Ocular misalignment can present as double vision or even blurred vision. It is important to ascertain if the diplopia or blurred vision resolves when one eye is covered, thus, confirming the binocularity of the complaint. Binocular diplopia is explained by ocular misalignment, either related to supranuclear, internuclear, infranuclear, or restrictive causes. On the contrary, monocular diplopia is related to optical aberrations, refractive errors, or media opacities. 
Once binocular diplopia has been confirmed, it is important to determine whether it is comitant, with the same measurements in every direction of gaze, versus incomitant, where measurements vary with gaze direction. The former usually points towards a congenital cause of strabismus or a decompensated phoria. An incomitant deviation raises suspicion for an acquired disorder. However, this is not the rule; some congenital deviations can also be incomitant.
Supranuclear pathways comprise those that are used for volitional eye movements and the vestibular input that tweaks the eye position relative to the head position. Horizontal eye movements are regulated by a specific area called the paramedian pontine reticular formation (PPRF). When a lesion involves this region, the horizontal eye movements are restricted symmetrically. As a result of the symmetry, patients do not usually complain of diplopia. However, there are some supranuclear lesions that asymmetrically affect the area of interest. Skew deviation is one of the best examples. This is a vertical misalignment that can result from posterior fossa (either in the brainstem or cerebellum) or inner ear lesions. It can be either comitant or incomitant and may even present similarly to a fourth nerve palsy. However, the Parks-Bielschowsky three-step test (described later) is useful in differentiating the two conditions.
The typical internuclear cause of diplopia is the internuclear ophthalmoplegia (INO). Demyelination is the most frequent etiology in younger patients, whereas microvascular ischemic stroke is more common in the older population. INO results from the disruption of the medial longitudinal fasciculus (MLF) which connects the ipsilateral sixth nerve nucleus in the pons to the contralateral third nerve nucleus in the midbrain. It classically presents with reduced adducting saccadic velocity in the eye ipsilateral to the lesion as well as an abducting nystagmus in the contralateral eye.
Infranuclear causes comprise the isolated ocular motor nerve palsies. The lesions can be present from anywhere the nerves exit the brainstem.
Third nerve palsies usually present with partial or complete upper lid ptosis associated with partial or complete limitation of adduction, supraduction, and infraduction. Patients present with the eye deviated downward and outward, depending on the extent of the involvement. It is primordial to evaluate if the pupil is involved; a dilated, and poorly reactive pupil raises concern for a compressive lesion such as an aneurysm in the area where the posterior communicating artery and internal carotid join. Less commonly, in up to 20% of cases, a microvascular ischemic third nerve palsy can also affect the pupil. The anatomic reason for the pupillary involvement resides in the fact that the pupillomotor fibers travel at the superficial aspect of the nerve and are, thus, more prone to aneurysmal or tumor compression. However, it is recommended that in all cases of non-traumatic acquired third nerve palsies, urgent imaging with either magnetic resonance angiography (MRA) or computed tomography angiography (CTA) be performed to rule out a posterior communicating aneurysm.
Fourth nerve palsies can be divided as being congenital or acquired. Congenital fourth nerve palsies usually do not present with diplopia until much later in life. Patients typically have a chronic head tilt and facial asymmetry, as well as large vertical fusional amplitudes (more than three prism diopters). It is helpful to ask the patient to bring old photographs to document the chronic head tilt.
The most common cause of an acquired fourth nerve palsy is trauma. Patients are fairly symptomatic and complain of diplopia which is worse on downgaze when reading. The Parks-Bielschowsky three-step test is helpful in testing for fourth nerve palsies. It is characterized by a hypertropia in the affected eye that increases on opposite gaze and ipsilateral head tilt; for example, a left hypertropia would worse on right gaze and left head tilt.
Sixth nerve palsies are the most frequent of all ocular motor nerve palsies. Patients complain of horizontal diplopia that worsens on ipsilateral abduction, and the examination reveals an esodeviation in a primary gaze that increases with abduction in the affected eye.
Typically, the most common reason for an isolated unilateral ocular motor nerve palsy in patients older than 50 years old is related to microvascular ischemia. The latter tends to resolve within three months of presentation. All ocular motor nerve palsies that do not resolve within three months should be imaged. It is also important to remember to always rule out giant cell arteritis in patients older than 50 years old.
When multiple cranial nerves are affected (most specifically cranial nerves III, IV, V, VI) as well as the sympathetic nerves, producing an ipsilateral Horner’s syndrome, it is primordial to investigate for lesions in the cavernous sinus or the superior orbital fissure.
In all presenting cases of diplopia that do not fit with a specific pattern of an ocular motor nerve palsy of myasthenia gravis should always be in the differential diagnosis. This neuromuscular junction autoimmune disorder is characterized by variable ptosis and diplopia. The patient can present with pupillary-sparing ophthalmoplegia which can mimic any ocular motor cranial nerve palsy.
Thyroid eye disease should be sought in cases of presenting diplopia with proptosis, eyelid retraction, and lid lag. On neuroimaging, this type of restrictive strabismus often will show enlargement of the involved muscles with sparing of tendons.
The measurement of ocular misalignment is achieved with prisms, first using the cover-uncover testing method to determine if a tropia is present, and then using the alternate cover testing to measure the total amount of deviation; however, this doesn’t differentiate between a phoria and tropia.
Treatment depends on the underlying conditions. Usually, the treatment will be symptomatic and aimed at reducing the bothersome diplopia the patient experiences. In most cases, this is achieved with prismatic correction in glasses. In cases where the deviation is too large to be corrected with prisms and has been stable for a period of at least six months, strabismus surgery can be considered. Finally, conditions such as giant cell arteritis, myasthenia gravis, and thyroid eye disease have specific treatments, including corticosteroids in all cases, anticholinesterase medications and immunosuppressive agents in myasthenia gravis and orbital decompression, strabismus surgery, and lid surgery (in this specific order) for thyroid eye disease. 
Patients with diplopia may initially present to the emergency department physician, primary care provider and nurse practitioner. However, because there are many causes of diplopia and the workup is beyond the scope of the primary provider, these patients should be referred to an ophthalmologist for definitive workup. The prognosis depends on the cause.
|||Nakamizo A,Matsuo S,Amano T, Abducens nerve schwannoma: a case report and literature review. World neurosurgery. 2019 Feb 1; [PubMed PMID: 30716483]|
|||Raza HK,Chen H,Chansysouphanthong T,Cui G, The aetiologies of the unilateral oculomotor nerve palsy: a review of the literature. Somatosensory [PubMed PMID: 30592440]|
|||Seres L,Pethő G,Pető Z,Pető T, [Transient diplopia and ophthalmoplegia following dental anaesthesia. Review of the literature and case report]. Orvosi hetilap. 2018 Dec; [PubMed PMID: 30582357]|
|||Mori H, [Diplopia/Double Vision]. Brain and nerve = Shinkei kenkyu no shinpo. 2018 Dec; [PubMed PMID: 30523215]|
|||Peck T,Goldberg D, Double vision in adults. Journal of binocular vision and ocular motility. 2018 Jul-Sep; [PubMed PMID: 30196786]|
|||Disorders of Vergence Eye Movements., Brune AJ 3rd,Eggenberger ER,, Current treatment options in neurology, 2018 Aug 23 [PubMed PMID: 30136159]|
|||Nonsurgical treatment of diplopia., Bartiss MJ,, Current opinion in ophthalmology, 2018 Sep [PubMed PMID: 30096086]|