From the Guidelines
Pupil reflex sympathetic loss, also known as Horner's syndrome, should be evaluated with a comprehensive eye examination and neuroimaging, including MRI with gadolinium and magnetic resonance angiography (MRA) or computed tomography angiography (CTA), to rule out a compressive lesion, especially an aneurysm involving the posterior communicating artery, as recommended by the American Academy of Ophthalmology in their 2020 Adult Strabismus Preferred Practice Pattern 1.
When a patient presents with pupil reflex sympathetic loss, a detailed medical and ocular history should be taken, including specific questions about patient symptoms, speed of onset of the strabismus, and possible associated unilateral or bilateral ptosis or other neurologic symptoms, such as ataxia, tremor, hemiplegia, sixth nerve or fourth nerve palsy, and noted pupillary asymmetry, and vision loss 1. Key characteristics to evaluate include whether the pupil is involved and the extent of the motility disorder and ptosis, as these factors can help determine the etiology of the third nerve palsy, with pupil-sparing third nerve palsy typically being secondary to microvascular disease, and pupil-involving third nerve palsy being more concerning for a compressive lesion 1. Some important considerations in the evaluation of pupil reflex sympathetic loss include:
- A comprehensive eye examination with particular attention to sensorimotor exam, evidence of ptosis and anisocoria, and pupillary responses in bright and dim illumination 1
- Neuroimaging, including MRI with gadolinium and MRA or CTA, to rule out a compressive lesion, especially an aneurysm involving the posterior communicating artery 1
- Active force generation testing in the office to identify muscles with residual function vs. completely paretic muscles 1
- Serologic testing for infectious diseases, such as syphilis and Lyme, and consideration of lumbar puncture if neuroimaging is normal 1
From the FDA Drug Label
Hydroxyamphetamine hydrobromide is an indirectly-acting sympathomimetic agent which, when applied topically to the eye, causes the release of endogenous norepinephrine from intact adrenergic nerve terminals resulting in mydriasis Since hydroxyamphetamine hydrobromide has little or no direct activity on the receptor site, dilation does not usually occur if there is damage to the presynaptic nerve terminal, e.g., Horner's Syndrome. However, it is not known whether damage to the presynaptic nerve terminal will influence the extent of mydriasis produced by PAREMYD® The loss of pupil reflex due to sympathetic loss (e.g. Horner's Syndrome) may affect the mydriatic effect of hydroxyamphetamine, as it relies on intact adrenergic nerve terminals to release endogenous norepinephrine.
- The drug may not be effective in producing mydriasis if there is damage to the presynaptic nerve terminal.
- However, the extent of mydriasis produced by PAREMYD® in cases of sympathetic loss is unknown 2.
From the Research
Pupil Reflex Sympathetic Loss
Pupil reflex sympathetic loss is associated with Horner's syndrome, a condition characterized by:
- Meiosis (pupil constriction)
- Ptosis (drooping eyelid)
- Facial anhydrosis (reduced sweating on the face) 3, 4, 5 This condition results from an interruption of the oculosympathetic pathway, which can be caused by various factors, including benign conditions like cluster headaches or life-threatening conditions like lung malignancy 3.
Clinical Presentation
Patients with Horner's syndrome typically present with a slightly droopy upper lid and a smaller pupil on the affected side, with or without a deficiency of sweating over the brow or face on the affected side 4, 5. The syndrome does not usually cause vision problems or other significant symptoms but is important as a warning sign that the oculosympathetic pathway has been interrupted, potentially indicating serious underlying pathology.
Diagnosis and Evaluation
Pharmacologic testing, such as cocaine eyedrop testing, can confirm the presence of Horner's syndrome and direct further testing and management 5, 6. Imaging studies, such as MRI, may be necessary to identify the underlying cause of the syndrome, particularly in cases with acute symptoms or pain 6. The yield of imaging studies varies depending on the localization of the lesion, with postganglionic lesions having a lower imaging yield than preganglionic lesions 6.
Pupil Assessment
Pupil assessment is an essential part of the evaluation of optic nerve disorders, including Horner's syndrome 7. The swinging flashlight test is a standard clinical tool for detecting pupillomotor asymmetry, while measurement of the pupil cycle time and infrared video pupillography can provide additional information on pupil function 7. However, the relationship between pupil measurements and electrodiagnostic tests is not well understood, and further research is needed to fully elucidate the value of pupil assessment in diagnosing and managing Horner's syndrome.