A reflex is a general term for involuntary responses involved in protective and regulatory functions. Reflexes related to the eye are broadly classified into the following nine types.
Pupil diameter is determined by the balance between the sphincter pupillae (parasympathetic innervation) and the dilator pupillae (sympathetic innervation). Both muscles receive dual adrenergic and cholinergic innervation. In normal individuals, the pupil oscillates with a nearly constant rhythm in a bright room (hippus).
The main factors affecting pupil diameter are shown below.
| Factor | Notes |
|---|---|
| Age | Infants 2–2.5 mm, largest in late teens, tendency toward miosis in elderly |
| Individual variation | Normal range 2–6 mm, average about 4 mm indoors |
| Physiological anisocoria | 20% of normal individuals, a difference of about 0.5 mm is normal |
| Others | Refraction, accommodation, illumination, sound, color, diurnal variation, antihistamines, etc. |
In infants, the dilator muscle is underdeveloped, so the pupil is small, about 2–2.5 mm, and reaches its maximum size in the late teens. In the elderly, sympathetic nerve function declines, leading to a tendency toward miosis. Normal pupil diameter varies widely from 2 to 6 mm.
Subjective symptoms that occur when each reflex is abnormal are shown below.
The following are the major abnormal reflex findings that a physician checks during an examination.
RAPD
Definition: A condition in which the pupil dilates instead of constricts when light is shone during the swinging flashlight test (relative afferent pupillary defect).
Mechanism: Because the light stimulus to the affected eye reaches the brainstem with a weaker signal than that from the healthy eye, dilation occurs despite the light stimulus.
Representative diseases: Optic neuritis, traumatic optic neuropathy, extensive retinal diseases.
Light-Near Dissociation
Definition: A condition in which the light reflex is absent but the near reflex is preserved.
Mechanism: The ratio of neurons for the light reflex to those for the accommodation reflex in the ciliary ganglion is 3:97. 95% of EW nucleus parasympathetic fibers go to the ciliary muscle (accommodation), and only 5% go to the sphincter pupillae.
Representative diseases: Parinaud syndrome, Argyll Robertson pupil, Adie syndrome.
Dilation lag: A characteristic finding in Horner syndrome, where anisocoria at 5 seconds after lights off is greater than at 15 seconds. Normal pupils reach maximum dilation in 12–15 seconds, but pupils with dilation lag take up to 25 seconds. A difference in anisocoria >0.4 mm between 5-second and 15-second flash photographs is considered positive.
Pupillary escape: A phenomenon in which the pupil initially constricts under sustained light exposure and then redilates. It occurs on the side of retinal or optic nerve disease and is common in patients with central visual field defects.
Pontine miosis: When the ascending pathway from the paramedian pontine reticular formation that inhibits the Edinger-Westphal nucleus is damaged, the Edinger-Westphal nucleus becomes abnormally excited, resulting in severe miosis with a pupil diameter of about 1 mm. The light reflex and near reflex are preserved.
In dysthyroid optic neuropathy (DON), there are cases where RAPD is positive even when visual acuity is maintained at 6/6 (1.0). In the EUGOGO survey, RAPD was observed in 45% of confirmed DON cases, and best-corrected visual acuity (BCVA) of 20/40 or better was maintained in 50-70% of cases1). It is important to check RAPD in addition to visual acuity.
The representative causative diseases that cause each reflex abnormality are summarized.
Causes of RAPD (relative afferent pupillary defect):
Causes of light-near dissociation:
Causes of Horner syndrome: Due to impairment anywhere along the sympathetic pathway (hypothalamus → spinal cord T1-T3 → superior cervical ganglion → pupillary dilator muscle). Accompanied by mild ptosis, delayed dilation, and facial anhidrosis. Causes include head and neck diseases, mediastinal tumors, retrobulbar lesions, and congenital conditions.
Causes of abnormal corneal reflex: Trigeminal nerve lesions, unilateral eye disease (neurotrophic keratitis), orbicularis oculi weakness. Also occurs in posterior fossa diseases (acoustic neuroma, multiple sclerosis, Parkinson’s disease, brainstem tumors, syringomyelia).
Causes of loss of Bell’s phenomenon: In supranuclear palsy (Steele-Richardson syndrome, Parinaud syndrome, double elevator palsy), voluntary elevation is impossible but Bell’s phenomenon is often preserved. It is lost in thyroid eye disease (restrictive inferior rectus), myasthenia gravis, and orbital floor blowout fractures.
Perform the test in a slightly dim room (semi-dark room), and shine the light from the same angle (front) for both eyes. Illuminating from an oblique or superior angle can cause differences between direct and indirect light, leading to misjudgment. Shine the light on each eye for 2–3 seconds and observe the pupillary response (constriction or dilation) when the light is applied.
Turn off the lights in a bright room and observe both pupils in dim light. Compare flash photographs taken 5 seconds and 15 seconds after turning off the lights; if the anisocoria difference exceeds 0.4 mm, it is considered positive for Horner syndrome. Infrared videography has the highest sensitivity.
The corneal reflex is used to assess trigeminal nerve sensation in patients with clouded consciousness or semicoma. For the convergence reaction, a fixation target is brought close to the eyes to confirm the miosis phase, then the patient looks into the distance to confirm the mydriasis phase as the pupils quickly return.
Treatment of each reflex abnormality is based on addressing the underlying disease.
Afferent pathway: Retinal photoreceptors (W cells) → Retinal ganglion cells → Optic nerve → Optic chiasm → Optic tract → Branches off from the visual pathway before the lateral geniculate nucleus → Midbrain pretectal area (olivary pretectal nucleus)
Projections from the pretectal area: Some fibers project to the ipsilateral Edinger-Westphal (EW) nucleus, and some cross via the posterior commissure to the contralateral EW nucleus. In humans, the crossed-to-uncrossed ratio is approximately 1:1.
Efferent pathway: EW nucleus (preganglionic parasympathetic neurons) → Oculomotor nerve → Cavernous sinus and superior orbital fissure → Ciliary ganglion (synapse) → Short ciliary nerves → Pupillary sphincter muscle (M3 muscarinic receptors)
95% of parasympathetic fibers from the EW nucleus innervate the ciliary muscle (accommodation), and only 5% go to the pupillary sphincter. This ratio is directly linked to the mechanism of light-near dissociation. The latency of the pupillary light reflex is approximately 200 milliseconds with a sufficiently bright stimulus. Macular stimulation is most effective, and the response diminishes toward the periphery.
Afferent pathway: Retina → Optic tract → Lateral geniculate body → Visual cortex
The supranuclear fibers to the Edinger-Westphal nucleus for the near reflex run ventral to the pretectal area and posterior commissure, through which the afferent fibers of the pupillary light reflex pass. Therefore, in pretectal area lesions, only the light reflex is impaired while the near reflex is preserved (light-near dissociation).
The efferent pathway (miosis) is shared with the light reflex. The efferent pathway (accommodation) follows: Edinger-Westphal nucleus → Oculomotor nerve → Ciliary ganglion → Short ciliary nerves → Contraction of ciliary muscle → Relaxation of zonular fibers → Increase in lens refractive power.
In addition to the classical visual system mediated by cones and rods, intrinsically photosensitive retinal ganglion cells (ipRGCs) containing melanopsin as a photopigment have been identified. They produce a slow, sustained pupillary constriction in response to strong short-wavelength blue light stimulation (near 470 nm). They are primarily involved in regulating circadian rhythms and also contribute to the pupillary light reflex control mechanism.
Age-related lens opacification and senile miosis reduce the amount of short-wavelength light reaching the retina. This decreases ipRGC stimulation and may also affect the pupillary light reflex4). Meanwhile, melanopsin function remains relatively stable from childhood to the 80s, showing greater resilience than age-related declines in rod and cone density4).
Pupillary Light Reflex (Classical Pathway)
Photoreception: Light sensitivity via cones and rods.
Characteristics: Short latency, fast contraction speed, rapid redilation.
Application: Detection of optic nerve and retinal diseases (RAPD).
PLR (Melanopsin Pathway)
Photoreception: Blue light sensitivity (470 nm) by ipRGCs.
Characteristics: Long latency, slow contraction speed, sustained response.
Applications: Circadian rhythm regulation, biomarker research for neurological diseases.
95% of parasympathetic fibers to the Edinger-Westphal nucleus go to the ciliary muscle (accommodation), and only 5% go to the sphincter pupillae. The ratio of neurons in the ciliary ganglion involved in the pupillary light reflex and accommodation is 3:97. Furthermore, the supranuclear fibers for the near response run more ventrally than the pretectal area, so lesions in the pretectal area only impair the pupillary light reflex.
A systematic review and meta-analysis by Dawidziuk et al. (2025) including 11 studies showed significant abnormalities in PD patients: effect size -0.92 (p<0.01) for maximum constriction velocity (VMax), -0.58 (p<0.05) for constriction amplitude (CAmp), and 0.46 (p<0.05) for constriction latency (CL) in the pupillary light reflex3). PLR may be a promising biomarker for early PD detection.
PD patients may also be affected in ipRGC, and wavelength-specific PLR measurement may help distinguish PD patients from healthy individuals3).
In patients undergoing targeted temperature management (TTM) after cardiac arrest, a higher %PLR measured within 0–24 hours of admission was significantly associated with favorable neurological outcomes at 3 months (SMD 0.87; 95% CI 0.70–1.05; I²=0%) 5). However, the quality of evidence is low.
A meta-analysis by Feng et al. (2025) of 12 studies involving 1530 patients showed that qPLR (OR 24.50; 95% CI 13.08–45.86) had higher predictive accuracy for neurological prognosis than NPI (neurological pupil index; OR 15.55; 95% CI 7.92–30.55) (AUC 0.89 for qPLR vs. 0.66 for NPI) 6).
The existence of compensatory mechanisms with aging has also been suggested. Adaptation to long-term light environments may preserve non-visual photosensitivity 4). Changes in melanopsin function from childhood to older age have been confirmed to be more gradual than changes in rod and cone density 4).
