Differential Diagnosis
Common Physical Signs in Pupil

Relative afferent pupillary defect
(RAPD, also known as Marcus-Gunn pupil. It is caused by unequal light conduction of the afferent visual pathway. It is best examined in the dim light with distant fixation. The lesion can be anywhere from the retina to the optic tract before the lateral geniculate body. In the clinical examination, the most common case would be optic nerve lesion due to either optic neuritis or ischaemic causes)

Retina lesions
(usually extensive resulting in loss of large number of ganglion cells)

  • vascular causes (central retinal artery or vein occlusion)
  • advanced glaucoma
  • infective (extensive chorioretinitis as in toxoplasmosis, retinitis such as cytomegalovirus infection or acute retinal necrosis)
  • total retinal detachment
  • Optic nerve lesions
  • optic neuritis
  • ischaemic optic neuropathy (non-arteritic or arteritic due to giant cell arteritis)
  • tumours (primary such as glioma and  meningioma or secondary)
  • trauma (traumatic optic neuropathy or optic nerve avulsion)
  • congenital (unilateral optic nerve hypoplasia)
  • Chiasmal lesions
    (this can cause more damage to one optic nerve than the other resulting in RAPD)
    tumours (primary such as pituitary tumours and craniopharyngioma or secondary from metastasis)
  • vascular lesions (internal carotid artery aneurysm)
  • inflammatory (granuloma such as sarcoidosis and TB or idiopathic such as Tolosa-Hunt syndrome)
  • Optic tract lesions
    (RAPD occurs if more visual field in one eye is affected more than the other)
  • vascular lesions (ischaemic or haemorrhagic stroke)
  • tumours (primary such as meningioma and astrocytoma or secondary)
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    (The most common cases in the clinical examination are Horner's syndrome, Adie's pupil and third nerve palsy. The first step in your examination is to determine which is the abnormal eye and this is helped greatly by the associated sign especially ptosis. In less obvious cases, the increase in anisocoria in bright light suggest the large pupil to be abnormal whereas such increase in dim light suggest the small pupil to be abnormal)

    Abnormal small pupil

  • congenital (essential)
  • Horner's syndrome
  • drug-induced (parasympathomimetic)
  • previous uveitis resulting in posterior synechiae
  • traumatic miosis
  • Abnormal large pupil
  • congenital (essential)
  • Adie's pupil
  • third nerve palsy
  • damage to the iris (traumatic or inflammation)
  • drug-induced (anticholinergic blockage or adrenergic stimulation)
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    Light-near dissociation
    ( The condition occurs when the near response is stronger than the light response. It is true to say that all light-near dissociation is due to abnormal light response with sparing of the near response. The commonest case in clinical examination is Adie's pupil.
    As the light response has an afferent and efferent pathway, the lesions can be thus classified)

    Lesions of the afferent pathway

  • lesions in the retina (occurs when both eyes are blind as in diabetic retinopathy resulting in absent light response)
  • lesions in the optic nerves (if both optic nerves are damaged as in giant cell arteritis)
  • lesions in the  midbrain  (lesion involving the pretectal region, the classical one being Parinaud's syndrome from pinealoma)
  • lesions in the Edinger-Westphal nucleus (classical one being Argyll-Robertson's pupil)
  • Lesions of the efferent pathway
    (this is usually caused by aberrant regeneration of the damaged nerve resulting in better near reaction)
  • lesions in the third nerve
  • lesions in the ciliary ganglion (typified by Adie's pupil)
  • other peripheral neuropathies for example Charcot-Marie-Tooth syndrome, amyloidosis, alcoholism and diabetes can also cause light-near dissociation and are probably due to regeneration of damaged nerves
  • Other cause of unknown aetiology
    • myotonic dystrophy
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