Optic Atrophy Workup

The type of neuroimaging study depends on the disease process.

• For tumors located in the orbit, ultrasonography can be performed in addition to CT scanning or MRI. For papilledema, B-scan ultrasonography may show optic sheath dilatation.

• To find out whether a lesion is cystic or solid (eg, cysticercoids), CT or MRI is recommended. For solid lesions, MRI (with contrast or fat suppression) is preferred in areas in close proximity to the bony wall.

• For fractures associated with trauma, a noncontrast CT scan is preferred.

• For multiple sclerosis, a gadolinium-enhanced MRI/fluid-attenuated inversion recovery (FLAIR) sequence is useful to detect hyperechoic areas.

Visual acuity testing

Visual acuity is measured using Snellen optotypes or a LogMAR chart. Visual acuity is reduced, occasionally to no light perception.

Stimulus parameters affecting visual acuity include contrast of the chart, refractive error, pupil size, stimulus eccentricity, duration of stimulus presentation, type of optotype used, illumination, and crowding phenomenon.

Color vision testing

Color vision is more decreased in patients with optic nerve disorders than in those with retinal disorders, especially among individuals with ischemic and compressive optic neuropathy. Prerequisites for color vision testing include proper lighting (both an adequate amount of light and the proper spectral distribution). Color vision is profoundly decreased compared to visual acuity in patients with ischemic and compressive optic neuropathy.

Color vision may be assessed with pseudoisochromatic tests (eg, Ishihara color blindness test, Hardy-Rand-Rittler polychromatic plates, Dvorine plates) or the Farnsworth-Munsell 100 Hues test or Farnsworth panel D-15 test.

Contrast sensitivity test

This test measures the ability to perceive slight changes in luminance between regions that are not separated by definite borders and is a sensitive test for optic nerve function.

Tests used to measure contrast sensitivity include the following:

• Pelli-Robson contrast sensitivity chart. Each letter subtends an angle of 3 degrees at a distance of 1 meter. Letters are organized in triplets with two triplets in each line. The contrast decreases from one triplet to the next. The log contrast sensitivity varies from 0.00-2.25.
• Cambridge low-contrast grating test
• Arden gratings

Factors that affect measurement include suboptimal refractive correction and duration of stimulus presentation.

Pupillary evaluation

Pupil size should be noted, as well as the magnitude and the latency of the direct and consensual responses to light and near stimulation. A relative afferent pupillary defect (RAPD) is a hallmark of unilateral afferent sensory abnormality or bilateral asymmetric visual loss. Occasionally, RAPD is the only objective sign of anterior visual pathway dysfunction. It is a sensitive optic nerve function test.

RAPD can be quantitatively graded by balancing the defect; successive neutral density filters are added in 0.3 logarithmic steps over the normal eye while performing the swinging flashlight test until the defect disappears. The most useful neutral density filters are from 80% (0.1 log unit) to 1% (2.0 log units).

Clinically, it is graded as follows:

• Immediate dilation of the pupil, instead of normal initial constriction (3-4+)
• No changes in initial pupillary size, followed by dilation of the pupils (1-2+)
• Initial constriction, but greater escape to a larger intermediate size than when the light is swung back to normal eye (trace)

Edge-light pupil cycle time

A thin beam of light is shown horizontally across the inferior aspect of the pupillary margin. The light induces pupillary constriction that moves the light out of the pupil. The pupil then redilates until the beam is once again at the edge of the pupillary margin, whereupon it constricts again, creating another cycle.

The time is calculated in milliseconds per cycle. Alternatively, the number of cycles in 1 minute is measured. The rate is normally 900 milliseconds per cycle.

Photostress recovery test

Principle-visual pigments bleach when exposed to an intense light source, resulting in a transient state of sensitivity loss and reduced central visual acuity.

To perform the test, the examiner should note the patient’s best-corrected visual acuity, shield one eye, and then ask the patient to look directly at a bright focal light that is held 2-3 cm from the eye for about 10 seconds. The time needed to return to within one line of best-corrected visual acuity level is measured; this time is the photostress recovery time.

Pulfrich phenomenon

In optic nerve damage, the transmission of impulses to the occipital cortex is delayed. In patients with unilateral or markedly asymmetric optic neuropathy, when an oscillating small target in a frontal plane is viewed binocularly, the target appears to move in an elliptic path rather than in a to-and-fro path.

Cranial nerve examination

All cranial nerves are examined to rule out associated nerve involvement to help determine the site of the lesion.

Extraocular movements

Restriction can be obtained in cases of compressive optic neuropathy due to either the mass effect or the involvement of the nerve supplying the muscle.

Ophthalmoscopic features

Optic disc

Optic disc changes can present with temporal pallor (as seen in toxic neuropathy and nutritional deficiency), focal pallor or bow-tie pallor (as seen in compression of the optic chiasma), and cupping (as seen in glaucomatous optic atrophy).

In the early stages of the atrophic process, the optic disc loses its reddish hue, and the substance of the disc slowly disappears, leaving a pale, shallow concave meniscus, the exposed lamina cribrosa. In the end stages of the atrophic process, the retinal vessels of the normal caliber still emerge centrally through the otherwise avascular disc.

Optic disc cupping also develops in patients with normal intraocular pressures and optic atrophy from various causes, including ischemia, compression, inflammation, hereditary disorders, and trauma.

Focal or diffuse obliteration of the neuroretinal rim with preservation of color of any remaining rim tissue is specific for glaucoma.

Peripapillary retinal nerve fiber layer

Early focal loss of axons is represented by the development of dark slits or wedges in the peripapillary retinal nerve fiber layer (RNFL). These slits or bands appear darker or redder than the adjacent healthy tissue. The slit defects are most easily identified in the superior and inferior arcuate regions, where the nerve fiber layer is particularly thick.

Retinal vessels

In most cases of optic atrophy, the retinal arteries are narrowed or attenuated. In cases of nonarteritic anterior ischemic optic neuropathy, the vessels may be focally narrowed or completely obliterated. Nonarteritic anterior ischemic optic neuropathy is shown in the images below.

Investigations

Visual field testing

Field testing methods include kinetic and static. In the kinetic method, the contours of the island are mapped at different levels, resulting in one isopter for each level tested. In the static method, the vertical contours of the island are mapped along a selected meridian.

As per the areas tested, the visual field is divided into the central visual field, which has a 30-degree radius, and anything beyond 30 degrees is called peripheral visual testing. The central visual field can be tested using an Amsler grid, confrontation techniques, a tangent screen, and a bowl perimeter. Peripheral visual testing includes automated perimetry and manual perimetry. Automated perimetry tests the central 60 degrees of the visual field, whereas manual perimetry tests the entire visual field.

In optic neuropathy, visual field changes can include enlargement of the blind spot and paracentral scotoma (eg, optic neuropathy), altitudinal defects (eg, anterior ischemic optic neuropathy, optic neuritis), and bitemporal defects (eg, compressive lesions, similar to optic chiasma tumors).

Optical coherence tomography

Optical coherence tomography (OCT) measurements of retinal nerve fiber layer (RNFL) provide an objective measurement of nerve atrophy, offering quantitative analysis of retinal thickness and retinal nerve fiber layer. ^[9]

Multiple sclerosis (MS)

OCT shows thinning of the RNFL and the ganglion cell layer, correlating with structural aspect and visual dysfunction. It is used as a marker in the follow-up of patients with MS. The decrease in peripapillary RNFL thickness (approximately 10-40 µm) is maximal at 3-6 months after the acute episode, and stabilization is observed at 7-12 months. ^[10]

NAION

Initially, OCT shows RNFL thickness owing to edema, but the RNFL thins by about 40% at 3-4 months compared a normal eye. Ganglion cell thickness analyses in the early stage reveals axonal damage when the RNFL is edematous. ^[11]

Compressive lesion

Axonal loss can be quantified by RNFL and ganglion cell analysis. Patients with normal RNFL analysis findings tend to experience improved vision and visual field compared with patients who have altered RNFL status.

Hereditary optic neuropathy

In late stages, OCT shows RNFL loss. In healthy carriers, OCT results show RNFL thickening in temporal quadrants. ^[12]

Electroretinography

Abnormal electroretinography (ERG) results that can be seen are as follows:

• Subnormal: Potential less than 0.08 microvolts; seen in toxic neuropathy
• Negative: When a large a-wave is seen; may be due to giant cell arteritis, central retinal artery occlusion, or central retinal vein occlusion
• Extinguished: Response seen in complete optic atrophy

Visually evoked response

In optic neuritis, the visually evoked response (VER) has an increased latency period and a decreased amplitude as compared to the normal eye.

Compressive optic lesions tend to reduce the amplitude of the VER, while producing a minimal shift in the latency.

Blood Tests and Other Tests

As optic atrophy is a sign of end-stage optic nerve damage and not a diagnosis in itself, further investigation is required if a cause is not established. The following additional tests may be used:

• MRI of the brain and orbits with contrast (in addition to space-occupying lesion [SOL], look for sinusitis, hyperpneumatized sinuses, fibrous dysplasia)
• Blood glucose level
• Blood pressure, cardiovascular examination
• Carotid Doppler ultrasonography
• Vitamin B-12 levels, heavy metal screen
• Venereal Disease Research Laboratory (VDRL)/Treponema pallidum hemagglutination (TPHA) tests
• Antinuclear antibody levels
• Sarcoid examination
• Homocysteine levels
• Antiphospholipid antibodies
• Enzyme-linked immunosorbent assay (ELISA) for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus (TORCH panel)
• OPA1 blood testing in patients with a family history suggestive of dominant optic atrophy, especially young individuals with progressive bilateral vision loss and cecocentral scotoma with temporal disc pallor
• Leber hereditary optic neuropathy testing, especially in male patients with a family history of vision loss in maternal uncles