Chapter 187 – Differentiation of Optic Nerve from Retinal Macular Disease
ALFREDO A. SADUN
• Optic nerve disease involves injury of the retinal ganglion cells and hence the axons that constitute the optic nerve, whereas macular disease involves injury to the retina in the fovea and parafoveal areas.
• Optic nerve lesions generally produce an afferent pupillary defect and a severe dyschromatopsia.
• Macular lesions usually cause severe loss of central acuity and metamorphopsia.
• Photostress and electroretinography testing may reveal retinal disease.
• Contrast sensitivity and visually evoked response testing may disclose optic nerve disease.
Optic nerve disease may be severe with profound losses of visual acuity, color vision, and visual field such that the diagnosis is obvious. However, mild optic neuropathies that cause only minimal visual loss may be difficult to diagnose. Optic neuropathies and maculopathies often have overlapping presentations, for example, optic neuritis and central serous retinopathy, both of which can present in a young adult with acute, painless, monocular visual loss. At times the relative absence of fundus findings in patients who have acute visual loss may further frustrate the clinician’s ability to make the correct diagnosis.  Because impairments of vision that result from optic nerve dysfunction may be harbingers of intracranial pathology, which might require neurosurgical intervention, and maculopathies often respond to local treatment, such as laser photocoagulation, the clinician needs to make an early and accurate distinction between an optic neuropathy and a maculopathy.
EPIDEMIOLOGY AND PATHOGENESIS
The most common optic neuropathies in young and older adults are optic neuritis and nonarteritic anterior ischemic optic neuropathy, respectively. Regardless of the nature of the optic neuropathy, the cell that is injured or impaired is the retinal ganglion cell. Once this cell is dead, its axon undergoes anterograde degeneration, resulting in optic atrophy.
Retinal maculopathies may arise from a variety of lesions of the outer or inner retina or choroid and often present somewhat like optic neuropathies.
TABLE 187-1 — DIFFERENTIATION OF OPTIC NERVE FROM MACULAR DISEASE BY HISTORY
Stable, progressive, or transient
Sometimes with eye movements
Description of deficit
Dark or gray cloud
Sometimes toward hyperopia
Loss of visual acuity from optic nerve disease is usually perceived as a sense of generalized dimness, patchy dark spots, or black curtains across the visual field. Optic neuropathies also cause a darkening or desaturation of colors and objects, which may appear to have less contrast to the point of becoming indistinguishable. Patients with optic neuritis may also describe phosphenes with eye movements. Pain is associated with certain optic neuropathies ( Table 187-1 ).
In contradistinction, patients who have maculopathies complain of metamorphopsia in the central visual field. Micropsia is more common than macropsia. Patients who have maculopathies may experience slight photophobia or complain of glare or even dazzle. Instead of objects that appear dim (as in optic neuropathies), patients may complain that objects appear too bright.
DIAGNOSIS AND ANCILLARY TESTING
It is important to elicit from the patient the tempo of the onset and course of symptoms. Optic neuritis usually develops over hours to days, stabilizes, and then shows improvement in the ensuing weeks. Anterior ischemic optic neuropathy causes a sudden loss of vision with very little progression or resolution thereafter.  Maculopathies may be acute or insidious in onset.
Visual acuity is more likely to be affected by macular disease than by diseases of the optic nerve ( Table 187-2 ). Three tests—the measurement of the pupillary response, color vision, and sense of brightness testing —are particularly sensitive to impairments of the optic nerve. A consensual pupillary response that is greater than the direct pupillary response is indicative of an afferent pupillary defect. This is usually judged qualitatively, although Fineberg and Thompson  quantitate it using neutral density filters.
TABLE 187-2 — DIFFERENTIATION OF OPTIC NERVE FROM MACULAR DISEASE BY CLINICAL EXAMINATION
Afferent pupillary defect
Normal or central scotoma
Although color vision is best assessed using a Farnsworth-Munsell 100-hue test, a more convenient option is the shorter, desaturated form of the Farnsworth-Munsell test, the D-15, which requires the alignment of only 15 color caps. An even easier in-office test of color vision involves the use of pseudoisochromatic plates of the A-O or Ishihara type. Disease of the optic nerve invariably produces dyschromatopsia and a subjective loss of color vividness, which may be compared between eyes.
The third sensitive measure of optic neuropathy is a change in brightness sense, which may be estimated subjectively when the patient is asked which eye sees a light as brighter, or quantitated using neutral density filters or brightness-sense spectacles, consisting of two pairs of cross-polarizing filters.
Extensive retinal disease may produce mild abnormalities in color vision, brightness sense, and pupillary response, but this is usually accompanied by marked visual loss.
Fundus examination may disclose optic disc swelling; however, optic disc elevation itself does not produce significant impairment of visual function.  Optic atrophy is generally visualized first about 1 month after acute injury to the nerve. Optic neuropathies may produce diffuse dropout or segmental losses in the nerve fiber layer, and certain lesions can produce slits or rake defects in the nerve fiber layer, which may be seen as early as 1 week after injury to the optic nerve. Sectoral disc edema with flame-shaped hemorrhages (anterior ischemic optic neuropathy), lumps and bumps (optic disc drusen), pathologic cupping (glaucoma), sectoral optic atrophy, secondary optic atrophy, and butterfly optic atrophy are patterns of optic disc change that indicate nerve damage of specific types.
Serous neural retinal or retinal pigment epithelial detachments, retinal edema, vascular abnormalities, and exudates may all be seen by direct or indirect ophthalmoscopy or by stereomicroscopy.
Optic neuropathies may cause a large variety of visual field defects, some of which are specific. For example, toxic or nutritional deficiency optic neuropathies usually cause centrocecal field defects. Diseases of the optic nerve head often produce arcuate or altitudinal field defects.
The visual field defect of a maculopathy is almost invariably a central scotoma with a zone of metamorphopsia that surrounds it.
Tangent visual field testing remains a very effective way to assess the central 20° of visual field and when performed at 6.5?ft (2?m) may make the identification of a small central scotoma much easier. Amsler chart testing provides a very sensitive assessment of the central 10° of visual field  and documents the presence or absence of metamorphopsia, a strong indicator of macular disease.
Several specialized tests are very simple, inexpensive, and easy to perform in the office ( Table 187-3 ). Threshold Amsler chart testing is a method in which the Amsler grid is made far more sensitive. In this approach, the patient wears specialized glasses with cross-polarizers in front of both oculars, which are turned to reduce the patient’s perception so that the Amsler chart is barely discerned.
TABLE 187-3 — DIFFERENTIATION OF OPTIC NERVE FROM MACULAR DISEASE BY SPECIAL TESTS AND LABORATORY STUDIES
Visual evoked response
Large latency delay
Small latency delay
Contrast sensitivity functions
Greatest losses between 6–12 cycles/degree
Greatest losses around 18 cycles/degree
In macular disease a delay usually occurs in the recovery of visual pigments that are bleached by a bright light, but bright light has no effect on optic nerve conduction. Hence, photostress testing may be very helpful in the differentiation between maculopathies and optic nerve disorders. A penlight is used to stress each eye and the recovery time, when compared, is much greater with a maculopathy. Patients who have optic neuropathies show little or no prolongation of this recovery time. Fundus fluorescein angiography may be particularly useful for the characterization of retinal diseases.
The visual evoked response may be used to document optic nerve dysfunction. However, increased latency in the visual evoked response may arise from a variety of other diseases, which include refractive error, a maculopathy, or even feigned visual loss. Nevertheless, the test can be very useful when bilateral disease of the optic nerves makes the diagnosis more difficult or when documentation is desired for medicolegal purposes.
The Pulfrich phenomenon is often elicited in a patient who has unilateral optic nerve conduction block and in whom a latency delay may be noted with visual evoked response. In this test, the patient is asked to observe, with both eyes open, a pendulum that swings in one plane. In the presence of a unilateral conduction delay caused by an optic neuropathy, the patient may have the impression that the pendulum swings through an elliptic arc.
In contrast sensitivity testing, patients are asked to view a series of sinusoidal gratings of different spatial frequencies. Vistech plates may be used. Patients who have optic neuropathies may have deficiencies in the middle to high spatial frequencies; patients who have maculopathies usually have deficiencies only in the highest spatial frequencies.
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