Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

Figure 17.2 Multifocal VEP of a patient with glaucoma (right eye). Note the area of decreased VEP responses inferiorly (grey area) related to glaucomatous damage. (From Ref. 141 with permission from the American Medical Association.)

been reported in glaucoma but they are unlikely to be clinically significant (33). However, the optic nerve head component of the multifocal ERG can be extracted and is decreased in glaucoma but its utility requires further investigation (Fig. 17.4).

Optic Neuritis=Multiple Sclerosis

Inflammation of the optic nerve or optic neuritis is associated with a variety of disorders including multiple sclerosis, neuromyelitis optica, sarcoidosis, syphilis, human immunodeficiency virus (HIV) infection, lyme disease, and sinus disease. When the anterior portion of the optic nerve is involved, edema of the optic nerve head is evident. If the involvement is further posterior, the term ‘‘retrobulbar’’ optic neuritis is used, and the optic nerve head appears normal.

Figure 17.3 Full-field ERG intensity series for a 63-year-old patient with primary open-angle glaucoma demonstrating reduced photopic negative response (PhNR). The recordings were made with a brief (<6 msec) red stimulus on a rod saturating (3.7 log scotopic troland) blue background. (From Ref. 32 with permission of Investigative Ophthalmology and Visual Science.)

With time, various degree of optic nerve pallor develops depending on the amount of damage. Symptoms and signs of optic neuritis include decreased vision over days, periocular pain, impaired color perception, visual field defect, and afferent pupillary defect. Severity is highly variable, and visual acuity ranges from 20=20 to no light perception.

The most common type of optic neuritis is acute demyelinating optic neuritis associated with multiple sclerosis, which typically affects young adults of age less than 50. Patients with greater numbers of demyelinating lesions on brain MRI are at higher risk of developing multiple sclerosis. Visual prognosis is generally favorable with most patients recovering to 20=25 or better over 7 weeks or longer. Treatment with intravenous methylprednisolone during the acute phase of optic neuritis hastens visual recovery and delays the development of multiple sclerosis. Chronic use of immunomodulating agents such as beta-interferon 1a (Avonex) helps to reduce future multiple sclerosis attacks.

Figure 17.4 The multifocal ERG optic nerve head component (ONHC) of a patient with primary open-angle glaucoma (POAG). The first-order traces of the multifocal ERG are obtained with a sequence of all-black, all-white, and all-black stimulus frames inserted between each of the multifocal stimulus presentations. The traces are then separated into the retinal component (not shown) and the ONHC. The normal ONHC tracings are more delay for hexagons further away from the optic nerve head. Note greater ONHC impairment of the superior hexagons 3, 4, and 5 corresponding to the superior visual field loss. (From Ref. 142 with permission of Investigative Ophthalmology and Visual Science.)

The VEP serves as a complementary visual function test in optic neuritis and is particularly useful when visual acuity, visual field, and afferent pupillary defect testing are equivocal (Fig. 17.5). Numerous studies have demonstrated reduced and delayed VEP in optic neuritis (34–37). The VEP elicited with chromatic stimulus is more impaired in optic neuritis than standard VEP (37). Pattern VEP latency and amplitude correlate with other clinical parameters such as visual acuity and field and improve with optic neuritis recovery (38,39). In some cases, VEP may detect subclinical impairment that are not apparent on visual acuity and field testing (38–40). For instance, VEP delays may occur in multiple sclerosis patients

Figure 17.5 Pattern-reversal VEP in a 41-year-old patient with multiple sclerosis. The patient reported abnormal vision of the left eye despite 20=20 visual acuity in each eye along with normal visual fields and normal optic nerve head appearance. The prolonged P100 of the left eye suggests that the patient may have had mild optic neuritis in the left eye.

who never had clinical optic neuritis and are common in the fellow ‘‘unaffected’’ eye of patients with unilateral optic neuritis (37,41). The VEP delays remain in most patients with resolved optic neuritis (42). In general, most studies indicate that delayed VEP is a risk factor for developing clinical definite multiple sclerosis (43–47). Accordingly, the International Panel on the Diagnosis of Multiple Sclerosis recommends that multiple sclerosis be diagnosed on the basis of not only clinical course but also by the use of objective tests such as MRI, cerebrospinal fluid analysis, and VEP (48,49). For example, in patients with insidious neurological progression but no neurologic episodic attacks, the diagnosis of multiple sclerosis may be determined by positive cerebrospinal fluid findings and

delayed VEP responses in association with the number of demyelinating MRI lesions (49). Of interest, multifocal VEP is a new tool that can be used to track local optic nerve damage after unilateral optic neuritis (28).

Several studies have documented impaired pattern ERG responses in optic neuritis (34,50,51). The N95 component of the pattern ERG reflects retinal ganglion cell function and is impaired in optic neuritis. The P50 component of the pattern ERG is generated by both retinal ganglion cells and by other intraretinal cellular elements and is relatively preserved in optic neuritis (52). However, P50 may be marked reduced during the acute phase of optic neuritis and recover over weeks (53,54). In a study of 200 eyes with optic neuritis, Holder (54) found abnormal pattern ERG in 40% of the eyes, and of these, 85% had abnormal N95 component without P50 involvement. A subsequent review of 382 eyes by the same investigator showed greater pattern ERG abnormalities in those eyes with attacks of optic neuritis than those eyes with subclinical demyelination (52). In any case, N95 abnormalities may persist after clinical recovery of optic neuritis and may occur in multiple sclerosis patients who never had clinical optic neuritis (53,55). Aside from abnormalities of the transient pattern ERG, steady-state pattern ERG also demonstrates abnormalities in optic neuritis with impairment of the second harmonic component by Fourier analysis (36,37,55,56).

Ischemic Optic Neuropathy

Ischemia of the optic nerve may occur anteriorly at the optic nerve head or posteriorly in the retrobulbar portion of the optic nerve. Anterior ischemia optic neuropathy (AION) is more common and is caused by hypoperfusion of the posterior ciliary arteries. Criteria for the diagnosis of AION include: (1) an acute decrease in vision; (2) nerve fiber layer defect on visual field testing; (3) relative afferent pupillary defect; and

(4) optic nerve head edema often with hemorrhage during the acute period with progression to optic pallor over weeks. In contrast, posterior ischemic optic neuropathy (PION) is

associated with acute decrease of vision with normal appearance of the optic nerve head followed by the development of optic pallor over weeks. The diagnosis of PION is made on the basis of excluding other disorders and neuroimaging is usually helpful. No established treatment of ischemic optic neuropathy is available, and therapy is aimed at control of risk factors such as hypertension and diabetes. Electrophysiologic testing is not ordinarily performed. Impaired VEP and pattern ERG responses have been documented (27,28,34,57). These impaired responses are non-specific but may serve as complementary tests to determine optic nerve dysfunction especially when other visual function tests or signs of the disease are unreliable or equivocal. In one study, reduction in N95 amplitude of the transient pattern ERG, a measure of retinal ganglion cell response, was found in AION and was suggested as a way to differentiate AION from optic neuritis (58). However, reduced N95 amplitude is also reduced in optic neuritis (51). Clinical multifocal ERG or full-field ERG are unaffected by ischemic optic neuropathy but may help to rule out retinal dysfunction in patients suspected of PION.

Papilledema

Optic nerve head edema due to raised intracranial pressure is typically bilateral and is called papilledema. Intracranial hypertension may be caused by intracranial space-occupying lesion or from idiopathic intracranial hypertension (IIH), traditionally known as pseudotumor cerebri. Prompt neuroimaging is essential in the work-up of papilledema, and if neuroimaging is normal, spinal tap with cerebrospinal fluid pressure measurement is necessary to diagnose IIH. When papilledema is associated with intracranial mass, treatment of the underlying lesion is warranted. In IIH, the papilledema may be treated with medications or if severe, surgically with optic nerve sheath fenestration and ventriculo-peritoneal shunt. Early papilledema produces enlarged blind spot and mild nerve fiber layer field defects, which are reversible with successful therapy. In severe papilledema, hemorrhages and exudates at the optic nerve head are present, and severe

visual field defects and decrease in visual acuity loss are encountered. If unchecked, papilledema can lead to permanent loss of nerve fibers and optic nerve pallor. Electrophysiologic testing is not routinely performed. Impaired VEP and pattern ERG responses may occur before disturbances of visual fields and acuity in IIH patients (59,60). However, in a study of 13 patients with IIH, Sorensen et al. (59) found that although the pattern VEP was significantly delayed compared to 20 normal subjects, only four patients had latencies outside the normal range.

Compression of Optic Nerve or Chiasm

Common compressive disorders of the anterior visual pathway include meningioma, thyroid-associated ophthalmopathy, and pituitary adenoma. The diagnosis is made on the basis of impaired visual function and neuroimaging. In general, impaired visual function is evident on clinical examination and established by the results of visual acuity, color, visual field, and afferent pupillary testing. Effective treatments are usually available and include medication, surgery, and radiation. Electrophysiologic tests are not widely performed. Impaired VEP, pattern ERG, and the PhNR on fullfield ERG in patients with compressive lesion are common, and these tests may serve as additional diagnostic and monitoring tools especially when other visual tests are equivocal or unreliable (50,51,61–65). For instance, flash and pattern VEP are helpful in monitoring compressive optic neuropathy from thyroid-associated ophthalmopathy (66–69). The results of one study suggest that the delay in VEP responses was smaller and less frequent in patients with compression lesion compared to patients with demyelinating disease (61). In keeping with the general principle that the N95 component of the pattern ERG is a measure of retinal ganglion cell function and the P50 component is relatively spared in optic neuropathy, reduced N95 is common in compressive optic neuropathy (52). For instance, in patients with chiasmal compression from pituitary tumors, prognosis for visual improvement is more favorable when the pre-treatment N95:P50 ratio of the

pattern ERG is normal (70). Lastly, the PhNR of the full-field ERG is reduced in patients with optic atrophy induced by compression and show a good correlation with retinal nerve fiber layer thickness on optical coherence tomography (65).

Traumatic Optic Neuropathy

Traumatic injury to the optic nerve may occur from direct penetrating injury caused by objects or, more commonly, from indirect blunt force to the head. The intracanalicular portion of the optic nerve, which is fixed by the bony walls of the optic canal, is most susceptible to traumatic injury. Treatment options include corticosteroid therapy and surgical optic canal decompression but treatment is controversial because evidence is lacking that any treatment is beneficial (71). Prognosis for significant visual improvement is often unfavorable.

In post-trauma patients who are not alert enough for visual function testing and whose pupillary light reflexes are sluggish due to coma or sedation, flash VEP may be helpful in the diagnosis and determining the prognosis of traumatic optic neuropathy (72–75). Attempts have also been made to use flash VEP to determine whether to initiate corticosteroid treatment or to perform surgical decompression, but these treatments remain controversial (76). Pattern ERG responses are also impaired in patients with traumatic optic neuropathy (34,50,51,77), but unlike the flash VEP, steady fixation is required and testing unresponsive patients is not typically feasible. The PhNR of the full-field ERG is also reduced in patients with optic atrophy due to trauma (65).

Optic Nerve Head Drusen

Prognosis of refractile nodules or drusen of the optic nerve head is generally favorable, and the diagnosis is usually made by ultrasound. As a reflection of impaired ganglion cell function, reduced N95 component of the pattern ERG may be found up to nearly 80% of eyes with optic nerve drusen while the P50 component is less likely to be affected (78). Reduced and prolonged VEP responses may also be found (78–80).

Hereditary Optic Neuropathies

Inheritance patterns of hereditary optic neuropathies include autosomal dominant, autosomal recessive, and maternal through mitochondrial DNA. All hereditary optic neuropathies result in bilateral visual loss and optic atrophy, and except in Leber hereditary optic neuropathy, the visual loss is often slow and progressive. The optic neuropathy may occur in isolation or as part of an inherited systemic syndrome. The more common hereditary optic neuropathies include Leber hereditary optic neuropathy and dominant optic atrophy.

Leber hereditary optic neuropathy is caused by mitochondrial DNA mutations with changes at positions 11778, 3460, or 14484, being found in at least 90% of affected persons. Although mitochondrial DNA is inherited maternally, 80–90% of symptomatic persons are male. Some carriers of the mutant mitochondrial DNA, especially females, may never become symptomatic. Symptoms start with acute or subacute painless loss of central vision in one eye followed by the involvement of the second eye usually within weeks to months. Spontaneous visual improvement may occur gradually or suddenly up to 10 years after onset of visual loss. During the acute stage, circumpapillary telangiectatic microangiopathy, swelling of the peripapillary nerve fiber layer, and absence of leakage from the disc or papillary region on fluorescein angiography may occur, but up to 40% of patients may not have any visible abnormalities. Subsequently, optic atrophy develops over weeks. The diagnosis is confirmed by mitochondrial DNA analysis, and electrophysiologic tests are of limited value except when desired for documenting optic nerve dysfunction. In Leber optic neuropathy, full-field ERG is normal and pattern ERG demonstrates reduced N95 with a normal or attenuated P50 indicating retinal ganglion cell dysfunction (52,81). Flash and pattern VEP shows reduced amplitude and increased latency (81–83). Carriers or presymptomatic persons with Leber optic neuropathy may or may not have impaired VEP responses (83–85).

Patients with dominant optic atrophy have progressive central vision loss with developing optic atrophy that

typically begins insidiously in the first decade of life. Multiple genotypes may produce dominant optic atrophy. In OPA1, mutations of the OPA1 gene are found on chromosome 3. Diagnosis of dominant optic atrophy is based on clinical features, family history, and genetic testing. Electrophysiologic findings document optic nerve dysfunction but are nonspecific (86). Pattern ERG reports from a series of 87 patients from 21 pedigrees with dominant optic atrophy showed preferential N95 reduction early in the disease with P50 reduction as the disease progressed (87,88). However, the pattern ERG remained detectable even in advance cases. The VEP responses may be non-detectable in more advanced cases, and when detectable, most VEP responses are mildly to moderately delayed (87,89,90).

CENTRAL NERVOUS SYSTEM DISORDERS

Cortical Blindness

Cortical blindness refers to bilateral dysfunction of the visual pathways anywhere along the lateral geniculate body to the occipital cortex. Because the lesions are not always isolated to the cortex and the degree of visual impairment in cortical blindness is highly variable and rarely complete, the term ‘‘cortical visual impaired’’ has been suggested (91). Cortical visual impairment may be caused by a spectrum of conditions including stroke, infections, neurodegenerative diseases, metabolic and toxic insults, tumors, and trauma.

The diagnosis of cortical visual impairment is made on the basis of ophthalmic examination and abnormal findings on diagnostic tests such as MRI and VEP. If the patient is able to perform visual fields, the homonymous nature of the visual loss may be detected. In some cases, full-field ERG is necessary to rule out occult ocular disorders such as paraneoplastic retinopathy, previous retinal vascular occlusions, achromatopsia, and Leber congenital amaurosis. The VEP is helpful to establish visual pathway dysfunction in cortical visual impairment, and a high correlation between visual acuity and VEP is found in some studies (92,93). Flash VEP