal and external validity. In both groups, we found a significant change in pupil diameter when transitioning from light to dark conditions, validating an adequate change in lighting conditions. Furthermore, our measurements found significant ptosis and miosis in the eye affected by Horner syndrome compared with the unaffected side, confirming that clinically significant Horner syndrome was present at the time of imaging. Last, there were no significant differences in pupil diameter, margin-to-reflex distance 1, margin-to-reflex distance 2, or palpebral fissure height measurements when we compared the unaffected eyes with those of the healthy subjects reported in our previous study.
In conclusion, this study provides further evidence that the sympathetically innervated Müller's muscle serves as the efferent arm of a reflexive upper eyelid retraction in response to the transition from light to dark. We believe the term “eyelid-dark reflex” may describe this phenomenon more accurately. The clinical significance of this reflex remains to be elucidated, but warrants further investigations to better understand the function of the oculosympathetic chain. Furthermore, reduced eyelid retraction in patients with oculosympathetic disruption may assist in the clinical diagnosis of patients with suspected but unclear Horner syndrome.