As an ancillary test to determine the cause of changes in the size of the pupils, the functional integrity of the sympathetic and parasympathetic nerve endings in the iris may be determined by the use of certain drugs detailed in the next section. Atropinics dilate the pupils by paralyzing the parasympathetic nerve endings; physostigmine and pilocarpine constrict the pupils, the former by inhibiting cholinesterase activity at the neuromuscular junction and the latter by direct stimulation of the sphincter muscle of the iris. Epinephrine and phenylephrine dilate the pupils by direct stimulation of the dilator muscle. Morphine and other narcotics act centrally to constrict the pupils.
In an eye with intact sympathetic innervation, cocaine dilates the pupils by preventing the reabsorption of norepinephrine into the nerve endings. With Horner syndrome, the normal pupil will dilate but the miotic pupil will remain small, and a difference in size of 0.8mm or greater is considered diagnostic (Kardon). More recently, apraclonidine, a weak direct alpha-agonist drug has been shown to reliably reverse the anisocoria of Horner syndrome and has become the preferred drug for testing. Normally apraclonidine does not exert significant dilatory effect, but with denervation hypersensitivity that accompanies Horner syndrome, the miotic pupil dilates in response to the drug. One drop (0.5 percent solution) is placed in each eye, the eyes are kept closed for 1 min and the drops are repeated 5 min later. Enlargement of the miosis with the affected pupil becoming larger than the unaffected one 30 to 45 min after instillation is definite evidence of a Horner syndrome. Ptosis is also reduced, sometimes to a remarkable extent. It was originally developed as a treatment for glaucoma (Koc et al).
In diabetes mellitus, where autonomic spinal and cranial nerves are often involved, the pupils are affected in the majority of cases. They are smaller than would be expected for age because of involvement of pupillodilator sympathetic fibers, and mydriasis may be excessive upon instillation of sympathomimetic drugs. The light reflex, mediated by parasympathetic fibers is also reduced, usually to a greater degree than constriction on accommodation (Smith and Smith, 1987). Some of these abnormalities require special methods for their demonstration.
In almost all the forms of late syphilis, particularly tabes dorsalis, the pupils are bilaterally small, irregular, and unequal; they fail to react to light, although they do constrict on accommodation (light-near dissociation) and do not dilate properly in response to mydriatic drugs. Atrophy of the iris is associated in some cases. This is known as the Argyll Robertson pupil. The exact locality of the lesion is not certain but it is generally believed to be in the tectum of the midbrain proximal to the oculomotor nuclei where the descending pupillodilator fibers are in close proximity to the light reflex fibers (Fig. 13-9). A similar pupillary abnormality has been observed in the meningoradiculitis of Lyme disease and in diabetes. A dissociation of the light reflex from the accommodation-convergence reaction is also part of the dorsal midbrain syndrome but miosis, irregularity of pupils, and failure to respond to a mydriatic are usually not present.