axons by way of the third cranial nerve to the ipsilateral ciliary ganglion from where postganglionic parasympathetic fibers innervate the eye via the short posterior ciliary nerves, terminating at the pupillary sphincter. This anatomically bilateral sharing of neural input has the important consequence that damage to the afferent visual pathways that lead to the Edinger-Westphal nucleus cannot cause an anisocoria. Thus, anisocoria is never a sign of an afferent disturbance, but is always a sign of an efferent pupillary disorder. This is the physiologic foundation for the tests to be described in the following sections of this chapter.

What Is Needed For Pupillary Testing?

Pupillary testing requires two bright lights (e.g., an indirect ophthalmoscope and a bright flashlight), a pocket gauge for measuring pupillary diameters, neutral density filters, a slit lamp, a topical solution of 5% cocaine, occasionally a 1% solution of hydroxyamphetamine (where available), pilocarpine 0.1% and 1.0%, and phenylephrine 2.5% eye drops.

J Pearl

For presbyopic examiners, a generous near correction is needed for adequate study of pupillary sizes, shapes, and movements. Pupillary examinations are usually best done in a dimly illuminated, nearly dark room (see below), which makes proper correction of the examiner's refractive errors particularly important.

Systematic Examination of the Pupils

First step: Confirm that the pupils respond to light. Only in the dark can the pupils really show how well they can react, so be sure that the room light is as dim as convenience will allow. The patient should be asked to look into the distance, to limit intrusion by the miosis of the near reflex. Using a strong light source (such as an indirect ophthalmoscope) stimulate both eyes simultaneously. If both pupils visibly and symmetrically constrict, go to the second step.

If one or both pupils do not appear to react, a pathological state in need further examination has been found (go to the fourth step).

Second step: Compare the pupillary diameters to one another. Examination and interocular comparison of the pupillary diameters determines whether the autonomic (efferent) innervation of the eye is intact. If there is an anisocoria, repeat testing of both pupils' responses to a strong, binocular light stimulus.

| Pearl

These two steps can be combined. Illuminate both eyes from a position below the visual axis and then slowly bring the light source closer to the eyes. Determine whether the pupils are symmetrical in size and whether both constrict equally.

Third step: Do the swinging flashlight test. This step compares the afferent pupillary responses of one eye to the other. (The swinging flashlight test is described in detail in Chap. 2).

When a pupil is poorly reactive or does not react to a light stimulus, the swinging flashlight test cannot be done in the usual way since the test requires that both pupils react equally to light. Moreover, if there is an anisocoria, the requirements for this test are somewhat different. Experience has found that when there is an interocular difference of 0.5 mm or more in pupillary diameter, the test is best done by judging the movements of the pupil that has the better light reaction, comparing its direct and consensual responses. This method is more completely described in Chap. 2.

Anisocorias of 0.3 mm or less are not usually visible. If normal responses have been found up to this point, the test is concluded. It should be recorded as, "Pupils sizes and light responses are equal; there is no relative afferent pupillary defect."

Fourth step: Examination of pathological findings. After completion of the first three steps, the following pathological states are possible:

1. A relative afferent pupillary defect (RAPD)

2. An anisocoria with normal responses to light in both eyes

3. A monocular or bilateral deficit in light responses

Further Testing When Pupillary Signs Are Abnormal

Relative Afferent Pupillary Defect

When an RAPD is found, the cause must be identified. This process is described in some detail in Chap. 2. If the cause cannot be found, perimetric examination of both eyes is necessary.

Anisocoria with Bilaterally Normal Pupillary Reactions to Light

Dilation Test

The dilation test uses a comparison of the speed of pupillary dilation of both eyes after extinguishing a bright light stimulus. It determines whether there is evidence of a problem with sympathetic innervation of the pupil(s). A prob-

Right eye Left eye a b

Fig. 5.2. Typical responses of the pupils in the normal state and in the classical pupillary disorders during routine examination. a Testing of anisocoria and the pupillary light response. b Responses to the swinging flashlight test with normal afferent function. c Responses found in monocular disorders of the afferent portion of the reflex arc. 1 Inspection in the dark; 2 inspection with lights on: no anisocoria, and with either normal responses or signs of an

Fig. 5.2. Typical responses of the pupils in the normal state and in the classical pupillary disorders during routine examination. a Testing of anisocoria and the pupillary light response. b Responses to the swinging flashlight test with normal afferent function. c Responses found in monocular disorders of the afferent portion of the reflex arc. 1 Inspection in the dark; 2 inspection with lights on: no anisocoria, and with either normal responses or signs of an afferent defect; 3,4 light reactions for the interocular comparisons during the swinging flashlight test with normal responses and no relative afferent pupillary defect (RAPD); 5, 6 left RAPD; 7-12: pupillary light responses in the case of a widely dilated pupil in the right eye that does not respond to light; 9,10 no RAPD; 11,12 in the presence of an RAPD on the right

lem is that the test is done in a darkened room. Ideally, one should use an infrared video system to examine pupillary movements in the dark, i.e., after turning the light stimulus off. A practical alternative is to use a separate, weak light source to illuminate both eyes at a tangential angle from below, so that both pupils are visible and a minimum area of retina is being illuminated in each eye. It is best not to look at the eye with the brighter stimulus, since this causes light adaptation of the examiner's eyes, making it difficult to see the dimly illuminated pupil.

When the pupils dilate well and with no speed difference between them, the anisocoria is likely to be physiologic. Physiologic anisocoria of greater than 1 mm is very uncommon, so when the difference is greater than 1 mm, use of the cocaine test is necessary (see below). Also, when the smaller pupil dilates more poorly, the cocaine test is likewise indicated.


Observation of the pupils in the dark with infrared light is simpler and more effective than are examinations done under dimly illuminated conditions. Infrared video recording is now easy to implement. Video camcorders commonly have a "night" or "zero lux" setting, which is a form of infrared video recording. The barrier filter of the camera can be removed, and an infrared light source turned on. Such devices are reasonably inexpensive, making their use for pupillary testing very attractive.

Cocaine and Hydroxyamphetamine Tests

The cocaine test is indicated in three situations:

1. For anisocoria greater than 1 mm and normal pupillary light reactions

2. For slower dilation of the smaller pupil

3. For ptosis ipsilateral to the smaller pupil (suspected Horner's syndrome)

Cocaine retards the reuptake and inactivation of noradren-alin within the synaptic cleft. Thus, it is an indirect sympathomimetic. When sympathetic innervation is intact, there is a constant rate of release of noradrenalin into the synapse, and cocaine blocks its reuptake, causing an accumulation of the neurotransmitter, and resulting in pupillary dilation. If the anisocoria is physiologic, the smaller pupil dilates more than does the larger pupil, reducing the aniso-coria.

Drops of 5% cocaine are instilled in both eyes (all pharmacologic pupil testing should be done symmetrically, comparing one eye to the other). This preparation is usually available at hospital pharmacies. If there is any uncertainty about the completeness of an application to either eye, the drop should be immediately repeated. When testing infants and small children, use of a 2.5% solution of cocaine is recommended. The diameters of both pupils are measured before and 1 h after instillation of the drops, using the same levels of illumination for both measures. It is usually sufficient to measure the pupils' diameters with a pocket card that has semicircles of various diameters arrayed along one margin. If greater precision is desired, the measurements should be done with photography.

J Pearl

If 1 h after cocaine instillation there remains a difference between the pupillary sizes of 1 mm or more, this should be accepted as reasonable proof of Horner's syndrome (■ Fig. 5.3). If the anisocoria is less than 0.3 mm, it is most likely physiologic. However, one should take into account that 5% cocaine produces an average dilation of 2.1 mm in normal pupils and 0.5 mm in pupils affected by Horner's syndrome. Only 3% of Horner's-affected pupils respond with a dilation of more than 1 mm, so when cocaine produces a dilation of 1.5 mm or more, Horner's syndrome can be effectively ruled out.

Thus, cocaine testing clearly differentiates physiologic an-isocoria from Horner's syndrome. ■ Table 5.1 lists the limiting values. In cases of doubtful results, the test should be repeated. In the United States, where random testing by employers is common, subjects tested with cocaine should be given certificates indicating that they have been exposed to cocaine as a medical testing agent. The effect of topical administration of a 5% solution of cocaine to the eye can be detected in urine samples for several days.

Fig. 5.3. Horner's syndrome (right side) before and after cocaine test

Table 5.1. Cocaine testing for Horner's syndrome

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