Diplopia is the visual symptom of “double vision,” in which a single object appears as two separate images. With the exception of central polyopia, which is exceedingly rare, diplopia due to neurologic disease is always binocular. Due to ocular misalignment from brainstem, cranial nerve, neuromuscular junction, or extraocular muscle disease, the two eyes are pointed at different targets and thus see two different images, which are perceived as double vision. These symptoms resolve when either eye is covered, as with only one eye open there is only one image to see. Very subtle ocular misalignment can cause two images to overlap so much that they are not perceived as discrete images but rather as a single blurry image that resolves when either eye is covered (binocular blur). In contrast, diplopia due to ophthalmic disease persists when the unaffected eye is covered and represents an intrinsic ocular process that is causing two images to be projected onto the same retina.

Ocular motor function can be evaluated by assessing ocular motility and ocular alignment. Ocular motility assesses eye movement in different directions of gaze. If movement is clearly limited in one or more directions, the lesion can often be localized based on the pattern of extraocular muscles that are affected. However, a patient with binocular diplopia may appear to have full extraocular motility, either because the degree of extraocular muscle weakness is very subtle or because the disorder is one of gaze-holding, whereby the eyes are misaligned but the extraocular muscles themselves function normally. In this case, testing ocular alignment is helpful, most commonly with the alternating eye cover test. The patient is asked to fixate on a single target as the examiner alternates covering either eye. If the eyes are normally aligned, each remains steadily fixated on the target, and there are no refixation eye movements. If the eyes are misaligned, refixation movements will be observed during alternate eye covering.

If ocular misalignment worsens in one direction of gaze and improves in the other, it is referred to as incomitant . This suggests subtle specific extraocular muscle weakness. In contrast, if ocular misalignment is comitant , that is, equal in different directions of gaze, this argues against weakness of any particular extraocular muscle and suggests decompensation of a congenital strabismus or an acquired gaze-holding disorder.

The primary function of the superior oblique muscle, innervated by the fourth cranial nerve, is incyclorotation of the eye (rotation of the globe inward such that the superior aspect becomes displaced nasally and the inferior aspect rotates temporally), and its secondary function is depression. Because it is a relatively weak depressor, fourth nerve palsies are generally characterized by full ocular motility, and alignment testing is important for diagnosis. Vertical misalignment in a fourth nerve palsy (where the affected eye is the higher eye) increases in contralateral gaze and with ipsilateral head tilt. Many patients with fourth nerve palsy will have a visible contralateral head tilt as a means to correct for the ocular misalignment.

Third nerve palsies may be complete or partial, affecting some muscles more than others. A vertical misalignment that changes in upgaze and downgaze (one eye is lower than the other in upgaze but higher than the other in downgaze), even with full ocular motility, can indicate a third nerve palsy. Pupillary involvement may be present or absent and is more likely to occur with compressive lesions due to the somatotopic organization of the oculomotor nerve. Not all third nerve palsies need be “down and out.”

A skew deviation refers to a vertical misalignment due to an intrinsic brainstem lesion in the pathway responsible for maintaining tonic vertical eye position in response to head tilt. The localization of a skew deviation follows the “high-high, low-low” rule: if one eye is higher than the other, the lesion may be higher (midbrain) on the side of the high eye, or lower (pontomedullary junction) on the side of the low eye. Skew deviations are distinguished from fourth nerve palsies by their comitance (since no one cranial nerve nucleus is affected, the misalignment is generally equal in different directions of gaze).

Decompensated exotropia and esotropias are horizontal misalignments that present early in life. Their precise cause is unknown, but they are thought to represent abnormal development of binocularity and gaze-holding in the brain.

Myasthenia gravis and thyroid eye disease can present with isolated motility defects that can mimic any nuclear or internuclear eye movement abnormality. They should be suspected if there is a history of variable symptoms or if there are associated external and eyelid findings on examination (ptosis or orbicularis weakness for myasthenia gravis; eyelid retraction, proptosis, and periorbital edema for thyroid eye disease).