Extracts from an article in Review of Optometry 2019.
A patient presenting with diplopia—whether horizontal, vertical or diagonal—is often a clinical challenge. Constant diplopia with acute onset will have different differentials than intermittent diplopia, for example. While the cause can be benign, some cases, such as those accompanied by new headache, ocular pain, unilateral pupil dilation, muscle weakness, ptosis, trauma or papilledema, raise red flags for immediate referral. Most etiologies will fall into one of five categories: (1) refractive, (2) binocular vision disorder, (3) orbital disease, (4) neuromuscular junction dysfunction, or (5) injury to the central nervous system/cranial nerves (CNs). A systematic approach to the differentials is key to identifying and treating benign causes—and promptly referring patients when it is vision or life threatening.
Horizontal diplopia, when the images are truly side-by-side, is suggestive of a medial or lateral rectus under action or restriction.
Differential diagnosis for horizontal diplopia at distance includes unilateral or bilateral CN VI palsy, internuclear ophthalmoplegia (INO), age-related decompensating esophoria or muscle restriction, most commonly from thyroid disease, a space occupying lesion or myasthenia gravis (MG).
Here some common underlying etiologies of binocular diplopia:
Refractive. Misalignment of the optical centers of prescription glasses or non-prescription reading glasses, poor fitting glasses and the edges of high prescription glasses may all cause diplopia or worsen an existing heterophoria. Aniseikonia from refractive error results in differences in image size and shape in the visual cortex, causing diplopia when wearing glasses. Contact lens use often resolves the image difference in most cases of aniseikonia.1
Binocular vision disorder. A patient with a history of childhood strabismus may develop diplopia later in life due to a decompensation of their misalignment.10 Decompensating phorias and vergence problems are the most common cause of diplopia at near only. Asthenopia occurs with extended near activities, resulting in diplopia and headaches. Convergence insufficiency results in diplopia after prolonged near work and may be associated with uncorrected refractive error, dry eye and Parkinson’s disease.1
Orbital disease. Thyroid eye disease (TED), idiopathic orbital inflammation and orbital tumors are the most common extraocular muscle and orbital diseases that cause diplopia.2,3 Orbital inflammation is usually unilateral and may affect the orbital fat, extraocular muscles, lacrimal gland, sclera or optic nerve. Onset may be sudden and painful, and the eye may appear proptotic. This has been associated with rheumatoid arthritis, sarcoidosis and, less frequently, giant cell arteritis (GCA). Testing includes rheumatoid factor, chest x-ray and ACE level for sarcoidosis and anti-nuclear antibody for systemic lupus erythematosus.
Cranial nerve palsies. CN III, IV and VI palsies share many of the same underlying etiologies such as microvascular CN palsies, intracranial aneuryms and neoplasms.10,20 Trauma can impair the function of any nerve, but CN IV in particular is more susceptible to trauma. Microvascular disease accounts for many CN palsies in patients older than 50, especially in those with known microvascular disease. Pain and rapidity of onset provide less definitive clues about cause, should a cerebrovascular accident be suspected. ... A CN VI palsy is the most common, followed by CN IV and CN III.7 In all cases of nerve palsies, evaluation must carefully determine if single or multiple nerves are involved, as imaging is most often warranted, particularly when multiple cranial nerves are involved.21
CN VI innervates only the lateral rectus muscle, and paralysis causes an estropia from an abduction deficit. It is the most common isolated ocular motor palsy and accounts for 50% of them.8 The patient reports horizontal diplopia that is worse at distance and worse when looking in the direction of the affected muscle. Microangiopathic disease causes up to 36% of isolated, acute CN VI palsies in patients older than age 50 with vascular risk, and diplopia spontaneously resolves within two to three months.2,8 Wernicke’s encephalopathy, MS and Duane’s retraction syndrome may be mistaken for a CN VI palsy and should be considered in the differentials.2,5,7 In all other patients with an acute CN VI palsy, assessment for causes such as GCA, tumors, intracranial hemorrhage and trauma warrant referral to the emergency room for evaluation and imaging studies.8,17 If increased intracranial pressure is the underlying cause of a CN VI palsy, a thorough evaluation should include optic nerve head assessment for the presence of associated papilledema.8,17
Patients with palsies with ischemic causes are usually older with risk factors such as diabetes, hypertension, hyperlipidemia and tobacco use. Pupil evaluation may help narrow the differential, as the pupillary fibers reside on the dorsomedial aspect of the oculomotor nerve and are affected in 90% of compressive pathologies, causing a fixed, dilated pupil. In contrast, microvascular ischemia causes an infarct in the center of the nerve, which spares the pupil in 70% of ischemic cases. Up to 30% of ischemic palsies will have an anisocoria of 1mm to 2mm. Ischemic palsies usually improve within three months, and never demonstrate aberrant regeneration. The pupil rule cannot be applied to rule out a compression lesion when the palsy in incomplete.
Researchers have debated the use of imaging in all CN palsies for some time, and most agree those with an acute isolated CN III palsy need urgent imaging to rule out a compressive aneurysm or suspected cavernous sinus thrombosis. Imaging of the brain and orbits is appropriate in suspected retro-bulbar mass, TED or orbital trauma. In patients older than 60, referral for urgent bloodwork is indicated to rule out GCA.
However, a literature review shows that, for CN VI palsies, no definitive answer for imaging exists, as both prospective and retrospective cohorts had valid arguments for their conclusions of imaging all patients with isolated CN VI palsies. Thus, clinicians should always consider imaging CN palsies, especially when presenting with other neurological signs and symptoms.
Diplopia can be a concerning condition for any clinician to address. The key to following the right course of action is determining the underlying etiology. Primary care optometrists often have patients complain of diplopia, and with the right tools and skills, every OD can properly treat, coordinate a proper referral and often reassure the patient with a benign presentation.
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