Light-near dissociation (LND) is a pupillary sign in which the pupillary light reflex is impaired while the near reflex (convergence, accommodation, miosis) is preserved.
LND has significant clinical importance. Since both the light reflex and near reflex share the efferent pathway (oculomotor nerve → ciliary ganglion → short ciliary nerves → sphincter pupillae), the mechanisms causing dissociation are limited, providing important clues for lesion localization.
Representative causative diseases include Parinaud syndrome, Argyll Robertson pupil, and tonic pupil (Adie syndrome). LND can occur unilaterally or bilaterally.
The incidence of Holmes-Adie syndrome (tonic pupil + areflexia) is 4.7 per 100,000, prevalence 2 per 1,000 per year, more common in women (2.6:1), and 80% are unilateral. 2)
It can occur unilaterally or bilaterally. Unilateral cases are often due to afferent pathway disorders or lesions of the ciliary ganglion/postganglionic nerves (e.g., Adie tonic pupil). Bilateral cases are caused by bilateral afferent lesions or midbrain dorsal lesions (Parinaud syndrome, Argyll Robertson pupil).
LND itself is often asymptomatic, with symptoms of the underlying disease being more prominent.
As a specific example, a 62-year-old man (with hypertension and diabetes) developed Parinaud syndrome due to hypertensive microangiopathy in the thalamus and putamen, presenting with upward gaze palsy, convergence-retraction nystagmus, and LND. 1) Also, a 34-year-old woman had a right pupil of 5 mm (left 4 mm), sluggish light reflex and vermiform movement of the right pupil, with normal near reflex in both eyes, diagnosed with Holmes-Adie syndrome. 2)
It refers to the characteristic that constriction to near stimulation occurs slowly, and after looking at a distance, the pupil remains constricted for a while and returns to its original size only slowly. “Tonic” is understood as “slowly reacting.” This tonicity is most easily observed during dilation after convergence.
The causes of LND are classified into three categories based on the lesion site.
Afferent Pathway Disorder
Definition: Lesions of the retinal ganglion cells, optic nerve, optic chiasm, optic tract, or lateral geniculate body.
Mechanism: The input for the light reflex is blocked, but the near response is preserved because it enters the Edinger-Westphal nucleus from the ventral side.
Features: Occurs unilaterally or bilaterally. If asymmetric, it is accompanied by RAPD.
Midbrain Dorsal Lesion
Definition: Lesions in the pretectal area or near the posterior commissure.
Representative diseases: Parinaud syndrome (pineal tumor is famous but actually rare; microvascular disorders, demyelination, and inflammation are more common) 1), Argyll Robertson pupil (in recent years, often associated with diabetes, cerebrovascular disorders, or demyelination).
Features: Causes bilateral LND.
Efferent Pathway Disorder + Aberrant Regeneration
Definition: Damage to the ciliary ganglion or postganglionic nerve followed by aberrant regeneration.
Representative disease: Adie’s tonic pupil (mostly idiopathic; also herpes zoster, encephalitis, neurosyphilis, diabetes, collagen disease, etc.).
Associated syndromes: Adie syndrome (tonic pupil + tendon reflex abnormalities), Ross syndrome (+ orthostatic hypotension and anhidrosis).
In a study of 40 cases of Parinaud syndrome by Shields et al. (1991–2016), 7.5% presented with ataxia as the main complaint. 3)
Traditionally, it was associated with neurosyphilis (tabes dorsalis), but in recent years it is more often associated with diabetes, cerebrovascular disease, and demyelination. When not accompanied by miosis, it is called “pseudo Argyll Robertson pupil” and is treated as a concept similar to tectal pupil.
In diagnosing LND, first determine laterality (unilateral or bilateral). This is because central causes are likely to be bilateral.
In the case reported by Vimisha et al., significant constriction of the right pupil was confirmed with 0.125% pilocarpine eye drops, leading to a definitive diagnosis of Holmes-Adie syndrome. 2)
The differential points for each condition are shown below.
| Finding | Adie’s tonic pupil | Argyll Robertson pupil | Tectal pupil (Parinaud) |
|---|---|---|---|
| Laterality | Unilateral (80%) | Bilateral | Bilateral |
| Resting pupil diameter | Moderate dilation | Extreme constriction | Moderate dilation |
| Tonicity | Present | Absent | Absent |
| Pilocarpine supersensitivity | Present | Absent | Absent |
It does not provide a basis for definitive diagnosis. Denervation supersensitivity occurs more easily in the periphery (distal to the ciliary ganglion) but can also appear centrally, so this test is positioned only as an auxiliary diagnostic tool. A comprehensive judgment should be made in combination with typical clinical findings (vermicular movements, segmental palsy, tonicity of the near reflex).
There is no direct treatment for LND itself. Treatment of the underlying disease is fundamental.
The pathway of the light reflex is as follows: retinal photoreceptors (cones and rods) → retinal ganglion cells (W cells) → optic nerve → optic chiasm → branches from the optic tract just before the lateral geniculate body → pretectal area of the midbrain → synapse → ipsilateral (and some contralateral via the posterior commissure) Edinger-Westphal (EW) nucleus → oculomotor nerve → cavernous sinus and superior orbital fissure → ciliary ganglion → short ciliary nerves → pupillary sphincter muscle.
In humans, the ratio of crossed to uncrossed fibers is approximately 1:1, and the strengths of the direct and consensual light reflexes are nearly equal.
The efferent pathway of the near reflex is shared with the light reflex, but the supranuclear fibers to the Edinger-Westphal nucleus for the near reflex run more ventrally than the midbrain pretectal area and posterior commissure through which the afferent fibers of the light reflex pass. Therefore, a lesion in the pretectal area causes dissociation between the light reflex and the near reflex.
95% of the parasympathetic fibers from the Edinger-Westphal nucleus go to the ciliary muscle, which controls accommodation, and 5% go to the sphincter pupillae muscle. Additionally, the ratio of neurons involved in the light reflex to those involved in the accommodation response in the ciliary ganglion is 3:97, so even if the light reflex is impaired, pupillary constriction during the near reflex is likely to be preserved.
This ratio is very important for the pathogenesis of light-near dissociation (LND).
Summarized in the table below.
| Mechanism | Responsible site | Representative diseases |
|---|---|---|
| Afferent pathway disorder | Retina to lateral geniculate body | Optic neuritis, retinal diseases |
| Dorsal midbrain lesion | Pretectal area, posterior commissure | Parinaud syndrome, Argyll Robertson pupil |
| Efferent pathway damage + aberrant regeneration | Ciliary ganglion / postganglionic nerve | Adie tonic pupil |
Details of efferent pathway damage and aberrant regeneration: After injury to the ciliary ganglion or postganglionic nerve, fibers that previously innervated the iris (sphincter pupillae) may aberrantly regenerate to the ciliary muscle. As a result, the light reflex remains poor, but the near response recovers. This is due to the ratio of fibers from the Edinger-Westphal nucleus: 95% to the ciliary muscle and 5% to the sphincter pupillae.
Mechanism of Argyll Robertson pupil: The responsible lesion is in the pretectal area of the dorsal midbrain. The light reflex pathway is impaired, but the ventral near response is preserved. Additionally, supranuclear inhibition to the Edinger-Westphal nucleus is also disrupted, leading to a tendency for miosis due to excitation of the Edinger-Westphal nucleus.
In recent years, the existence of intrinsically photosensitive retinal ganglion cells containing melanopsin as a photopigment has been clarified. These cells elicit the pupillary light reflex without involving photoreceptors, and strong short-wavelength blue light stimulation (around 470 nm) induces a slow, sustained miosis. They are primarily involved in regulating circadian rhythms, but also participate in the control of the pupillary light reflex, and further detailed elucidation is awaited.
Magdum & Aher (2024) reported a case of a 62-year-old man with hypertension and diabetes in whom hypertensive microbleeds in the thalamus and putamen caused Parinaud syndrome. 1) Traditionally, Parinaud syndrome is well-known to be caused by pineal tumors, but this case shows that it can actually be caused by microvascular disease such as hypertension and diabetes. MRI can detect microbleeds even with normal fundus findings. If the triad of upward gaze palsy, convergence-retraction nystagmus, and LND is present with abnormal gait, neurological evaluation should not be neglected.
Vimisha et al. (2024) reported a case of a 34-year-old woman with Holmes-Adie syndrome complicated by iron deficiency anemia, vitamin D3 deficiency, right knee arthritis, and patellar chondromalacia. 2) They discussed the association between rheumatoid arthritis/polycystic ovary syndrome and autonomic dysfunction, as well as the association between endometriosis and tonic pupil, showing that Adie syndrome can be accompanied by various systemic complications. In the usual course, Adie syndrome is not progressive and has a good prognosis, but if additional abnormal findings are observed, systemic evaluation is necessary.
