In the absence of any deformities of the iris or eyeball proper, anisocoria is usually the result of a defect in efferent nervous pathways controlling the pupil traveling in the oculomotor nerve (parasympathetic fibers) or the sympathetic pathways. Physical lesions and drugs causing anisocoria will do so via disruption of these pathways.
Clinically, it is important to establish which of the two pupils is behaving abnormally.
If the smaller of the two pupils is the abnormal one, dimming the ambient light will not cause it to dilate, in which case a defect in sympathetic fibers is suspected, as seen in Horner's syndrome.
Alternatively, if the abnormal pupil is the larger one, it will fail to contract in response to light, raising suspicion for a parasympathetic nerve defect, possibly an oculomotor nerve palsy.
A relative afferent pupillary defect or RAPD also known as a Marcus Gunn pupil does not cause anisocoria.
When anisocoria occurs and the examiner is unsure whether the abnormal pupil is the constricted or dilated one, if a one-sided ptosis is present then the abnormally sized pupil can be presumed to be the one on the side of the ptosis.