Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

function without altering vital signs, but vomiting and hyperactivity may occur during induction. Recording valid, interpretable pattern reversal VEP responses is possible under chloral hydrate sedation (42). Propofol (Diprivan ) is an intravenous sedative–hypnotic agent that can be titrated to provide different levels of sedation or anesthesia and has the advantage of rapid, predictable awakening (Fig. 6.3). Diazepam and chlordiazepoxide may also be used but are not typically given to young infants. Inhalation anesthetics such as halothane, methoxyflurane, enflurane, diethylether, and chloroform require tracheal intubation and retard retinal dark adaptation (43–46). The deeper anesthesia provided by these anesthetic agents is seldom necessary for visual electrophysiologic recording.

ESTIMATING VISUAL ACUITY IN INFANTS

Preferential-looking behavior and VEP are the two primary methods of estimating visual acuity in infants and preverbal children. The differences between these techniques are outlined in Table 6.1. In the Teller forced-choice preferen- tial-looking technique, pattern stimulus cards, consisting of alternating black-and-white vertical stripes with different strip widths but the same average luminance, are presented to the infant one at the time, either to the right or left of the center in front of a homogenous screen (47). An observer behind the peephole of the background screen determines the location of the grating stimulus and based on the infant’s viewing behavior records the percent correct for each strip width. The visual acuity is estimated from the stimulus with the narrowest strip width, that is, the highest spatial frequency, that consistently elicits the preferential-looking behavior. Estimate of monocular visual acuity is obtained with one eye patched.

VEP estimates of visual acuity in preverbal children may be obtained primarily by two methods: transient responses to pattern reversal stimuli or steady-state responses using specialized techniques such as sweep VEP. In both methods,

recording is made with the child sitting on parent’s lap and in a dark room where the only visual stimulus is the monitor displaying the black-and-white stimulus. One recording electrode is placed at the midline occipital position (Oz) and more recording electrodes may be placed at other occipital positions if desired. An observer behind the monitor starts the recording with a hand-held switch when the child looks into the stimulus and stops the recording when fixation is inadequate or when head movement is excessive.

In estimating visual acuity from pattern reversal VEP, responses to a reversing black-and-white checkerboard stimulus of various check sizes are obtained (48,49). The results are analyzed graphically by plotting the stimulus check sizes against the corresponding amplitudes of the P1 component of the responses. Visual acuity is estimated from the smallest check that corresponds to zero or noise level amplitude based on extrapolating the best-fit curve (Fig. 6.4, Table 6.2). Similar to other pattern reversal VEP recordings, averaging of multiple responses is obtained to improve response-to-noise ratio. Binocular testing is usually performed first followed by monocular testing. Children older than age 6 months with normal visual acuity of 20=20 should produce a detectable response to 15 min of arc checks. For infants younger than age 6 months, optimal check sizes for eliciting VEP responses are larger, 120–240 min of arc for age 1 month, 60–120 min of arc for age 2 months, and 30–60 min of arc for age 3–5 months. Initially, the child is tested with these corresponding agerelated check sizes, and if no detectable responses are obtained, the check size is doubled until there is a detectable response. If no detectable responses are obtained even with large checks, a flash VEP is performed to see if there is any response. After obtaining a binocular response, monocular testing is performed with the other eye patched, and the procedure is repeated starting with the smallest check size that elicited the binocular response.

In estimating visual acuity from sweep VEP, VEP activity to a varying stimulus lasting several seconds is obtained (50–52). The stimulus usually consists of vertically oriented alternating black-and-white stripes, and the width of the

in cycles per degree against the corresponding VEP amplitudes (Fig. 6.5, Table 6.2). Visual acuity is estimated from the narrowest stripe, the one with the highest spatial frequency, that produces no or background noise level amplitude based on extrapolating of the graph. The level of estimated visual acuity is similar for a rate of stimulus reversal between 8 and 24 reversals per second, that is, 8–24 Hz of temporal frequency (51).

Reported success rates of preferential-looking testing in infants and young children vary from about 60% to nearly 100% (53–55). Likewise, reported success rates of VEP acuity testing vary from about 60% to 90% (53,54). These rate variations among studies are likely due to differences in patient population and methodology. In addition, patients with significant motor dysfunction or neurologic developmental delay may be unable to reliably perform preferential-looking testing, and patients with nystagmus or marked abnormal EEG may not be able to provide adequate recorded VEP responses.

Visual acuity estimates from forced-choice preferential looking are generally worse than those estimated from VEP (56,57). In normal controls, VEP acuity estimates indicate rapid acuity improvement after birth with a Snellen equivalent acuity of near 20=20 attained by age 6 months. In contrast,

Figure 6.4 (Facing page) Estimating visual acuity in infants with pattern reversal VEP. The amplitudes of the pattern reversal VEP responses for stimulus of different check sizes are shown for two infants. Regression lines are fit to the data points shown by the closed circles; data shown by open circles are not included in the regression line analysis but are shown to demonstrate where the peak VEP amplitude occurs. For subject 1, the peak VEP shifts from check size 240 at age 3 months to check size 120 at age 5 months. For age 3 months, extrapolation of the regression line to 0 mV reveals a value of 50, equivalent to visual acuity of 20=100, and for age 5 months, the extrapolated regression line shows a value of 1.50, equivalent to 20=30. For subject 2, the peak VEP is 300 for age 3 months and 150 for age 6 months. Extrapolation of the regression line to 0 mV reveals visual acuity equivalent of 20=80 and 20=20 at age 3 months and age 6 months, respectively. (From Ref. 49 with permission from Elsevier.)

preferential-looking acuity estimates demonstrate a Snellen equivalent of 20=50 by age 1 year followed by improvement to 20=20 by about age 4 years (58). The rate of development is steeper for Teller preferential-looking acuity than sweep VEP acuity with Teller preferential-looking acuity starting at a much lower level (57). Differences in Snellen equivalent acuity between preferential-looking and VEP estimates are due to the fact that each test provides different information about the visual system (Table 6.1). Preferential-looking acuity tests functional or behavioral acuity while VEP acuity reflects potential acuity measured at the visual cortex. In addition, the magnitude of differences between clinical recognition Snellen acuity and preferential-looking acuity or VEP acuity depends on the ocular condition (53). For example, preferential-looking grating acuities are similar to clinical recognition Snellen acuities in normal children, but preferential-looking acuities are better than recognition acuities among patients with an abnormal fovea such as oculocutaneous albinism, macular coloboma, and persistent hyperplastic primary vitreous (55).

AMBLYOPIA

Amblyopia is a developmental anomaly that usually produces impaired visual function in one eye although binocular involvement may also occur. The condition is the result of persistent blurred image from one or both eyes during visual development due to anisometropia, strabismus, or visual deprivation from cataract, corneal opacity, or ptosis. The cellular layers of the visual cortex normally receive binocular projections from corresponding visual field areas, but in amblyopia, the projections are predominantly monocular from the non-amblyopic eye. Amblyopia develops during the first 3 years of life and responds more favorably if treatment is instituted before age 6 years. In young children, treatment of the underlying cause as well as a regimen of part-time or full-time occlusion of the non-amblyopic eye should be initiated as soon as amblyopia is identified.

The most prominent feature of amblyopia is a reduction in visual acuity, but amblyopic deficits are numerous and include impaired contrast sensitivity and stereoacuity. In preverbal children, amblyopia is commonly diagnosed by determining fixation pattern or by estimating visual acuity using either the Teller preferential-looking technique or VEP. In assessing fixation pattern, the inability to maintain fixation with one eye or the other while the opposite eye is covered suggests a fixation preference and is an indication of reduced visual acuity. Other methods of estimating visual acuity such as Teller preferential-looking technique, pattern reversal VEP, and sweep VEP are discussed in detail earlier in this chapter.

Several studies have demonstrated improved pattern reversal VEP P100 amplitude and implicit time in the amblyopic eye with contralateral monocular occlusion treatment (59–61). Although the P100 latencies of the pattern VEP are prolonged in amblyopic eyes, the latencies of the second positive component may be shorter than normal eyes, perhaps as a reflection of selective loss of the contrast-specific evoked potential mechanism (54,62). Multifocal VEP in amblyopic eyes shows greater deficits at the fovea and greater impairment in the temporal field than the nasal field in esotropic amblyopes (63). Some strabismic amblyopes but not anisometropic amblyopes may have supranormal flash VEP response at higher temporal frequencies (64).

The binocularity of the visual cortex may be assessed by a specialized VEP technique called the binocular beat technique (65). In this technique, the stimulus consists of two uniform fields whose luminances are modulating sinusoidally at different temporal frequencies. During testing, one field is seen by one eye while the other field is seen by the other eye. The two luminance modulating fields have different frequencies and come in and out of phase with each other so that the monocular signals summate and cancel each other at the visual cortex. Steady-state VEP of normal subjects shows a modulating waveform response with a frequency (beat frequency) corresponding to the arithmetic difference between the two frequencies of the stimulus fields. In subjects with

binocular vision deficits such as those with amblyopia, the VEP beat response is severely reduced (66–68).

Full-field ERG responses are normal in amblyopic eyes, and EOG responses are mildly reduced (69). The amount of EOG amplitude reduction is very modest and its clinical significance is doubtful since the light-peak to dark-trough amplitude ratio is unaffected compared to the contralateral eye. Studies of pattern ERG responses in amblyopia are conflicting. Some studies showed mild decreases of the P50 component (70,71) while other studies found no pattern ERG abnormalities (72,73).

AGING

Gradual decline of visual function and electrophysiologic responses in the absence of any recognizable disease such as cataract or retinal degeneration is a normal part of aging and is the result of age-related physiologic changes of the neuronal visual pathway, ocular media, and pupil size. Therefore, ideally, each laboratory should obtain age-related normative values for each electrophysiologic test to facilitate clinical interpretation.

Aging Effects on Full-Field ERG

The amplitudes and implicit times of virtually all components of the full-field ERG worsen with aging (Fig. 6.1) (74–81). Although a gradual decline begins not long after ERG maturation, age-dependent changes are generally less likely to be clinically significant until after about age 50 years. In a study of standard full-field ERG in 268 normal subjects, Birch and Anderson (12) found the logarithm of the rod and cone amplitudes decreased exponentially with age in adults such that the amplitudes for rod and cone responses declined to one half those in the young adult level by about age 70 (Fig. 6.6). The decline in amplitude was gradual from ages 5 to 54 years and was followed by a rapid decline beyond age 55 years. The amplitudes were converted to logarithm values for analysis, because the distributions of the full-field ERG