Ординатура / Офтальмология / Английские материалы / Electrophysiology of Vision_Lam_2005

detection of local visual field defects. Invest Ophthalmol Vis Sci 1998; 39:937–950.

22.Klistorner AI, Graham SL. Multifocal pattern VEP perimetry: analysis of sectoral waveforms. Doc Ophthalmol 1999;

98:183–196.

23.Seiple W, Clemens C, Greenstein VC, Holopigian K, Zhang X. The spatial distribution of selective attention assessed using the multifocal visual evoked potential. Vision Res 2002; 42:1513–1521.

24.Goldberg I, Graham SL, Klistorner AI. Multifocal objective perimetry in the detection of glaucomatous field loss. Am J Ophthalmol 2002; 133:29–39.

25.Baitch LW, Levi DM. Binocular beats: psychophysical studies of binocular interaction in normal and stereoblind humans. Vision Res 1989; 29:27–35.

26.Sloper JJ, Garnham C, Gous P, Dyason R, Plunkett D. Reduced binocular beat visual evoked responses and stereoacuity in patients with Duane syndrome. Invest Ophthalmol Vis Sci 2001; 42:2826–2830.

27.Struck MC, Ver Hoeve JN, France TD. Binocular cortical interactions in the monofixation syndrome. J Pediatr Ophthalmol Strabismus 1996; 33:291–297.

28.Stevens JL, Berman JL, Schmeisser ET, Baker RS. Dichoptic luminance beat visual evoked potentials in the assessment of binocularity in children. J Pediatr Ophthalmol Strabismus 1994; 31:368–373.

29.Snowden RJ, Ulrich D, Bach M. Isolation and characteristics of a steady-state visually evoked potential in humans related to the motion of a stimulus. Vision Res 1995; 35:1365–1373.

30.Odom JV, De Smedt E, Van Malderen L, Spileers W. Visual evoked potentials evoked by moving unidimensional noise stimuli: effects of contrast, spatial frequency, active electrode location, reference electrode location, stimulus type. Doc Ophthalmol 1998–1999; 95:315–333.

31.Bach M, Ullrich D. Motion adaptation governs the shape of motion-evoked cortical potentials. Vision Res 1994; 34: 1541–1547.

32.Bach M, Ullrich D. Contrast dependency of motion-onset and pattern-reversal VEPs: interaction of stimulus type, recording site and response component. Vision Res 1997; 37:1845–1849.

33.Gopfert E, Muller R, Breuer D, Greenlee MW. Similarities and dissimilarities between pattern VEPs and motion VEPs. Doc Ophthalmol 1998–1999; 97:67–79.

34.Hoffmann MB, Unsold AS, Bach M. Directional tuning of human motion adaptation as reflected by the motion VEP. Vision Res 2001; 41:2187–2194.

35.Niedeggen M, Wist ER. Characterstics of visual evoked potentials generated by motion coherence onset. Brain Res Cogn Brain Res 1999; 8:95–105.

36.Kubova Z, Kuba M, Spekreijse H, Blakemore C. Contrast dependence of motion-onset and pattern-reversal evoked potential. Vision Res 1995; 35:197–205.

37.McKeefry DJ. The influence of stimulus chromaticity on the isoluminant motion-onset VEP. Vision Res 2002; 42:909–922.

38.Tobimatsu S, Timoda H, Kato M. Parvocellular and magnocellular contributions to visual evoked potentials in humans: stimulation with chromatic and achromatic gratings and apparent motion. J Neurol Sci 1995; 134:73–82.

39.Norcia AM. Abnormal motion processing and binocularity: infantile esotropia as a model system for effects of early interruptions of binocularity. Eye 1996; 10:259–265.

40.Shea SJ, Chandna A, Norcia AM. Oscillatory motion but not pattern reversal elicits monocular motion VEP biases in infantile esotropia. Vision Res 1999; 39:1803–1811.

41.Brosnahan D, Norcia AM, Schor CM, Taylor DG. OKN, perceptual and VEP direction biases in strabismus. Vision Res 1998; 38:2833–2840.

42.Hood DC, Greenstein VC, Odel JG, Zhang X, Ritch R, Liebmann JM, Chen CS, Thienprasiddhi P. Visual field defects and multifocal visual evoked potentials: evidence of a linear relationship. Arch Ophthalmol 2002; 120:1672–1681.

MATURATION

The visual system is not fully developed at birth. The foveal pit is incomplete, and the foveal cone photoreceptors are immature. Myelination of the optic nerve is unfinished, and synapses at the lateral geniculate nucleus and the occipital lobe are underdeveloped. Subsequent development and maturation of the visual system require physiologic maturation and environmental visual stimulation. While studies of maturation of VEP and full-field ERG responses are readily available, similar investigations of focal ERG, multifocal ERG, and pattern ERG are more limited in young patients because of difficulty in maintaining required fixation. Obtaining EOG is also difficult in young patients because of the cooperation needed to perform voluntary eye movements.

Maturation of ERG

Full-field cone and rod ERG responses are small and prolonged but detectable after birth for term newborns as well as for preterm infants as young as 30 weeks after conception (Fig. 6.1) (1–11). However, the retinal luminance of the standard ERG as recommended by the International Society for Clinical Electrophysiology of Vision (ISCEV) is too low to reliably elicit responses at birth (12). A quarter of normal infants 5 weeks and younger have no detectable ISCEV standard rod response, and the lower limits of normal b-wave amplitudes for the ISCEV standard rod response as well as for the combined rod–cone response and the cone response include zero until age 15 weeks (7). Therefore, higher intensity stimuli are required to elicit responses reliably in young infants. A retinal illuminance of approximately 2.0 log units higher than the recommended standard flash is necessary to elicit a rod response in virtually all infants at 36 weeks after conception to produce a mean amplitude of 14 mV (1).

Full-field ERG amplitudes and implicit times improve most rapidly during the first 4 months of life followed by slower development thereafter (Fig. 6.1). In general, mean ERG parameters enter the low range of adult values by age

Figure 6.1 Examples of standard ERG responses demonstrating the effects of maturation and aging. (From Ref. 12 with permission from the American Medical Association.)

6 months and approach mean adult values by age 1 year (7,13). However, the ERG components develop at different rates (14). Cone photoreceptors mature earlier than rod photoreceptors. At age 3 months, the maximal scotopic b-wave response (Vmax) and the semisaturation sensitivity constant, log K (the light intensity which elicits half of the maximal response) are about half those of adults (13,15). Likewise, phototransduction of the rod photoreceptors as studied by scotopic high-intensity stimuli and analyses of the leading edge of the a-wave demonstrate sensitivity (S) and maximum responses (Rmp3) reaching half of adult values at about age 9 and 14 weeks, respectively (16). In contrast, rod-mediated parafoveal visual sensitivity does not reach 50% adult value until about 19 weeks (13). However, by age 26 weeks, sensitivity (S) reaches adult value, and rod sensitivity is the same for parafoveal and peripheral retinal regions as in adults (17). Under standard ISCEV conditions, the implicit times of the

combined rod–cone response and cone response decrease with age in infancy but the implicit time of the rod response varies little with age (7).

Maturation of Pattern ERG

Maturation studies of pattern ERG in infants are somewhat limited because of required fixation for pattern ERG recording (18–20). Developmental changes are particularly pronounced during the first 8 weeks after birth with the peak latency of the pattern ERG approaching adult values at about age 6 months (19). For children between age 7 and 18 years, an increasing predominance of the macular contribution seems to occur (20).

Maturation of EOG

The maturation of EOG is difficult to study in infants due to required accurate eye movements. However, EOG can be recorded by eliciting passive eye movements related to the oculo-vestibular reflex (21,22). The infant is placed in the supine position held by the mother in a rocking chair, and a distracting visual stimulus encourages fixation from the infant while the infant is being nursed and rocked. EOG studies indicate that EOG light-peak to dark-trough amplitude ratios of infants are comparable to adult values.

Maturation of VEP

Both flash and pattern reversal VEP responses are small and very prolonged with P1 latency of over 200 msec at birth for term newborns as well as for preterm infants as young as 30 weeks after conception (6,23). VEP latencies shorten rapidly in a logarithmic fashion during the first 6 months of life and essentially reach adult values by age 1 year (Fig. 6.2) (24–26). The rates of improvement of pattern reversal VEP responses are similar for large and small check sizes with responses to small check sizes having longer latencies. In addition, monocular pattern reversal VEP responses have slightly longer latencies than binocular responses with this difference being invariant with age but significantly greater

with larger check stimuli (24). For preterm infants, the maturation of pattern reversal VEP is related more to their gestational or corrected age rather than their postnatal age (27,28). In addition, for normal infants, some specialized VEP responses such as those to pattern chromatic stimuli may not reach adult waveforms until well into childhood (29).

DELAYED VISUAL MATURATION

Delayed visual maturation refers to an idiopathic disorder characterized by visual inattention during infancy. The diagnosis is made by excluding any recognizable ophthalmic or neurologic conditions that impair visual development (30). Infants with delayed visual maturation may frequently demonstrate other signs of delayed neurological development, but the prognosis is generally excellent if visual impairment is the presenting feature (31). Visual behavior develops usually by age 1 year or less, and normal visual function is obtained later in childhood. Diagnostic tests that are beneficial in establishing the diagnosis of delayed visual maturation include magnetic resonance imaging, full-field ERG, and VEP. Full-field ERG is helpful to exclude conditions such as Leber congenital amaurosis and achromatopsia. VEP responses are variable. Several studies have shown reduced or delayed flash and pattern reversal VEP responses in affected infants, which normalize over time (32–35). However, in a study by Lambert et al. (36), eight of nine infants with delayed visual maturation consistently demonstrated normal VEP responses comparable to agematched controls. Differences in study results are likely due to differences in methodology and patient population as well as the fact that variability in VEP responses is high among infants during early development, necessitating the use of adequate age-matched control.

ELECTROPHYSIOLOGIC TESTING IN INFANTS

Recording visual electrophysiologic responses from infants and young children present special challenges (37,38). Their

attention span is short and they do not want to hold still. Crying is a common reaction to situations that they do not understand. Explaining the purpose and procedure of the test to the parents is critical to assure parents that their child will be handled gently and to alleviate any anxieties. The goal is to create a quiet, calm environment devoid of any unnecessary distractions and to minimize the recording period (39). The mother or the person best in calming the child should accompany the child during testing. Deferring bottle feeding for an infant until test time may calm the infant enough for testing, and the use of soft background music will work in some infants. However, gentle restraints may be required in some cases, and even in the best of hands, sedation with pharmacologic agent may be necessary at times. In general, infants and young children are more likely to tolerate recording of responses from only one eye at a time and may not cooperate long enough for successful recordings from both eyes. The use of a hand-held rather than a desk-top full-field stimulus for full-field ERG and flash VEP recordings may be helpful. Recording artifacts from blink, eye, and head movements are frequent in this age group, which necessitate multiple recordings of the same stimulus until repeatable responses are obtained, or averaging of multiple responses may be used to reduce the effect of artifacts. Cooperation notably improves beyond age 5 years, and testing becomes easier in school-age children.

Recording electrophysiologic responses from infants and young children under pharmacologic sedation reduces recording time by quieting the child and minimizing blink, eye, or head movement artifacts and allows full-field ERG and flash VEP recordings. Because of the small risk of life-threatening complications of sedation, participation of an anesthesiologist and strict adherence to hospital guidelines are essential. Virtually all sedative agents are likely to cause some effect on visual electrophysiologic responses, and to facilitate interpretation, each laboratory should ideally obtain agerelated normative electrophysiologic values for the specific sedative agent used. However, realistically, obtaining electrophysiologic values from normal healthy infants or young