Marcus Gunn Pupil

Etiology

Lesions of the optic nerve are among the most common causes of an MGP. Conditions such as optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and glaucoma can damage retinal ganglion cell axons and impair afferent signaling.[1] Retinal and posterior segment disorders may also lead to an MGP through loss of photoreceptors or viable retinal tissue. These conditions include retinal detachment,[3][7] central retinal vein occlusion,[8] central serous chorioretinopathy (may not be clinically appreciable),[9] severe macular disease,[10] retinitis pigmentosa,[11] and endophthalmitis. In such cases, the magnitude of the defect often correlates with the extent and asymmetry of retinal damage.

Certain conditions may produce an apparent or induced MGP. Dense cataracts can create a contralateral RAPD due to increased intraocular light scattering and altered retinal illumination.[12] For the same reason, anisocoria greater than 2 mm can cause an MGP of the eye with the smaller pupil.[13] A temporary, contralateral MGP may occur after patching one eye, due to dark adaptation and increased retinal sensitivity of the patched eye.[14] Other factors, such as amblyopia, may occasionally produce subtle or artifactual pupillary asymmetry.[13][15]

Lesions involving the optic chiasm, optic tract,[16][17] or pretectal region may also produce an MGP.[18] Lesions of the optic chiasm, while less common than those of the optic nerve, may damage more fibers from one eye compared to the other, resulting in an MGP.[19] Lesions of the optic tract can cause a contralateral MGP due to more nasal fibers crossing at the chiasm than temporal fibers that stay on the ipsilateral side.[20] Unilateral lesions of the olivary pretectal area or the brachium of the superior colliculus can cause a tectal MGP, which is contralateral in nature and can present without vision loss due to the pupillary fibers branching off before reaching the visually processing areas.[6] An MGP should not be confused with the Marcus Gunn phenomenon (jaw-winking syndrome), a separate condition in which eyelid movement occurs during chewing.[21]

Epidemiology

An MGP does not exhibit a specific age or sex predilection. Findings from a study using a binocular pupillometer showed that 42% of the normal population had an MGP between 0.08 and 0.22 log units, and 6% had an MGP between 0.23 and 0.39 log units.[22] The presence of an MGP was attributed either to measurement inaccuracy or to actual synaptic asymmetries in the visual pathway. Findings from one of the most recent population-based studies evaluating MGP in a Syrian cohort showed that clinically significant MGP was identified in 7.9% of individuals, with a higher prevalence observed among older individuals.[23] Furthermore, an MGP is noted in more than 90% of cases of acute unilateral cases of optic neuritis, up to 90% of cases of central retinal artery occlusion, 91% cases of ischemic central retinal vein occlusion (CRVO), more than 50% cases of retinal detachment involving the macula, and 23% cases of primary open-angle glaucoma.[3][8][24][25][26]

Pathophysiology

When a bright light shines on one eye, the pupil constricts. This pupillary constriction is known as a direct light reflex. Simultaneously, the pupil of the other eye also constricts. This response in the contralateral eye is known as a consensual light reflex. The light reflex is mediated by retinal photoreceptors and subserved by 4 neurons.[27]

• The sensory afferent neurons connect each retina with both pretectal nuclei located in the midbrain at the level of the superior colliculus. Impulses from the nasal half of the retina decussate in the optic chiasm and pass via the contralateral optic tract to reach the contralateral pretectal nucleus. Impulses from the temporal half of the retina travel via the ipsilateral optic tract to reach the ipsilateral pretectal nucleus. Estimates suggest that the nasal fibers decussate within the chiasm in a ratio of crossed (nasal) to uncrossed (temporal) fibers of 53:47.[28] According to a new model, temporal retinal fibers may partially cross at the optic chiasm, in addition to the crossing of nasal fibers, leading to greater input from one eye into the contralateral optic tract.[17]

• The internuncial neurons connect each pretectal nucleus to both Edinger-Westphal nuclei that activate both the ciliary and pupillary sphincter muscles. Thus, a uniocular light stimulus evokes bilateral crystalline lens accommodation and pupillary constriction. This consensual light reflex results in a similar degree of pupillary constriction because pupillomotor output to both eyes is the same.[29]

• The preganglionic motor neuron connects the Edinger-Westphal nucleus to the ciliary ganglion. These fibers pass through the inferior division of the oculomotor nerve.

• The postganglionic motor neurons innervate the sphincter pupillae via short ciliary nerves.

An MGP is observed in lesions of the afferent arm of the light pathway. When the light is shifted from the normal eye to the abnormal eye, the total pupillomotor input is reduced, and the amount of pupillary constriction is less when compared to stimulation of the normal eye.[30] This difference in pupillomotor input results in an MGP.

Marcus Gunn Pupil in Lesions of the Optic Nerve

Ischemic optic neuropathies, such as arteritic and nonarteritic ischemic optic neuropathy, cause an MGP via ischemia and infarction of the optic nerve, with secondary optic nerve edema. Other diseases causing such asymmetric or unilateral damage to the optic nerve resulting in an MGP include glaucoma, anterior and retrobulbar optic neuritis, and traumatic optic neuropathy.

Marcus Gunn Pupil in Lesions of the Optic Tract

The axons of the retinal ganglion cells from the nasal retina decussate in the optic chiasm, joining the temporal fibers of the other side. In addition, a partial crossing of temporal fibers may occur in the chiasm.[17] Thus, an asymmetry of pupillomotor input into the optic tracts occurs, with greater input from one eye to the contralateral tract. Consequently, individuals with unilateral optic tract lesions may show an MGP in the eye contralateral to the lesion, which generally has a temporal field defect.[16][17]

Marcus Gunn Pupil in Lesions of the Pretectum

The asymmetry of pupillomotor input extends from the optic tract to the pretectal nucleus. Consequently, lesions of the pretectum produce an MGP in the contralateral eye. The MGP in such situations is without the associated loss of visual acuity, color vision, or visual field, because just before fibers reach the lateral geniculate body (light pathway), a few fibers (pupillary reflex) branch off to the pretectum. Therefore, for lesions at the brachium of the superior colliculus adjacent to the pretectal nucleus, vision is not affected.[18]

Marcus Gunn Pupil in Glaucoma and Visual Field Defects

In conditions such as glaucoma, an MGP occurs secondary to damage to retinal ganglion cells and loss of the retinal nerve fiber layer.[31] At least 26% of retinal ganglion cells should be damaged to elicit an MGP.[32] An MGP is observed only when glaucomatous damage is asymmetrically severe. An MGP may be noted even before the appearance of diagnostic glaucomatous visual field defects.[33] Findings from studies showed that the central 30° of the visual field provides the most pupillomotor input, and asymmetrical visual field loss outside of 30° is much less likely to result in an MGP.[34]

Marcus Gunn Pupil in Retinal Disorders

An MGP occurs secondary to the loss of functional photoreceptors in the retina.[10] The central retina provides the most pupillomotor input, resulting in a greater pupillary response than the same stimulus applied to the peripheral retina.[35] Consequently, detachment of each peripheral quadrant of the retina causes an estimated 0.35 log unit light sensitivity loss, while detachment of the macula causes a 0.68 log unit loss.[7] Ischemic CRVO typically produces over a 0.9 log unit loss, whereas nonischemic CRVO produces less than a 0.6 log unit loss.[8] Most macular diseases do not cause an MGP unless they are very severe.[36] In macular disease, visual acuity declines more relative to the degree of MGP, whereas in optic neuropathy, vision loss may correlate more closely with MGP level.[9] Localized macular dystrophies and degenerations, as well as diffuse retinal dystrophies such as retinitis pigmentosa, usually do not show an MGP response unless the disease is asymmetric. Even in that case, the MGP may be subclinical. However, variants such as unilateral retinitis pigmentosa can show an MGP usually of under 0.3 log units.[11] Central serous chorioretinopathy may cause a mild MGP (usually ≤0.4 log units, but sometimes up to 0.9 log units), which improves with the resolution of subretinal fluid.[9]

Induced Marcus Gunn Pupil

Marcus Gunn pupil in cataract: The occurrence of an MGP in cataracts is controversial because an MGP usually indicates underlying damage to the afferent visual pathway (optic nerve or retina) rather than the cataract itself. Since Galen's time, an MGP has been noted to indicate poor visual prognosis after a cataract surgical procedure.[4] When a dense cataract causes an MGP in the contralateral eye, the MGP occurs by increasing the pupillomotor effectiveness of the stimulus light, likely because of increased intraocular light scattering by the cataract.[12] Peripheral photoreceptors may be stimulated by diffusely scattered light, and the light may bounce back again on the retina due to reflection by the posterior surface of the cataract.[12] Additionally, a dense cataract may induce dark adaptation of the affected eye.[12] A mature cataract can induce a mean of 0.44 log units (maximum 0.6 log units) defect in the contralateral eye, which disappears after cataract extraction.[12]

Marcus Gunn pupil in eye patching and dark adaptation: Ocular occlusion due to patching of the eye or eye disease, such as an eyelid mass or ptosis, increases retinal sensitivity via dark adaptation and can cause a false MGP of up to 1.50 log units in the unoccluded eye. This induced MGP disappears within 30 minutes of examination in an illuminated room after the eye occlusion has been removed.[14]

Marcus Gunn pupil in anisocoria: In anisocoria, the retina in one eye is shaded by the iris more than the other. This difference in retinal illumination can produce an RAPD in the eye with the smaller pupil. For every 1 mm difference in pupil size, a 0.10 log unit defect in RAPD is noted. Therefore, a 3 mm difference between the pupils can produce a clinically detectable RAPD. This artifactual pupillary response can be alleviated by placing neutral-density filters over the larger pupil at a rate of 0.10 log unit per millimeter of anisocoria.[13][37]

Miscellaneous

Marcus Gunn pupil in amblyopia: According to classic teaching, a structural abnormality of the retina or optic nerve is not present in amblyopia; consequently, an MGP should not be present. However, a study of individuals with amblyopic eyes found that an easily visible MGP (greater than 0.3 log units) was observed in 29 of 55 individuals (52.7%), and 45 of 55 individuals (81.8%) had a detectable MGP. Although most cases had an MGP of up to 0.6 log units, some showed a lower MGP of less than 0.3 log units, detected using a modified standard RAPD test.[15] The cause of MGP in amblyopic eyes is unknown,[38] but it is associated with impaired development of X ganglion cells in the fovea of the amblyopic eye. Studies have not revealed a correlation between amblyopia severity and MGP grade.[38]

History and Physical

Patients with an MGP can present with normal visual function or may have symptoms of an underlying disorder. For example, an MGP can persist after optic neuritis resolves and vision returns to normal.[18][39][40] Although this is often a point of confusion for medical trainees and staff, an MGP does not cause anisocoria.[41]

Ocular Examination

• Visual acuity: May range from 20/20 to light perception
• Ocular alignment: Patients with long-standing vision loss may manifest sensory strabismus
• Assessment of pupils: 
  • A weaker initial constriction with greater redilatation
  • An initial stall with greater redilatation
  • An initial and immediate dilatation, known as pupillary escape

• Pupillary escape: A specific and evident sign of MGP and is not to be confused with hippus, which is a natural rhythmic oscillation in the pupil diameter [42]
• Anterior segment examination: The presence of iris neovascularization should raise suspicion of ischemic CRVO
• Fundus evaluation: Helps to identify underlying causes such as optic neuropathy (eg, optic neuritis and ischemic optic neuropathy), retinal detachment, retinal vascular occlusion, glaucoma, and other pathologies

Supportive Tests

Supportive tests include optical coherence tomography of the retina and optic nerve, fluorescein angiography, fundus autofluorescence, visual field testing, color vision, contrast sensitivity, visual evoked potential, and MRI in cases of optic neuritis. Brightness acuity testing can be performed to rule out crystalline lens (cataract) or corneal (eg, Fuchs dystrophy) pathology. Please see StatPearls' companion resource, "Tests for Potential Vision," for further information.

Evaluation

An MGP typically indicates disease in the prechiasmal visual pathway.[4] The ability to detect and quantify an MGP is an essential part of the neuro-ophthalmic examination.

Tests to Identify and Quantify an MGP

• Gunn test
• Kestenbaum-Gunn test and modified Gunn test
• Swinging flashlight test
• Pupillography

The use of neutral density filters and cross-polarized filters aids in quantifying an MGP when used in conjunction with the swinging flashlight test or the Modified Gunn test.[37][43] RAPD severity correlates with retinal nerve fiber layer thinning and ganglion cell layer damage.[44]

Gunn test

The original description of a clinical test for an RAPD was reported by the Scottish physician Robert Marcus Gunn in 1902. In contrast, some literature suggests that the German ophthalmologist Julius Hirschberg had already noted the phenomenon of pupillary light reflex attenuation in unilateral optic nerve disease 20 years prior.[45] The original Gunn test involved covering and uncovering the eye in bright light and observing the pupillary response. A positive response was recorded when the pupil of the affected eye failed to constrict promptly compared with the unaffected eye.[46]

Modified Gunn test, Kestenbaum-Gunn test, and swinging flashlight test

In a 1946 publication, the Austrian physician Alfred Kestenbaum named RAPD testing and the pupillary response for Marcus Gunn. Occasionally, the test is named after both of them (Kestenbaum-Gunn test). In 1959, the American ophthalmologist Paul Levatin introduced and popularized the swinging flashlight test. His method was a modification of the original test in which, instead of occluding the eye, a bright light was alternately shone into each eye. The swinging flashlight test also standardized the illumination duration for each eye, ensuring accurate results. A study found that the original Gunn test correctly identified an MGP in 57% of cases, compared to 93% with the swinging flashlight test.[36][47][48][47]

Swinging flashlight test procedure:

• Perform the test in a semi-dark room and ask the patient to fixate on a distant letter or pattern (looking at a near object causes accommodative miosis).
• Shine a focused light source, such as a penlight or an indirect ophthalmoscope, into one eye from below the patient's eye at a distance of 5 to 10 cm.
• After a 3-second pause, quickly shift the light to the other eye.[49] 
• Move the whole light from side to side, keeping the distance and angle equal. Holding the light in front of the nose and sequentially illuminating the 2 pupils by shifting the angle away from the central axis can stimulate the near response.
• Alternate the light between the 2 eyes, pausing 3 seconds on each eye.
• Look for a change in pupil size as the light is alternated.
• An MGP dilates when illuminated. The contralateral (unilluminated) pupil should dilate at the same time.

Clinical grading of RAPD based on the swinging flashlight test: 

The grades are determined by averaging pupillary responses over at least 6 light swings:

• Grade 1: A weak initial constriction and greater redilatation
• Grade 2: An initial stall and greater redilatation
• Grade 3: An immediate dilatation
• Grade 4: An immediate pupillary dilatation (followed by secondary constriction) following prolonged illumination of a good eye for 6 seconds (bleaching of the normal eye)
• Grade 5: An immediate pupillary dilatation with no secondary constriction following prolonged illumination of a good eye for 6 seconds [49] 

Grades 4 and 5 are elicited after bleaching the photoreceptors of the good eye to reduce its pupil power.

Reverse method RAPD testing:

When an efferent defect results in an unresponsive or fixed pupil, detecting an MGP remains possible by performing a modification of the swinging flashlight test.[36] When a pupil cannot react because of posterior synechiae, pharmacological immobilization, trauma, or other physical or neurological damage, clinicians should focus on the reactive pupil. The modification is as follows:

• Illuminate the reactive pupil from the side with a dim light that is bright enough to observe pupillary responses. Do not shine this light directly into the pupil.
• Complete the swinging flashlight test.
• If an MGP is present in the eye with an unresponsive pupil, when light is thrown onto the normal eye, its pupil constricts. When the light is moved to the abnormal eye, the pupil in the normal eye dilates or constricts less. Returning the light to the normal eye causes its pupil to constrict again.
• The unresponsive pupil may be larger or smaller than the responsive pupil, which can alter the relative illumination of the retina and affect the test result.

Quantification of Marcus Gunn Pupil Using Neutral-Density Filters

Quantification is performed by placing a neutral-density filter over the better eye and then performing a swinging flashlight test. The stimulus in the better eye is reduced by applying a neutral density filter (typically 0.3, 0.6, 0.9, or 1.2 log units), and the swinging flashlight test is performed with increasing filter densities. The endpoint of the test is achieved when the pupillary responses are equal. The filter density required to reach this point is recorded in log units to quantify the defect size. The smallest detectable defect is 0.3 log units. Clinicians should avoid light spill at the edge of the filters as the light is swung from one eye to the other. Because the neutral density filter blocks light, visualizing the pupil beyond a 1.2 log unit neutral density filter is difficult, necessitating the examiner to look around the filter to observe the pupillary reflex. During the first attempt, overshooting the endpoint and inducing a pseudo-RAPD in the better or filtered eye is preferable, after which the filter density can be reduced.[37][49]

Using Neutral-Density Filters to Test for a Subtle Marcus Gunn Pupil

To unmask a subtle MGP, a neutral density filter of 0.3 log units is placed in front of the eye with suspected optic neuropathy, and the swinging flashlight test is then performed. Placing the neutral density filter in front of the weak eye further decreases the pupillomotor input of that eye and heightens the intereye pupillomotor input difference, thereby unmasking the RAPD.[15][36][50]

The Kestenbaum Number

In individuals with unilateral optic nerve disease, when one eye is covered and the other is exposed to bright light, the pupil of the affected eye dilates to a larger diameter. This difference (in millimeters) in the size of the 2 pupils is a measure of the difference in pupillomotor input between the 2 eyes and roughly corresponds to the RAPD measured in log units of neutral density filter.[30]

Limitations

The swinging flashlight test is subject to various sources of inconsistency, including interindividual variability, the clinician's experience, ambient lighting conditions, patient cooperation, and the lack of precise quantification criteria. Measuring the Kestenbaum number or quantifying an MGP is difficult in children because of hippus, in older adults because of age-related miosis, and in any individual with reduced iris mobility.[30]

Pupillography

Modern pupillography uses a computerized device to simulate the swinging flashlight test, enabling more accurate detection and quantification of MGPs.[51] These are binocular pupillometers that provide information on pupil diameter, pupil diameter-time curves, and symmetry of pupillary responses. The data studied in pupillography include average pupillary constriction amplitude, constriction velocity, and constriction onset latency. Constriction amplitude is the best parameter for detecting MGPs and differentiating patients from normal subjects.[52] Recent advances, such as camera-based automated pupillometry and virtual reality–based eye-tracking systems, enable objective detection of RAPD and may facilitate its use in teleophthalmology.[53] Newer techniques, such as ultrasonography pupillometry, may detect subtle optic nerve dysfunction even when the clinical swinging flashlight test does not reveal an RAPD.[54]

Treatment / Management

MGP has no specific treatment. Treatment is directed toward the underlying disorder affecting the afferent visual pathway. Because an MGP most commonly indicates pathology of the optic nerve, retina, or visual pathways, prompt evaluation and treatment of the causative condition are essential to prevent vision loss and other complications. Management strategies depend on the underlying etiology. The most common causes of an MGP include:

• Optic neuritis: Diagnosis may include magnetic resonance imaging, optical coherence tomography, visual evoked potential testing, and various laboratory tests. Treatment may include corticosteroids.[55]
• Ischemic optic neuropathies: Diagnosis may include clinical observation, laboratory testing (including erythrocyte sedimentation rate, C-reactive protein, and platelet count), fluorescein angiography, and a temporal artery biopsy, and is managed by controlling risk factors and initiating immediate corticosteroid treatment when giant cell arteritis is suspected.[56][57]
• Asymmetric glaucoma: Glaucoma is evaluated using tests such as measurement of intraocular pressure, optical coherence tomography, visual field testing, pachymetry, and gonioscopy. Treatment requires reducing intraocular pressure with topical medications, laser therapy, or surgical procedures.[58]
• Optic nerve compression or trauma: Diagnosis is facilitated by computed tomography and magnetic resonance imaging, as well as visual function tests such as color vision and visual field testing. Management of orbital tumors, thyroid eye disease, or trauma to the optic nerve ranges from surgical decompression (acute trauma or thyroid eye disease), high-dose corticosteroids (inflammation or thyroid eye disease), or observation in some cases.[59][60]
• Extensive retinal damage: Severe, unilateral retinal disorders, such as retinal detachment, central retinal vein occlusion, or large retinal infections, require prompt ophthalmologic evaluation with B-scan ultrasonography, fundus photography, angiography, and optical coherence tomography. Treatment options include surgical repair and systemic and intravitreal pharmacologic therapy.[61][62]
(B3)

Careful clinical assessment should precede pharmacologic pupil dilation, especially when a patient presents with vision loss. Early diagnosis, appropriate referral to ophthalmology or neurology, and coordinated follow-up are essential to preserve visual function and improve clinical outcomes.

Differential Diagnosis

Hippus

Continuous oscillations of the pupil are often observed under constant retinal illumination.[63]

Alternating Contraction Anisocoria

Alternating contraction anisocoria is an uncommon syndrome of the anterior midbrain in which light stimulation of one pupil causes it to constrict more than the other, causing the contralateral pupil to appear larger. As the light stimulus is moved to the other pupil, this pupil now constricts more, leaving the original pupil as the larger one. This condition appears to the clinician as alternating anisocoria and RAPD. The cause is hypothesized to be a lesion at the posterior commissure and one or both brachia of the superior colliculus because of damage to a combination of both first- and second-order neurons. Alternating contraction anisocoria can present in otherwise healthy individuals or result from viral encephalomyelitis, syphilis, or traumatic brain injury.[29]

Prognosis

The prognosis of MGP varies according to the cause:

• In optic neuropathy, the MGP magnitude often correlates with the degree of visual acuity loss, whereas in maculopathy, vision impairment exceeds that reflected by RAPD.[9] 
• In glaucoma, an MGP is objective evidence of visual field loss,[25] and can signify the earliest onset of optic nerve damage in patients with ocular hypertension.[64] Combining MGP assessment with ocular coherence tomography angiography may help detect early asymmetric glaucoma by identifying both functional and microvascular changes.[44] 
• In retinal vein occlusion, an MGP of over 0.9 log units is associated with extensive capillary nonperfusion and poor visual acuity that is typically worse than 20/400 (3/60).[8] A significant increase in MGP degree in a patient with nonischemic CRVO is an early indicator of conversion to ischemic CRVO.
• In retinal detachment, an MGP typically occurs in retinal detachment involving the macula, and postoperative visual acuity is typically lower in detachments involving the macula.[65] 
• In cataract, if the patient has an MGP in the same eye, postoperative visual gain tends to be poor due to associated defects in the anterior visual pathway.[12] A poor visual prognosis should always be explained in this case.

Complications

Failure to detect this clinical sign results in complications related to the underlying etiology. Most of the pathology associated with an MGP represents advanced disease of the posterior segment (retina and optic nerve) and brain (optic chiasm, optic radiations, and pretectal area), which is more likely to sustain rapid, irreversible injury than disease of the anterior segment. In cases such as arteritic anterior optic neuropathy or a compressive malignant lesion, detecting an MGP can be both sight-saving and life-saving.