Contrast sensitivity testing
Whereas visual acuity testing uses targets that vary in size but have a single high level of contrast, contrast sensitivity testing uses targets with varying contrast levels. Two types of contrast sensitivity tests exist: (1) grating tests and (2) letter tests. Grating tests display rows of sine wave grating patches, each row reflecting a different spatial frequency. Grating tests, although arguably superior to letter tests, are difficult to administer and to reproduce reliably. The Pelli-Robson chart, which is commonly used for clinical letter testing, consists of letters of a fixed size that vary in contrast. The minimum level of contrast at which the letters can be detected is recorded.
Contrast sensitivity testing can detect and quantify vision loss in the presence of normal visual acuity. Such testing, however, is not specific for optic nerve dysfunction; media irregularities and macular lesions may also yield abnormal results. Interpretation of contrast sensitivity test data is more complex than interpretation of visual acuity data, particularly with regard to differentiating subtle abnormalities from normal presentation.
Contrast sensitivity testing is discussed further in BCSC Section 3, Clinical Optics, and Section 12, Retina and Vitreous.
Owsley C. Contrast sensitivity. Ophthalmol Clin North Am. 2003;16(2):171–177.
Photostress recovery testing
The photostress recovery test may help differentiate vision loss caused by a macular lesion or ocular ischemia from that caused by an optic neuropathy. CDVA is measured (a visual acuity of 20/80 or better is required). Tested monocularly, the patient gazes directly into a strong light held 2–3 cm from the eye for 10 seconds. As soon as possible after the light is removed, the patient attempts to read the next larger Snellen visual acuity line above the line representing the patient’s CDVA (eg, a patient with a CDVA of 20/25 attempts to read the 20/30 line). Normal photostress recovery time is less than 30 seconds, but patients with maculopathy or severe carotid artery stenosis have prolonged recovery times, frequently 90–180 seconds or more. Patients with optic neuropathy maintain normal photostress recovery times.
Glaser JS, Savino PJ, Sumers KD, McDonald SA, Knighton RW. The photostress recovery test in the clinical assessment of visual function. Am J Ophthalmol. 1977;83(2):255–260.
Potential acuity meter testing
Potential acuity meter (PAM) testing can help determine whether media irregularities or opacities are the cause of decreased vision. Optotypes are projected onto the retina through a dilated pupil, providing an estimate of best potential visual acuity. If the visual acuity does not improve to 20/20 with PAM, the ophthalmologist should search for a cause other than media opacities, such as optic neuropathy or maculopathy.
Reid O, Maberley DA, Hollands H. Comparison of the potential acuity meter and the visometer in cataract patients. Eye. 2007;21(2):195–199.
Fluorescein angiography may have a role in the investigation of some optic neuropathies. Angiographic leakage can differentiate true edema from pseudoedema of the ONH (the latter does not leak). Pseudoedema is characteristic of Leber hereditary optic neuropathy. Angiography may also demonstrate delayed or absent choroidal filling. This finding may explain vision loss due to choroidal ischemia, which strongly indicates a diagnosis of GCA (Fig 3-7). Indocyanine green (ICG) angiography may facilitate better assessment of choroidal blood flow and reveal deep inflammatory lesions. For further discussion of fluorescein angiography, see BCSC Section 12, Retina and Vitreous.
Lee AG, Brazis PW. Giant cell arteritis. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2005, module 6.
Fundus autofluorescence uses the same excitation and emission filters as fluorescein angiography but does not require injection of a contrast dye. ONH drusen are visible with autofluorescence (Fig 3-8). Lipofuscin, which accumulates in higher amounts in damaged retinal pigment epithelium (RPE) cells, causes hyperfluorescence. This is seen in some retinal pathologies, such as multiple evanescent white dot syndrome (MEWDS), acute macular neuroretinopathy (AMN), acute zonal occult outer retinopathy (AZOOR), and acute idiopathic blind-spot enlargement (AIBSE). Because funduscopic abnormalities in these conditions are often subtle, they are commonly mistaken for an optic neuropathy, which makes fundus autofluorescence a valuable diagnostic tool in this clinical setting.
Figure 3-7 Fluorescein angiography image of a retina exhibiting signs of giant cell arteritis. Normally, the choroid fills completely within 3–5 seconds and before the retinal arteries do. The fluorescein dye appears light in this positive image. The retinal arteries and veins are filled, and the temporal choroid has a large perfusion defect consistent with choroidal ischemia from giant cell arteritis.
(Reprinted with permission from Lee AG, Brazis PW. Giant cell arteritis. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2005, module 6. Cover image.)
Figure 3-8 Investigation for idiopathic intracranial hypertension. A, ONH photograph demonstrates blurring of the ONH margins with elevation, suggesting possibly bilateral ONH swelling (ie, papilledema). B, ONH drusen are visible with fundus autofluorescence, consistent with pseudopapilledema.
(Courtesy of Helen V. Danesh-Meyer, MD.)
Optical coherence tomography
Optical coherence tomography (OCT) provides noninvasive, high-resolution, in situ visualization of the retinal layers and ONH. OCT can be very helpful in the evaluation and management of certain neuro-ophthalmic conditions. OCT is useful for structural measurement of peripapillary RNFL thickness, volumetric analysis of the ONH, and evaluation of macular anatomy. The measurement of the RNFL thickness provides indirect information regarding the axonal integrity of the optic nerve. In several optic neuropathies, the degree and the site of RNFL thinning correlate with the threshold sensitivity of the corresponding area of the visual field (Figs 3-9, 3-10).
OCT predicts the potential for visual recovery after surgery in patients with compressive chiasmal tumors. Patients who have significant visual field defects but preserved RNFL thickness (the threshold is approximately 75 μm but depends on age) typically recover excellently, irrespective of the degree of preoperative vision loss.
Figure 3-9 Superior sectoral ONH pallor following nonarteritic anterior ischemic optic neuropathy, right eye. A, ONH photograph. B, The corresponding static automated perimetry demonstrates an inferior scotoma. C, Optical coherence tomography (OCT) demonstrates superior RNFL thinning.
(Courtesy of Helen V. Danesh-Meyer, MD.)
Figure 3-10 Pituitary adenoma with bitemporal visual field loss. OCT demonstrates nasal and temporal thinning of the retinal nerve fiber layer (RNFL) (A), which corresponds to the clinical appearance of horizontal band atrophy (B).
(Courtesy of Helen V. Danesh-Meyer, MD.)
Automatic segmentation of the macula on OCT allows measurement of the inner retina (RNFL, ganglion cell layer, and inner plexiform layers), referred to as the ganglion cell complex (GCC). In patients with multiple sclerosis (MS) or other optic neuropathies, GCC thickness better correlates with visual acuity and quality of life than does RNFL thickness.
Macular cube OCT and macular line scans can help identify occult retinal pathology that mimics optic nerve disease. For example, subretinal fluid from central serous retinopathy may be mistaken for optic neuritis. MEWDS, AZOOR, and AMN can be detected with OCT owing to the disruption of the inner and outer segments of the retina (Fig 3-11).
OCT also has a role in monitoring disease progression. As in glaucoma, the RNFL thickness can be monitored over time in patients with chronic diseases such as MS and compressive optic neuropathy to quantify axonal loss (Fig 3-12).
A clinical challenge often encountered in neuro-ophthalmology is differentiation among anomalous optic nerves, ONH drusen, and papilledema. Several OCT features may suggest the diagnosis; however, OCT currently cannot definitively distinguish mild papilledema from an anomalous, crowded ONH or buried ONH drusen.
Figure 3-11 Acute macular neuroretinopathy (AMN) in a 16-year-old male who presented with vision loss in both eyes. A, Fundus photographs reveal mild macular changes. B, Corresponding macular OCT line scans demonstrate the focal area of disruption (brackets) of the ellipsoid zone (arrows) in the nasal macula of each eye. These changes decrease with time.
(Reprinted with permission from Sitko KR, Athappilly G, Hedges TR III. Ancillary testing in neuro-ophthalmology. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2015, module 1.)
Figure 3-12 Evaluation of a patient with a pituitary tumor. A, Bilateral ONH pallor. B, The preoperative visual field demonstrates bitemporal hemianopia. C, OCT shows minor nasal thinning on the right, with a normal average RNFL thickness of 99 μm. The left shows generalized thinning, with disproportionate thinning nasally and temporally, and an average thickness of 67 μm. The thin RNFL on the left (because it is <75 μm) suggests a poor recovery, while a normal preoperative RNFL suggests significant recovery of visual field to normal/near-normal levels. D, The postoperative visual field defect shows near-normal resolution of the temporal visual field on the right and persistent temporal defect on the left.
(Courtesy of Helen V. Danesh-Meyer, MD.)
OCT has limitations. Many of the abnormalities seen on OCT are not specific to a particular disease process. For example, thinning of the RNFL occurs with any optic neuropathy. RNFL loss plateaus around 40–50 μm; further loss is undetectable. The wide variability in RNFL values means that some patients have statistically abnormal results that are in fact normal for them. See BCSC Section 10, Glaucoma, and Section 12, Retina and Vitreous, for more information.
Kardon RH. Role of the macular optical coherence tomography scan in neuro-ophthalmology. J Neuroophthalmol. 2011;31(4):353–361.
Mendoza-Santiesteban CE, Gonzalez-Garcia A, Hedges TR III, et al. Optical coherence tomography for neuro-ophthalmologic diagnoses. Semin Ophthalmol. 2010;25(4):144–154.
Ultrasonography is useful in diagnosing buried ONH drusen, which are hyperechoic on B-scan. Ultrasonography is more sensitive for ONH drusen than is autofluorescence or computed tomography. Ultrasound is also helpful in diagnosing scleritis, which can mimic optic neuritis. Patients with papilledema can have a positive 30° test, in which the diameter of the optic nerve sheath decreases when the patient is asked to fixate 30° away from primary gaze.
When the patient has central or peripheral vision loss but no obvious fundus abnormality, ancillary electrophysiologic testing may help confirm or rule out occult abnormalities of the optic nerve or retinal function. See BCSC Section 12, Retina and Vitreous.
Visual evoked potential testing
Visual evoked potential (VEP) testing measures electrical signals produced in response to a visual stimulus; the signals are recorded at the scalp overlying the occipital cortex. Damage anywhere along the afferent visual pathway can reduce the amplitude or speed of the signal. Because the central visual field predominates in the occipital cortex, isolated peripheral vision loss may yield normal VEP results.
The most common stimulus used for VEP testing is a checkerboard target with a pattern that reverses every half-second. The pattern size may also vary, with smaller pattern sizes allowing detection of smaller changes in function. If patients with poor vision cannot easily see a pattern stimulus, a flash stimulus may be used instead. The response from the checkerboard pattern provides a more quantifiable and reliable VEP waveform.
The most common wave measured in VEP testing is the P100 wave, which occurs 100 milliseconds after stimulus onset in patients with normal vision. The P100 latency and, to a lesser degree, the amplitude are the most useful features analyzed. Demyelination has a greater effect on the latency of the P100 waveform than on its amplitude. Ischemic, compressive, or toxic optic nerve damage primarily reduces amplitude, with less effect on latency. A normal VEP (especially in response to a checkerboard pattern stimulus with a high spatial frequency) is evidence for a nonorganic etiology in a patient who reports severe vision loss. However, an abnormal VEP does not prove pathology.
The VEP test has significant limitations. It is subject to influence by numerous factors that may produce abnormal waveforms despite normal visual pathways, including uncorrected refractive error, media opacities, amblyopia, fatigue, and inattention (intentional or unintentional). Although an abnormal VEP may indicate visual pathway dysfunction, the differential effects on latency versus amplitude may not be sensitive or specific enough to narrow the differential diagnosis. The VEP is clinically useful in 2 situations: (1) evaluation of the visual pathway in an inarticulate patient and (2) confirmation of intact visual pathways in a patient with suspected nonorganic disease. A consistently abnormal flash response in an infant or inarticulate adult reflects gross impairment. An abnormal pattern response may indicate damage or may be a false-negative result for the reasons just cited. Normal responses confirm intact visual pathways.
Odom JV, Bach M, Brigell M, et al; International Society for Clinical Electrophysiology of Vision. ISCEV standard for clinical visual evoked potentials: (2016 update). Doc Ophthalmol. 2016;133(1):1–9.
The electroretinogram (ERG) measures the electrical activity of the retina in response to various light stimuli under different states of light adaptation. Electrical activity is measured at the corneal surface by electrodes embedded in a corneal contact lens worn for testing.
The full-field ERG response is generated by stimulating the entire retina with a light source under varying conditions of retinal adaptation. Major components of the electrical waveform that are generated and measured include the a-wave, derived primarily from the photoreceptor layer; the b-wave, derived from the inner retina, probably Müller and on-bipolar cells; and the c-wave, derived from the RPE and photoreceptors. The examiner can separate rod and cone photoreceptor responses by varying the stimuli and the state of retinal adaptation during testing.
The ERG is useful in detecting diffuse retinal disease in cases of generalized or peripheral vision loss. Disorders such as retinitis pigmentosa (including the forms without pigmentation), cone–rod dystrophy, toxic retinopathies, and the retinal paraneoplastic syndromes (cancer-associated retinopathy [CAR]) and melanoma-associated retinopathy [MAR]) may present with variably severe vision loss and minimal visible ocular abnormality. Invariably, the ERG pattern is severely depressed by the time substantial vision loss has occurred, and thus testing is extremely useful. The full-field test, however, measures only a mass response of the entire retina; minor or localized retinal disease, particularly maculopathy, even with severe visual acuity loss, might not produce an abnormal response.
The multifocal ERG (mfERG) simultaneously records and topographically maps ERG signals from up to 250 focal retinal locations within the central 30° (Fig 3-13). Because it is a light-adapted test, an mfERG tests the cone system. Further, because it does not rely on a mass retinal response, as does a full-field ERG, an mfERG is very useful in detecting occult focal retinal abnormalities, especially early cone and cone–rod dystrophies. This technique can differentiate optic nerve from macular disease in occult central vision loss, because the signal generally remains normal in optic nerve disease. Also, causes of outer retinal degeneration, such as MEWDS, AIBSE, and AZOOR, result in changes in the mfERG. See BCSC Section 12, Retina and Vitreous.
Figure 3-13 Multifocal electroretinogram response of a patient with maculopathy. The pattern of the affected eye (A) shows flattening of the foveal waveforms compared with that of the unaffected eye (B).
(Courtesy of Anthony C. Arnold, MD.)
Holder GE, Gale RP, Acheson JF, Robson AG. Electrodiagnostic assessment in optic nerve disease. Curr Opin Neurol. 2009;22(1):3–10.
Hood DC, Odel JG, Chen CS, Winn BJ. The multifocal electroretinogram. J Neuroophthalmol. 2003;23(3):225–235.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.