electrophysiologic testing and its - Europe PMC

ELECTROPHYSIOLOGIC TESTING AND ITS SPECIFIC APPLICATION IN UNSEDATED CHILDREN BY Thomas D. France, MD INTRODUCTION

ELECTROPHYSIOLO(GIC TESTING INCLUDING THE ELECTRORETINOGRAM (ERG) AND

visual evoked response (VER) may be of great help in diagnosing visual probleims in children. Ophthalmic assessment in infants and ouIlg children, as well as in retarded older children, may not result in a definite diagnosis based on the purely objective nature of the evaluation required in such patients. The most important question may be, Can this child see? A lack of visual attention during the examination may be strong evidence of blindness but may also be indicative of the state of awareness of the child to external stimulation. If there is no obvious cause for visual loss, this question has usually been unanswered until the child is old enough to give a subjective response. In some cases this has led to several years of missed diagnoses, with the resultant frustration of both parents and physician over the proper course of action and the prognosis for the child. The use of ERG/VER testing in such patients has been shown to enhance the ability of the ophthalmologist to reach a definitive diagnosis, especially when primary retinal disease (eg, Leber's congenital amaurosis) or visual cortical disease is present.1 In uncooperative patients the use of sedation or general anesthesia has been advocated to record ERGs using corneal electrodes. Deep general anesthesia, unfortunately, will reduce or ablate the VER and cannot be expected to produce a consistenit response owing to variable anesthetic depths. In addition, the use of potentially dangerous general anesthesia, especially in children with systemic cardiovascular or other defects, to measure ERG/VERi may reduce the feasibility of such testing for most ophthalmologists. The purpose of this thesis is to report a technique that uses skin electrodes to record ERG and VER and allows measurement of these TR. ANu. OPHTH. Soc. vol. LXXXII, 1984

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parameters without the use of sedation. A series of 302 patients have been examined with this techni(ue.

PRINCIPLES OF ELECTRORETINOGRAPHY

Although the ERG was first discovered in animilals by Du Bois-Revmoind in 18492 andl in huImaIns by Dewar in 1877, 3 clinical ERG testing did not become feasible until 1941, wheni Riggs4 developed a cointact lens electrode. Important contributions to the uncderstanding of the various components of the ERG appeared from the laboratory of Granit,' aind the clinical usefulnes of the ERG became most apparent after the pioneering work of Karpef in Sweden in 1945. The ERG can be defined most simply as the record of the transient electrical response produced by the retina following light stimulation. Clinically, the response is usuallv elicited Lb a stroboscope, the intensity, wavelength, and stimulus frequency of which can be easily varied. A contact lens electrode is placed on the anesthetized corinea and the lids are held apart during the testing by the flanged edges of the electrode. The electrical potential between the cornea and a relatively indifferent reference point, usually the forehead, is recorded; it is then amplified and displayed on either an oscilloscope or a printer. Recently, Arden and co-workers' suggested the use of a gold foil electrode, whch is much more easily tolerated by patients. The foil is allowed to rest between the lid and the globe and is easily maintained without local anesthetic. The gold foil electrode has been found to be useful in the detection of pattern-evoked ERGs. Its usefulness in children, however, is somewhat limited in that it does not allow much freedom of movement. In 1908, Einthovein and Jollyv named the various comiiponient waves of the ERG. Thev called the first small negative wave the "a-wave," the large, rapid positive wave the "b-wave," anid the slowly rising positive response the "c-wave." These waves appear when the light stimulus is turned on. A fourth wave, the "d-wave," appears as a small positive wave when the light is turned off. The ERG is initiated by the receptor cells in the retina, anid the actual electrical activity of these receptors can be observed in the earliest component of the response (a-wave). The later component of the ERG (bwave) appears to be initiated bv the neural elements in the retina, the bipolar cells, the monophasic, positive c-wave appears to originiate from the pigmnenit epithelium layer and is usually not emphasized in the clinical evaluation of the ERG.9

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AIn important point for the clinical interpretatioin of the ERG is that all the recorded activitv is produced in the outer retinal layers without a contribution from the ganglion cells or the nerve fiber laver. Therefore, optic nerve disease does not produce an ERG abnormality when the usual stroboscopic flash stimulus is used. The ERG can be measured in the light-adapted (photopic) or the dark-adapted (scotopic) state. Because the signal of the rods is weakened by light, the photopic ERG is strongly influenced by the cones. The photopic ERG is of lower amplitude (height of the b-wave) and of shorter latency (time from the stimulus to the peak of the 1-wave) than is the scotopic ERG (Fig 1A). The response and the recovery of cone sensitivity is much faster than that of the rods and allows repetitive stimulation at a rapid frequency (25 Hz or greater). With use of a flicker stimullus, the cone-imediated ERG can be isolated. The scotopic ERG requires at least 10 minutes of dark adaptation. This ERG is strongly influenced by rod activity and has a b-wave with a longer latency and higher amplitude than that of the photopic ERG (Fig iB). Because of the greater sensitivity of the rods, their contribution can be studied with dim stimuli that are too weak to excite cones. Under the appropriate dark-adapted conditions, a light stimulus of high intensity will elicit two or three positive deflections superimposed on the ascending liml) of the b-wave. These deflections are called oscillatory potentials and most probably originate from the inner nuclear laver. They increase in number with increasing light intensity and continued dark adaptation. 10 The fact that rods and cones do not have the same spectral sensitivities can also be utilized clinically to isolate rod and cone responses in the scotopic ERG. With the use of red light, the cones can be excited more strongly than the dark-adapted rods. Similarly, the rod contribution to the scotopic ERG can be obtained almost exclusively by using shortwavelength stimuli, ie, blue light, to which the cones are relatively insensitive. Because of the large area being stimulated by the stroboscopic light and the distribution of rods and cones in the retina, the ERG does not detect small lesions of the retina. Macular scars, while involving mostly cones, cannot be expected to result in a smaller photopic ERG, because of the numerous cones scattered throughout the peripheral retina. Retinitis pigmentosa, which affects the peripheral retina with its higher concentration of rods, leads to a significant change in the ERG even though visual acuity (dependent upon macular function) may not be affected. The ERG, therefore, can be normal in patients with poor vision secondary to macu-

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B FIGURE 1

A: (Top) Light-adapted ERG has a large a-wave with a b-wave of short latency and low amplitude. B: (Bottom) Dark-adapted ERG has no a-wave and a b-wave with a longer

latency and larger amplitude.


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lar disease and abnormal in patients with good vision but peripheral retinal degeneration. Changes in the peripheral retina may be extensive, with loss or marked attenuation of the ERG before clinical changes in the appearance of the retina are present. The ERG is, therefore, a poor gauge of visual acuity but a sensitive test for early changes in the outer retinal layers of the peripheral retina. The use of a patterned stimulus to evoke the ERG has recently been shown to reflect changes in the ganglion cell and nerve fiber layers of the retina.11"2 Abnormalities of these layers following optic nerve atrophy in humans and section of the optic nerves in cats resulted in loss of the ERG elicited by checkerboard pattern stimuli, although the ERG elicited by a stroboscopic flash in such cases is not affected. 13"14 Loss of vision due to other causes, eg, amblyopia, may also lead to changes in the patternevoked ERG, but this has not yet been well established. 13-18 VISUAL EVOKED RESPONSE

The VER is a specific cortical potential measured over the visual cortex. It is related to a light stimulus, which may be either a flash or a specific visual stimulus such as a checkerboard pattern or a spatial frequency grid. It differs from the electroencephalogram (EEG) in that the latter is a record of the continuous, spontaneous, unprovoked activity of the brain, although manipulation of external stimuli can produce changes in its frequency spectra and magnitude. The VER can also generally be evoked at lower light intensities than can the ERG. In 1929 Berger19 studied the electrical activity of the brain using scalp electrodes. His discovery led to the development of electroencephalography as a valuable clinical tool and a useful research technique. Various sensory stimuli modify the EEG, an example being the reduction or ablation of the alpha rhythm when the eyes are opened. This is a "nonspecific" response. In 1937 Cruikshank20 found that when the eyes were illuminated to block the rhythm, a brief but identifiable and repeatable change occurred in the EEG. This change seemed to be related to the type of illumination and thus was a "specific response," the visually evoked response. Other specific types of responses include auditory evoked responses and somatosensory evoked responses. The amplitude of the VER varies between 1 and 20 ,uV, while the EEG contains signals that may attain amplitudes between 20 and 100 ,uV or even larger. Since the size of the VER is so small when compared to the ongoing EEG, little further investigation of this phenomenon could be done until a method could be found to separate it from the EEG. While

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FIGURE 2

Diagram of electrode placement, stimulus and electronic equipment required for recording VER. (From Sokol S: Visually evoked potentials: Theory, techniques and clinical applications. Surv Ophthalmnol 1976; 21:18-44.)

the VER is "time-locked" to the light stimulus and is a constant response to the type of stimulus used, the EEG is random and continuous. By using a computer to analyze the electrical activity occurring just after each stimulation and evaluating a number of such waves by summation or averaging, the random EEG begins to approach a baseline. The VER, which is constant in its waveform in the time studied, will be visualized as separate from the background "noise" of the EEG.21 A computer of average transients has been used by most laboratories to study the VER, since it allows separation of the two waveforms and, by averaging a number of responses, allows magnification of the VER for easier study (Fig 2). Unlike the alpha rhythm, which can be recorded from most regions of the cortex, the evoked response to light is limited mainly to those leads overlying the occipital poles of the brain. Because of the number of flashes required in averaging, it is relatively easy to establish an adequate intensity level for a particular study simply by using an intensity that does not produce significant subject discomfort and yet gives an adequate signal size to allow measures of reliability and separation from the "noise" of the background EEG. The VER (also called cortical evoked potential, evoked occipital potential, photic evoked potential, visual evoked cortical potential, and visual evoked occipitogram) does not have as well-defined a waveform as the ERG. When evoked by stimuli presented at a slow rate, it is a complex polyphasic wave of positive and negative components (Fig 3). The num-


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EVOKED POTENTIAL

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RHYTHMIC AFTER-DISCHARGE

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100 msec FIGURE 3

A: (Top) VER is a polyphasic wave of positive and negative deflections. Note change in time scale at 240 ms. B: (Bottom) Numbering of waveforms according to Gestaut and Regis.23 (From Perry NW, Childers DG: The Human Visual Evoked Response. Springfield, Ill, Charles C Thomas, 1969, pp 7-8.)

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ber of positive and negative deflections of the VER is a function of the experimental conditions and the subject. Successively faster rates of stimulation, narrow band-pass filtering, or discrete retinal stimulation produces VERs of varying shapes that tend to become more like distorted sinusoids. Using light flashes of 4 Hz or less, a definite series of wave forms or components is seen from 50 to 250 ms after the stimulus. These components have been numbered from I to VII by Ciganek22 (Fig 3A) and from I to VI by Gastaut and Regis23 (Fig 3B). The total components have generally been divided into three time segments, with the segment closest to the onset of the stimulus considered primary, the next considered secondary, and the last considered some sort of after-discharge. The primary response appears to be most sensitive to the type of stimulus presented. Increasing the intensity of stimulation produces VERs that are characterized by greater complexity, greater amplitude, and shorter latencies. The waveform of the VER is dependent on both stimulus and patient variables. Presentation of a flash stimulus at a rate of 4 Hz or less will prod(uce a transient VER waveform that can be described according to the amplitude of one of the positive or negative waves, or by the time it takes from the stimulus to the peak of the wave selected (the implicit time of the wave). The amplitude is usually measured from the trough of a negative wave to the peak of a positive wave (Fig 3). In most cases the choice of which waveform to measure has been somewhat arbitrary depending on the type and form of wave produced in the investigator's laboratory.24 As the frequency of the stimulus is increased, a "steady-state" VER develops, which is sinusoidal in shape and directlv proportional in frequency to the frequency of the stimulus. The point at which the VER becomes steady-state with increasing frequency of stimulus varies and is not clearly defined. As a rule, transient VERs are generated at less than 6 Hz and steady-state VERs are measured at 10 Hz or more. In the case of steady-state VERs, the amplitude of the signal is measured as a function of the frequency of stimulation. Regan25 has shown that the greatest relative amplitudes are found in three regions: a low frequency at 10 Hz, a medium frequency around 13 to 22 Hz, and a high frequency from 42 to 60 Hz. The three frequency components are thought to travel through parallel channels in the brain. They have been shown to react differentially to variable stimuli, eg, spectral variation, and to pathologic changes in the central nervous system (CNS), eg, in multiple sclerosis. Spectral variation in the stimulus has been shown to result in a variation in the amplitude of the VER that is directly related to the retinal


391

spectral sensitivity. That is, the peak VER sensitivity is at 570 nm in the light-adapted state.26 While producing fewer light waves in the red spectra, the usual stroboscopic flash stimulus allows maximum stimulation by the most sensitive wavelengths. For this reason, monochromatic light is not generally used to produce VERs. PATTERNED STIMULI

The VER is extremely sensitive to stimuli that contain contours and edges. That is, there is a great variation in the form, amplitude, and implicit times of the VER depending on the type of patterened stillmulus presented. Patterned stimuli are usually produced as a grid of vertical alternating black and white stripes (spatial frequency grid) or as a checkerboard pattern. The size of the stripes or the checks can be varied for a given test. The stripes/checks are varied from black to white or from present to ab)sent either sinusoidally or in sudden increments. The luminance of the stimuluis canl be kept constant or flashed to produce either a steady-state VER or a transienit VER, respectively. Bv changing the size of the stripes/checks, a measure of visual acuity can be made. This has been demonstrated best in cooperative adults, but has also been used in children to estimate the development of vision in infants andl to follow acuity changes during amnblyopia therapy.27,28 Careful attention must be given to the optical quality of the patterned stimulus. A small variation in the clarity of the image can produce a marked change in the form of the VER.24 For this reason, the patient must be fully and correctly fitted with the refractive error and, if the screen is placed at a near distance, eg, 1 m, careful attention mulst be paid to accommodative effort to maintain a clear image. The size of the checks will also affect the VER. Maximum responses are seen with checks that subtend visual angles of between 10 and 20 minutes of arc.29 At some point the large check size begins to behave like a flash stimulus, as fewer checks are presented and the number of contoured edges diminishes. For patients with extremely poor vision, the large checks needed to produce a visual response are really little different from the usual flash stimulus. When small targets are used, the position on tlte retina can lead to variation in the form of the VER.30 If the small-chleck-sized stimulus is not kept on the central 30 of the macula, significant and variable changes in the waveform of the VER occur. The electrical signals recorded from the scalp overlying the occipital lobe reflect the activity of the central 60 to 120 of the visual field. This is due to the projection of the retinal fibers to the occipital cortex. The

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central fibers, originatiing from macular receptor cells, project to the posterior, most exposed surface of the cortex, while those fibers originiatinlg in the peripheral retina reaclh the medial aspect of the occipital cortex deep within the calcarinie fissure.3' Electrodes placed over the occipit are thus physically located over a region that receives input from the central visual field. Changes in this area, eg, reduced visual acuity, macular disease, and amblvopia, miglht be expected to produce a significant change in the VER. Coniverselyr, disorders of the peripheral visual field, even those that produce significant loss of retinal function, eg, retinitis pigmiienitosa, would not be as easily discovered using the VER. In addition to the anatomic locationi of the central fibers in the most posterior portion of the occipital lobe, there is also a significant magnification factor. The fovea takes up a much larger portion of the surface of the occipital cortex than might be expected on the basis of its anatomic area. 32,33 Each 1 mm of tissue in the cortex represents 2 minutes of visual angle if the fibers come from the fovea, but if the fibers are extrafoveal, that same 1 mm of tissue represents 18 minutes of visual angle.34 Another way of representing the foveal magnification is to point out that a distance of 5 ,u on the fovea (about the width of two cones) is magnified to an occipital width of 500 pL with an area that is 10,000 times as great as that on the fovea. It should be evident, then, that when the VER is recorded, central retinal function is selectively tested. The VER, therefore, is a measure of the central retinal elements and their transmission to the occipital cortex through the visual radiations. Any abnormality of macula, optic nerve, or CNS visual system that affects central vision will result in a change in the form and latency of the VER. The use of contoured stimuli, either stripes or checks, in the cooperative patient can enhaince the sensitivity of the visual system. However, the use of contoured rather thani flash stimuli has failed to produce consistent results in very young or retarded children with poor vision, short attention spans, and poor cooperation. NIATERIALS AND METHODS

The same stimuli and recording equipment normally used for adults is used for children, except that ERG electrodes and the test protocol are altered. The ERG is detected by subminiature Ag-AgCl skin electrodes placed below eachi eye on the infeiior orbital ridge (Fig 4). This location was chosen because it yields the greatest amplitude and the waveform is not altered by changes in the direction of gaze.35 Indifferent electrodes for each eye are placed at the temples. The VER is recorded from two


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FIGURE 4

Placement of Ag-AgCl electrodes at infra-orbital ridge to record ERGs.

silver drsc electrodes. The positive electrode is placed on the midline 2 to 3 cm above the inion, and the negative electrode is placed 5 to 6 cm higher (Fig 5). An ear clip is used to ground the patient (Fig 6). During the course of this study, two methods of recording were used. In the first method the electrical signals from each electrode pair were amplified by battery-powered differential amplifiers. The amplifiers had a gain of 1000, a common mode rejection ratio of 120 dB, and a frequency response that was flat (-3 dB) from 0.2 to 350 Hz. The amplified signals then went to a Fabri-Tek 1052 4-channel signal averager. The averaged responses were photographed for subsequent analysis. In the second

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FIGURE 5

Placement of silver disc electrodes on scalp to record VER.

method a programmed LKS (ETAS-E 1000) amplifier was used with a flat frequency response between 0.3 and 500 Hz and an artifact rejection capability. The results were printed out on an X,Y printer. A Grass PS-2 photostimulator provides the stimulus flashes. A filter holder mounted on the photostimulator housing allows colored or neutral density filters to be inserted in front of the stimulator. The photostimulator is hand-held or is mounted on an adjustable arm so that it can be positioned in front of the patient (Fig 7). After the patient's pupils are dilated and the electrodes are attached, photopic responses are recorded. Ordinary room lights provide an illumination level of about 25 lux, which is sufficient to saturate rod responses. Testing is started with a stimulus frequency of 4 Hz. The ERGs from both eyes are recorded simultaneously, using a signal averager display of 200 ms. The signal averager display is then changed to 500 ms and the VER is recorded along with the ERG. If the VER is absent and the ERG is


395

FIGURE 6

Ear clip uised as a

grouind electrode. Note patienit

is

"sedated" by uisinig his bottle.

present, the stimulus frequency is reduced to 2 and finally to 1 Hz. This is done in very young or retarded children because their relatively undeveloped visual svstem does not seem able to respond to a higher stimulus frequency.36,37 If there is a reason to suspect a difference in vision between eyes, monocular VERs are recorded: first one eye and then the other is covered by a thick black cloth. The adeqjuacy of the cover is verified by the absence of an ERG from the covered eve. Usually between 128 and 256 flashes are averaged. In those circumstances where the stimulus frequency is 4 Hz, the displav will include one ERG if 200 ms is included, and two ERG and VER responses if 500 ms is included (Fig 8). In the latter case the similarity of response between the VERs is extremely helpful in its detection. The ERG response is present in the first 120 ms, with the a-wave appearing at about 50 ms after the stimulus. The a- and b-wave are usually easily identified. No attempt is made to exactly quantify these responses, since fairly large individual variations are possible. If scotopic responses are to be recorded, the room lights are turned off and the patient is dark-adapted for 10 minutes. Both cone and rod system

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FIGU'RE 7

Crass PS-2 photostimuitilator with filter holder moutnted oni housinig in front of stimuLlator.

responses can be recorded bv using a red or blue filter, respectively. Scotopic responses are recorded only when thev are required to establish a diagnosis. The VER is extremely variable from patient to patient and has been shown to be dependent on attention. " For this reason, we have only been concerned with its presence or absence. The VER appears about 50 ms after the stimulus and has its largest deflection at about 150 ms. It is best seen in the 500-ms scan. Omitting the dark-adapted portion of the test allows the testing time to be held to a minimum. This is especiallv advantageous because children quickly become restless. The total time required for the examination is approximatelv 40 minutes. PATIENTS

A total of 302 patients were included in this studv (Table I). The patients ranged in age from 12 davs to 20 vears. The mean age at the time of the


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FIGURE 8

Simtitaneous recording of ERGs and VER. Stimtilus fre(luenev 4 Hz with 5(X) ms sweep

speed.

examination was 3.6 years and the median age was 2 years. There were 159 males and 143 females. All patients had been seen by a pediatric ophthalmologist and had had a complete examination, including a cycloplegic refraction and an indirect ophthalmoscopic examination of the fundus. Many of the patients were referred from a state institution for evaluation of visual function or for help with a neurologic diagnosis. Eighty-two (27%) were said to be mentally or developmentally retarded (Table II). Thirty-eight (13%) had been diagnosed as having cerebral palsy and 54 (18%) had seizures or some other form of neurologic dysfunction.

Hydrocephalus, microcephaly, multiple congenital anomaly syndrome, juvenile amaurotic idiocy (Batten disease), Leber's congenital amaurosis, and retinal degeneration associated with systemic disease (eg, LaurenceMoon-Biedi syndrome) were also encountered. Ocular findings at the time of ophthalmologic examination included optic nerve disease, glau-

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TABLE I: PATIENTS INCLUDEI) IN STUDYn = 302)

Age ranige Nleani age (yr) Median age (yr) Males Females

12 davs-2() vr 3.6 2 159 143

retinal disease, and strabismus (Table III). Nvstagmus, colobomas of the nerve and retina, and achromatopsia were also encountered. Children presenting with congenital or traumatic cataracts were routinely evaluated bv 10th ultrasonographic and electrophvsiologic techniques

coma,

prior to

surgery.

The records of all patients were reviewed and the data entered into a computer data base for ease of analysis. Patients were divided into groups according to age, results of ERG and VER testing, and diagnosis. Only qualitative data were entered, since the method of testing did not allow quantitative analysis of the data owing to individual and test condition variability. Statistical analvsis of available quantitative data (eg, age, sex) was done using the data base statistical package. RESULTS

ERGs could be produced using skin electrodes under both light-adapted and dark-adapted conditions (Fig 1A). The light-adapted ERG showed the usual a- and 1)-wave configurations with a latency of the b-wave seen at 25 TABLE II: SYSTEMIC DISEASE IN 3()2 PATIENTS

Mental/developmental retardation Neurologic abnormality Cerebral palsy Hvdrocephalts Microcephaltis Multiple congenital anomalies Batten disease Laurence-Moon-Biedl syndrome Albinism

NO

%

82 .54 38 20 13

27 18 13 7

5 4

2 1

Progressive external

ophthalmoplegia Hysteria

1 1


399

TABLE III: OCULAR DISEASE IN 302 PATIENTS

Cataracts Congenital with PHPV Acquired Optic nerve disease Atrophy

Hypoplasia Coloboma Glaucoma Strabismus Esotropia Exotropia Nystagmus Vitreous hemorrhage Retinal disease Retinitis pigmentosa Retinal degeneration Leber's congenital amaurosis

Achromatopsia Congenital stationary night blindness Central retinal artery occlusion

27 8 9 63 20 4 4

37 18 16 2 5 7 9 3

1 1

ms. With dark adaptation, the amplitude of the b-wave and its latency increased (Fig 1B). Stimulation using a blue filter enhanced the rod response under scotopic conditions. The VER showed the usual polyphasic waves with an implicit time of 50 ms and a peak amplitude at 150 ms. The form of the VER varied considerably from patient to patient depending on the cooperation, level of awareness, whether the eyes were open or closed, and the physical shape of the skull (eg, in patients with hydrocephalus). The presence or absence of the VER was determined by comparison of the two wave forms present in the 500-ms print-out. If there was a waveform that was consistent in shape and timing after each stimulus, the VER was said to be present. If the waveform was inconsistent in its shape or position, it was considered abnormal or absent. In those cases where stimulation at a rate of 4 Hz failed to produce a consistent response, but a stimulation at 2 Hz produced a consistent waveform after each stimulus, the VER was considered to be present if the patient was an infant or was retarded. If the patient was otherwise normal and was 1 year of age or older, the VER was considered to be abnormal. ERG AND VER DEVELOPMENT IN INFANTS

Both ERGs and VERs were present and recordable in infants from the

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FIGURE 9

A: (Left) Patienit SM, age 2 weeks. Stimulus fre(luency 4 Hz. B: (Right) Same patient, stimulujls frequeniey 2 Hz.

age of 12 days. The ERG in the light-adapted state was produced with 4-Hz stimulation and was a compound wave with both a- and b-wave components. In patient SM at 2 weeks of age, the ERG showed a typical waveform (Fig 9A and B) when the stimulus was presented at 2 Hz, but the a-wave was less well defined when the stimulus rate was 4 Hz. By 3 months of age, the size, shape, and latency of the ERG was similar to that

FIGURE 10

ERGs; patient JB, age 3 months. Stimulus frequency 4 Hz.


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FIGURE 11

ERG dark-adapted with oscillatory potentials on risinig b-wave, age 7 months

FIGURE 12

A: (Left) Patienit TI, age 12 days. Stimiulus frequency 4 Hz. B: (Right) Same patient, stimilulus frequency 2 Hz.

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FIGURE 13

VER; patient JB,

age

3 months. Stimulus frequency 4 Hz.

seen in adults (Fig 10). Waveform complexity increases during the first 6 months of life. Oscillatory potentials can be demonstrated in infants by 3 months of age and are prominent in the recording shown of a patient at age 7 months (Fig 11). The VER shows a slower development and is best seen when the stimulus frequency is 1 or 2 Hz. Stimulation at 4 Hz results in a poorly defined and occasionally absent waveform in these younger children. In a patient 12 days old, a polyphasic waveform was seen at both rates of stimulus but was more complex and had a shorter implicit time at 2 Hz (Fig 12A and B). In patient SM at the age of 2 weeks (Fig 9A and B), the TABLE IV: PATIENTS WITH NORMAL ERG AND N'ER (n = 171)

Average age (yr) Median age (yr)

Males Females

3.15 2.00 86 85

Electrophysiology in Children TABLE

403

V: SYSTEMI(C DISEASE IN PATIENTS WVITH NORMAL ERG AND VER

Ps\ychomotor retardlationi Cerehral palsx SeizoLres/Netnrologic (lvs-

39 22

finctioll

33 11

Hydrocephalns Nlicrocephaltns Multiple congenital anomiialxy syndrome Rtl)ella syndrome Albinism

4

Sturge-WVeber Synldrome

1

I

2

1

wave was absent when a 4-Hz stimulus rate was used but appeared well formed with the 2-Hz stimultis. By 3 months of age, the VER was well formed even at 4 Hz in patieint JB (Fig 13). With delayed maturation, however, as in children with significant CNS anomalies, the development of the waveforminay he delayed and require slower rates, even to the age of 1 year.

TABLE

I: O()ClLAR DISEASE IN PATIENTS WITH

NORMAL

ERG

AND) VER

Cataract

Conigeniital Uniilateral (PHPV = 6) Bilateral

Acquiired Traulmatic Svstemic (lisease Optic nierve disease Optic atrophy

Hypoplasia Coloboma Nystagmus

16 9 4 1

24 7 3

10

Strabismuls Esotropia Exotropia

Oculomotor apraxia NMicrophthalmuis

Retrolenital fibroplasia Aniiridia Vitreous hemnorrhage Normal examinilationi/poor visnial responises

26 8 2 4

3 1 2

61

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France PATIENTS WITH NORMAL ERGs AND VERs

In 171 patients ERGs and VERs were normal at the time of examination, even though visual dysfunction was suspected either on the basis of visual inattention or neurologic or ophthalmologic examination (Table IV). The associated systemic diagnoses are shown in Table V. Thirty-nine children had some form of developmental delay, 22 were known to have cerebral palsy, and 11 had hydrocephalus. Twenty-nine patients presented with cataracts, either congenital or acquired (traumatic or associated with systemic disease (Table VI). Six of these had cataracts associated with mnicrophthalmos and persistent hyperplastic primary vitreous (PHPV). As noted previously, patients presenting with dense cataracts preventing evaluation of the posterior pole were all tested with ultrasound and ERG/VER prior to surgery. Twenty-four patients were diagnosed as having optic nerve atrophy at the time of ophthalmologic examination and 7 were found to have hypoplasia of the optic nerve. Ten patients had nystagmus and poor visual responses. No other ocular abnormalities were found, and ERG/VER testing was performed to help rule out primary retinal disease or CNS disease. Other ocular abnormalities included aniridia (1), microphthalmos (4), Peters' anomaly (1), optic nerve coloboma (3), vitreous hemorrhage (2), and retrolental fibroplasia (3). Thirty-four patients had strabismus associated with their visual disturbance. Twenty-six (76%) of these had esotropia and 8 had exotropia. The most common cause of referral, however, was suspicion of CNS abnormality of the visual pathways or visual cortex. Sixty-one patients with this concern were evaluated and found to have normal responses. The usual finding was a child who would not respond to any visual stimulus, including a bright indirect ophthalmoscope, and who had an associated CNS disorder. Frequent seizures, severe developmental delay, and hydrocephalus were the most common associated problems. In those cases where there was no visual response, or where fixation and following were reduced in frequency or time, the children were diagnosed as having a "perceptual blindness." There was a normal ERG/VER to indicate that the visual radiations were intact, with no apparent occipital cortical abnormality. The visual processing of this information appeared to be lacking owing to malfunctioning higher centers. Our opinion was that while the eye and visual pathways were intact, the higher processing of this visual information was not taking place so as to allow awareness of the visual surround. Others have called this "cerebral blindness" but have used this to indicate significant and global CNS damage. 39


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CASE REPORTS CASE 1

TC was seeni at the age of 5 years following cardiac surgery to repair a ventricular septal defect. lDuring the operationi she had experienced a brief hvpoxic spell and sul)se(uentlv had several small, myoclonic seizures. 'We were asked to see her 4 davs postoperatively to evaluate her apparent lack of visual responses. The following findings were noted: Fixation, will not fix or follow on any object, does not respond to a bright light; pupils, equal, round, react to light (PERRL); extraocular movement (EOM), normal; fundi, normal; ERG, normal both eyes (OU); VER, present when either eye stimulated; EEG, diffuse abnormalities present. The clinical impression was perceptual blindness with intact visual pathways following a hypoxic intraoperative episode. Five days postoperatively the patient began to fixate and would follow a small toy. Ten days postoperatively she had continued to improve, with visual acuity 6/9 right eye (OD) and 6/12 left eye (OS). The clinical impression was improving visual attention with overall improvement in mental status. CASE 2

RF was seen at the age of 2 vears following cardiac surgery to correct transposition of the great vessels (Mtustard procedure), which was complicated by cardiac arrest 2 days after surgery. She had been placed on a respirator for 3 weeks, and when she had recovered sufficiently to be evaluated, she was founld to be unresponsive to visual stimuli even though she could verbalize and appeared otherwise normal. Clinical findings included: fixation, does not fixate or follow a light or toy; PERRL; EOM, normal; fundi, normal OU; ERG, normal OU; VER, normal when either eye stimulated; EEG, diffuse abnormalities present. The clinical impression was perceptual blindness secondary to a hypoxic episode during cardiac arrest. Visual pathways were intact. One month later the patient showed full recovery of visual function with normal fixation and following for her age. COMMENT

These two patients had an acute hypoxic episode associated with surgery to correct a cardiac defect. Their initial visual loss was not related to any apparent defect in their central visual pathways as measured by the VER. Immediately after the insult EEG testing in both cases showed diffuse abnormalities over the entire brain. This slowly cleared. Within a few days or weeks the visual function returned to normal without any sign of residual defect. In these cases the VER did not correlate with visual function, since it appeared to be normal in a patient who did not respond to visual stimulation. It might be thought to be prognostic, however, since return of visual responses occurred with improvement of the general CNS condition. We could tell the parents that the visual system did

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not seem to have been damaged and might be expected to be better utilized as the child generally improved. Weinberger et al4' reported three similar cases of acute cortical blindness following cardiac arrest, with visual improvement occurring over a period of several months to several years. VER testing was not done in these patients and might have been helpful in determining the extent of cortical damage. CASE 3

BO was 8 months old when he was first seen for visual evaluation. He had hydrocephalus at birth and had been shunted, but several shunt revisions were required after the original surgery. Following the most recent revision he had been found to have poor visual responses. In addition to hydrocephalus he had other neurologic problems, including seizures and psychomotor delay. The following findings were noted on examination: fixation, does not fixate on objects or respond to light; pupils, (?) responsive to direct light OD, unresponsive OS; ET' = 25 A; versions, normal; ref, + 0.50 + 1.00 x 120 OD, + 1.75 + 0.75 x 45 OS; fundi, discs moderate atrophy OU; ERG, normal OU; VER, present. The clinical impression was optic nerve atrophy with an intact visual pathway. One year later the patient showed normal fixation movements with both eyes, and moderate optic nerve pallor persisted. Six years later, at the age of 8 years, the patient exhibited severe psychomotor retardation and continued to have seizures. Although vision appeared to be normal, some rotary nystagmus was present, which increased on side gaze, and a moderate "A" pattern esotropia had developed. CASE 4

KT was seen at the age of 10( months for evaluation of a left esotropia. She had been followed by an ophthalmologist for several months, and patching of the right eye had been attempted to correct the ocular preference. Pregnancy and delivery were said to have been normal. Clinical findings included: fixation, central, steady, and maintained (C,S,M) OD but not OS; pupils, direct reaction OD, + Marcus Gunn OS; LET = 60 A; ref, +3.75 OD, +2.75 OS; fundi, disc, normal OD, marked hypoplasia OS; ERG, normal; VER, normal response from either eye. The clinical impression was a hypoplastic optic nerve OS with retention of central visual pathways. COMMENT

The presence of normal VERs with the obvious abnormality of the optic nerves in these two patients must imply that the visual pathway to the occipital cortex is still partially intact. The poor vision seen in case 4 would indicate that either the intact fibers were not enough to provide good vision or an amblyopia had developed secondary to her strabismus,


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TABLE VII: PATIENTS WITH NORMAL ERG; AND = 91) ABNORMAL N'ER

Average age (vr)

Mediani age M4ales Females

(yr)

3.8 2.0 52 39

which might be treatable by occlusion. The fact that there had been little improvement with occlusion for 3 months would tend to deny this conclusion. The ability to predict the visual result of optic atrophy on the clinical appearance of the disc assumes that there is uniform loss of axons that include all areas of the retina. The presence of useful vision in many such patients is not an uncommon finding, however. The normal VER in case 3 would seem to indicate that some of the central fibers were still intact and might have been predictive of some useful vision after the general CNS problems had improved. PATIENTS WITH NORMAL ERGs AND ABNORMAL VERs

Ninety-one patients, mean age 3.8 years, were found to have normal ERGs but abnormal VERs (Tables VII and VIII). Although the male/female ratio of 52:39 was slightly higher than in the other groups, this did not appear to be related to any particular disease entity. Thirty-four patients had developmental delays, 16, had cerebral palsy, and another 16 had a significant CNS defect, usually seizures. Eight patients had hydrocephalus. Thirty-five patients had been found to have poor visual responses and optic atrophy, and 13 had significant optic nerve hypoplasia

TABLE XIII: ASSOCIATED SYSTEMIC DISEASE IN PATIENTS WVITH NORMAL ERG AND ABNORMAL \ER

Psychomotor retardation Cerebral palsy Neurologic dysfunction Hydrocephalus

Microcephalus Rubella syndrome Congenital toxoplasmosis Sturge-Weber syndrome

34 16 16 8 5 1 1 1

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TABLE IX: OCULAR DISEASE IN PATIENTS WITH NORMAL ERG AND ABNORMAL XrER

Optic nerve

Atrophy Hypoplasia Coloboma Cataract Nystagmus

35 13 1 2 6

Strabismus Esotropia Exotropia Cortical blindness (normal eye)

10 10 39

(Table IX). Thirty-nine patients with absent/abnormal VERs were diagnosed as having cortical blindness. They had significant visual loss, no ocular pathologic findings or insufficient findings to explain the severe visual loss, and a history of neurologic insult, either acute or chronic.4'l The presence of an abnormal VER did not necessarily imply that the visual pathway damage was permanent or that the patient had no useful vision.

Two patients with cataracts had abnormal VERs and were subsequently found to have other CNS abnormalities, which suggested that cataract removal would not benefit vision. Ten patients had esotropia and 10 had exotropia. CASE 5

JT was first examined at the age of 7 months for evaluation of visual function. He had been born prematurely (birth weight 2 lb 9 oz) and had never shown good visual following movements. He had been evaluated by an ophthalmologist, who thought the optic nerves were slightly atrophic. The child exhibited severe psychomotor retardation and was placed in a state institution. Clinical findings on examination were as follows: fixation, no response to light, no apparent fixation or following movements; PERRL; EOM, no nystagmus, full range of motion with head movement; ref, + 3.00 OU; fundi, discs mild pallor OU; ERG, normal OU; VER, no response at 4, 2, or 1 Hz (Fig 14). The clinical impression was visual loss secondary to optic atrophy. Four years later the patient responded to a bright light but showed no other sign of fixation. The optic nerves showed 2 + atrophy. COMMENT

The optic atrophy in this patient did not seem severe enough to explain the loss of vision, but was found to be disrupting the central visual pathways to such an extent that it led to loss of the VER. With some


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CASE 5: ERGs normal and VER absent.

maturation, there was an apparent appreciation of visual stimuli but still no useful central vision. CASE 6

AS was examined at the age of 13 months for evaluation of a left exotropia (LXT) and possible hypoplasia of the optic nerve. The exotropia was noted by the second month of life and poor vision was suspected. An ophthalmologist confirmed the poor vision OS and questioned the appearance of the optic nerve. The following findings were noted: fixation, CSM OD, and NC, S, NM OS; pupils, + Marcus Gunn OS; LXT = 20 A; ref, + 0.75 OU; fundi, discs normal OD, moderate hypoplasia OS (Fig 15); ERG, normal OU; VER, normal when OS occluded, absent when OD occluded. The clinical impression was hypoplasia of the optic nerve OS with poor visual prognosis. CASE

7

DP, an 11-year-old girl, had a history of severe visual impairment since birth. She stated that she had never had any vision in the OS but that vision had improved in the OD over the past several years. She was said to have been born 1 month prematurely but had a birth weight of 7 lb 10 oz. She was mildly retarded and in the fourth grade. There was a negative family history of eye disease.

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FIGURE 15 CASE 6: Hypoplasia of optic nerve OS. Arrows show disc with halo of pigment epithelium.

Clinical findings included: vision, CF at 3 ft OD, NLP OS; pupils, reacts well OD, no reaction to light OS; LXT, 150; searching nystagmus OU; ref, -4.00 OU; fundi, discs marked hypoplasia OU, pallor 2+ OD, 3+ OS; ERG, normal OU; VER, small response OU, no response OD or OS alone. The clinical impression was hypoplasia of the optic nerves OU and poor VER with some vision OD. COMMENT

Cases 6 and 7 presented with poor vision and hypoplasia of the optic nerves. The absence of a VER would tend to imply that the central visual fibers are affected. However, not all patients with hypoplasia on clinical examination have an abnormal VER (case 4). Case 6 has some light perception although her vision was too poor to test accurately. The absence of a VER may indicate only that the intact visual fibers are buried too deep in the calcarine fissure to be detected with scalp electrodes. CASE 8

RK was evaluated at 3 years of age for visual function. She was apparently normal at birth, but a viral encephalitis developed at 1 month of age. Severe brain damage resulted and she had had frequent seizures since that time. At the age of 5


411

months she was said to be able to fixate and track with her eyes "on occasion." Horizontal and rotary nystagmus were noted at the age of 11 months, and on subsequent neurologic evaluations no sign of visual response was reported. The following findings were noted: fixation, no response OU; pupils, normal; ref, + 1.00 OU; fundi, discs 2 + atrophy OU; ERG present OU; VER, absent at 4 and 2 Hz. The clinical impression was optic atrophy and probable cortical atrophy following viral encephalitis. CASE 9

BV was first seen at the age of 7 months for visual assessment. She had been previously hospitalized at the age of 9 weeks with a diagnosis of infantile spasms, cortical atrophy, and psychomotor retardation. The child's mother thought she was blind. Findings on examination were as follows: fixation, no response to bright lights or objects OU; EOM, eyes held in left conjugate gaze with some slow, horizontal nystagmus to the left; EX and EX' = 0; ref, + 1.75 +0.75 x 75 OD, + 1.50 + 1.25 x 115 OS; fundi, normal OU; ERG, normal OU; VER, absent OU. Cortical blindness was the clinical impression. One year later the patient returned with obvious visual responses: fixation, not CSM OD, CSM OS(!); PERRLA; EOM = RET = 150 by Hirschberg's method; ref, + 4.00 OD, + 2.00 OS; fundi, normal; ERG, normal OU; VER, present OU. When the patient was 3 years old, her mother reported that she would not look to the right voluntarily. A right homonymous field defect was found. A VER was repeated with the electrodes placed on either side of the midline. There appeared to be a decrease in the response on the left side. CASE 10

AK was first seen at the age of 6 weeks for evaluation for possible glaucoma. He had been born 6 weeks prematurely with a birth weight of 5 lb 1 oz. He was found to have Sturge-Weber syndrome with a capillary hemangioma involving the left side of his face. At the time of initial examination, there was no sign of glaucoma and the fixation reflex was said to be normal. The optic nerves were normal OU. Tonic/clonic seizures developed after viral encephalitis and the patient was seen again at the age of 6 months. Visual responses had apparently been absent since his encephalitis. Clinical findings included: fixation, NC, S, NM OU; pupils, normal; EOM, normal; ref, +2.50 OU; fundi, (??)pallor of the optic nerves OU; ERG, normal OU; VER, absent to 4 or 2 Hz. The clinical impression was cortical blindness following viral encephalitis. Four months later the patient appeared to show some ability to follow a light. One year later he showed normal fixation and attention to a toy. The ERG and VER were repeated. A small, but definitely present, VER was found. At age 3 years, he has normal fixation OD with some preference for OD and minimal signs of optic nerve pallor.

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COMMENT

In these three patients an absent visual response clinically was confirmed by the absence of a normal VER. With time, fixation responses appeared in cases 9 and 10. When the VER was repeated, a normal or near-normal response was found. Previous studies have shown that the recovery from hypoxic episodes or from meningitis can, over time, restore normal or near-normal visual functioning with the appearance of a VER where one had previously been absent.42'43 The prognostic value of VER, then, is not definitive if we wish to use it to help determine the future course for our patients. Certainly not all patients recover from their cortical insult, and the very fact that there has been enough damage to lose the VER may be of value in our understanding of the lesion present. In the previous group of patients, with both ERG and VER normal but with poor visual responses following an acute insult, we may be able to give a better prognosis for return of visual function. The last case to be presented in this group shows evidence of good visual function but has radiographic and electrophysiologic evidence of significant abnormalities of his visual system. CASE 11

MS was first seen at the age of 7 years. He had had meningitis at the age of 15 months with subsequent loss of vision. Some vision slowly returned and he was doing well in first grade. His motor development was slow, but he was intellectually normal for his age. Clinical findings were: vision, 6/60 at 3 ft OD, 6/60 at 10 ft OS; PERRLA; RET' = 6 to 8 A; ref, +2.00 + 1.00 x 60 OD, + 2.00 + 1.00 x 120 OS; fields, normal to confrontation; fundi, normal OU; ERG, normal OU; VER, absent OU(!). A CAT scan showed large areas of cerebral infarction in the occipital regions bilaterally (Fig 16). COMMENT

The presence of visual acuity, although poor, with absent VER and radiographic evidence of extensive occipital lobe injury points out the problem of trying to equate visual function to the VER. The possibility of extrastriate visual centers being brought into play in these young patients may be the answer to the what allows their vision to develop. Spear and associates44 described such changes in animals after ablation of the visual cortex. Ronen and co-workers45 recently reported visual recovery in a series of six cases with loss of vision in the perinatal period or shortly after birth. Barnet and associates46 followed six patients with cortical blindness that had its onset between the ages of 15 months and 9 years. Three patients recovered normal visual acuity, and three showed some recovery


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FIGURE 16

CASE 11: Comptiterized tomographic scan showing marked abnormality of occipital lobes.

but continued to have visual loss. Duchowny and co-workers42 have tried to correlate changes in the latency of the VER with recovery of visual function in children. They found that the VER patterns only correlated with the visual and neurologic status at the time of recording and could not be used for prognostic aid. PATIENTS WITH ABNORMAL ERGs AND NORMAL VERs

Seventeen patients had abnormal ERGs but maintained normal VER responses, indicating poor peripheral retinal function but an intact and functioning visual pathway (Table X). The average age of these patients at the time of testing was 5.5 years with a median age of 6 years. This group was found to be significantly older than the other groups of patients (P < 0.01 using the unpaired t-test). Four patients had late onset of CNS degeneration, seizures, and poor vision and were diagnosed as having juvenile amaurotic idiocy (Batten-Mayou disease) (Table XI). Four pa-

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TABLE X: PATIENTS WITH ABNORMAL ERG AND NORMAL XER (n = 17)

Mean age (yr) Median age (yr) Males Females

5.47 6.00 9 8

tients had retinitis pigmentosa, either autosomal dominant or recessive. Two patients had congenital achromatopsia and one had congenital stationary night blindness. Only one patient in this group had strabismus, an esotropia. CASE 12 was examined in the pediatric eye clinic at the age of 8/2 years. She had poor night vision and a history of slow development. She had been followed by another ophthalmologist since the age of 4 years. Pediatric evaluation had suggested the diagnosis of Laurence-Moon-Biedl syndrome. Findings noted on examination were as follows: vision, 6/18 OD with 14.00 + 4.00 x 97, 6/18 OS, -13.50 +3.00 x 80 OD; pupils, sluggish reaction OU; X' = 12 A; stereopsis = 400"; color vision, 15/15 (PIP); fundi, discs pale and waxy OU, vessels attenuated, retina shows loss of nerve fiber layer without retinal pigmentary changes; ERG, markedly reduced OU (Fig 17); VER, normal. The clinical impression was atypical retinitis pigmentosa consistent with a diagnosis of Laurence-Moon-Biedl syndrome.

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COMMENT

The diagnosis of atypical retinitis pigmentosa in conjunction with slow TABLE XI: DISEASE IN PATIENTS WVITH ABNORMAL ERG AND NORNIAL N'ER

Systemic Mental retardation Batten disease Seizures

Laurence-Moon-Biedl syndrome Renal disease Ocular Retinitis pigmentosa

Retinal degeneration Achromatopsia Congenital stationary night blindness Strabismus (esotropia)

4 4 3

2 1 4 6 2

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CASE 12: Small ERGs with normnal VER in case of Laurence-Moon-Biedl syndrome.

development, obesity, and hypogonadism confirmed the suspicion of Laurence-Moon-Biedl syndrome.47 The retinal findings were not striking and would have easily been overlooked in this uncooperative child. In this case the ERG confirmed the diagnosis. CASE 13

BR was 10 years old when first admitted to the hospital. She had apparently been well until 4 years of age, when her teacher noticed some mild visual defects. By 6 years of age she was having severe eye/hand coordination problems as well as difficulty with her reading. An ophthalmologist found her visual acuity to be 20/50 OU and suggested glasses to correct an astigmatism. By age 8 years her behavior was becoming disruptive and there was definite regression of her abilities. She had a grand mal seizure at age 10 and was started on diphenylhydantoin (Dilantin). Her vision had become decidedly worse and she was now walking into walls. She was referred to the pediatric eye clinic for visual evaluation.

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The following findings were noted: vision, not CSM OD, not CSM OS; duetions and versions, full; EX and EX' = 0; PERRL; ref, +0.50 OU; fundi, discs pale and waxy, attenuation of retinal arteries, abnormal tapetoretinal reflex; ERG, light-adapted no response OU; VER, response present, The clinical impression was retinal degeneration consistent with the diagnosis ofjuvenile amaurotic idiocy (Batten disease). CASE 14

TK was admitted to the hospital at 6 years of age with the chief complaint of decreased vision. Decreased vision was first suspected at 4 years of age and was documenited at a prekindergarten examination at age 5 years. His family felt that his intellectual developmnenit was a little slow, but attributed this to his poor vision. He had no history of clumsiness or of seizures. His older sister had been diagnosed as having Batten disease at the age of 5 years. Physical examination including neurologic examination was thought to be relatively normal with the exception of slowed development. Evaluation yielded the following findings: vision, OD CF 12 ft, OS CF 4 ft; ductions and versions, full; PERRLA; EX and EX' = 0; fundi, discs 2 + pale OU, vessels slight attenuation, macula abnormal and peppery pigmentation OU; ERG, light-adapted no response OU, dark-adapted no response OU; VER, normal response from either eye, light- or dark-adapted. The clinical impression was retinal degeneration consistent with the diagnosis of Batten disease. COMMENT

The juvenile form of familial amaurosis is characterized by visual loss noted between 4 and 7 years of age, with a more gradual motor and intellectual decline. A late infantile form presents with seizures followed by relatively rapid intellectual, visual, and motor deterioration. Originally termed "Batten-Vogt syndrome," it is now called "Batten disease" or neuronal ceroid lipofuscinosis juvenile type.48 The electroretinogram is characteristically abnormal early in the course of the disease, even when few signs of retinal abnormality are present. Harden and co-workers49 suggested that the VER may differentiate the late infantile and juvenile forms. In the juvenile form the VER and vision decline at the same rate. In the late infantile form an abnormally large configuration is present even if the ERG abnormality is absent.5(t The early loss of vision and of the ERG with persistent VER would seem to indicate that both these cases were of the juvenile type. CASE 15

This child was first examined at the age of 10 weeks because of "chaotic" ocular movements thought to be like those seen in opsoclonus. She weighed 8 lb 1 oz at birth. Pregnancy and delivery had been normal. The abnormal eye movements


417

were not noted until about 6 weeks of age and appeared to be worsening. The family history was negative for eye disease. Clinical findings included: vision, did not fixate or follow a light OU; pupils, poor response to light OU; EOM, continuous, conjugate, rapid, and large amplitude movements present, both horizontal and vertical; ref, -0.25 + 1.75 x 180 OU; fundi, disc, vessels, and macula normal OU; ERG, light-adapted no response OU, dark-adapted small response with orange, white, or blue light stimulation; VER, present under both light- and dark-adapted conditions. Congenital achromatopsia was the clinical impression. This patienit has been followed for 11 years. After significant photophobia developed, she was given very dark glasses and eventually fitted with dark contact lenses. With this protection she venitured outside but otherwise refused even to have the shades open in the home. The eye movemiient problem settled into a horizontal, pendular nvstagmnus. Visioni at age 11 was 15/400 OD and 10/200 OS. The fundi still showed little, if any, abnormalitv. Repeat ERG/VER testing at ages 4 and 10 years, respectively, continued to show a normnal VER with an abnormal ERG when light-adapted and markedly reduced, although present, ERG when dark-adapted. COMMENT

Congenital achromatopsia is characterized by poor vision (< 20/200), nystagimus, photophobia, pupils that react poorly or paradoxically, and total absence of color vision."5 The fundus examination is usually normal or shows dystrophic macular changes. The disease is inherited as an autosomal recessive disorder. In older children the diagnosis can be established without ERG testing by proving the presence of total color blindness, a normal peripheral visual field, and poor vision in the 20/200 range. In young children, such as the one noted here, the ERG is mandatory to establish the diagnosis. CASE 16

This 11-year-old boy was initially examined bv an ophthalmologist at 4 years of age because of poor night visioIn. The parents noted that he would not go out on summer evenings with his older siblings once it began to get dark. He would turn on all the lights in the house at night and was clumisv if forced to enter a room with poor illumination. He was told he was hyperopic, and glasses were prescribed. A second ophthalmologist was consulted and the glasses were taken away. One year ago he was examined by a third ophthalmologist who reordered glasses. The boy's mother stated that his visual field appeared to be normal during the day but was extremely restricted at night. There was no family history of night blindness and no associated systemic problems other than moderate hyperactivity, for which he was b)eing treated with me,thylphenidate hydrochloride (Ritalin). On examination the following findings were noted: vision, 20/25 OD, 20/20 OS; ref, +4.25 +1.25 x 130 OD, +3.75 +1.50 x 55 OS; PERRLA; ductions and

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versions, full; EX and EX' = 0; stereopsis, 50"; fundi, discs mild pallor, vessels markedly attenuated, retina abnormal reflex from internal limiting membrane; visual fields, constricted to 300; ERG, responses markedly subnormal when lightadapted, absent when dark-adapted; VER, normal responses when both light- and dark-adapted. The clinical impression was retinitis pigmentosa with field loss. One year later the field loss was constricted to less than 100 on central field OU. COMMENT

Retinitis pigmentosa is the most common blinding disease known to be transmitted by a single gene.52 It is unpreventable and untreatable. It is characterized by progressive loss of night vision and of peripheral visual field. Changes in the fundus include a waxy-pale disc, attenuated retinal blood vessels, and scattered clumps of pigment, especially in the midperiphery, that resemble bone corpuscles. The disease can be transmitted by the autosomal dominant, autosomal recessive, or sex-linked mode. In the recessive forms the progression of the disease is faster than in the dominant form. Blindness may occur quite early in the recessive forms but is often not present in the dominant form until the third decade. This boy had had significant complaints of night blindness for 7 years before the ERG testing had confirmed this diagnosis. While nothing could have been done to prevent the progression of the disease, the child and his parents would at least have been prepared for and knowledgeable about the boy's condition had the diagnosis been made earlier. Although heredity was not a factor in this family, if this condition had been inherited in either an autosomal dominant or recessive mode, the opportunity for early genetic counseling would have been possible. The importance of electrophysiologic testing in the young child is underscored in these cases. The use of skin electrodes to detect ERGs allows for earlier detection of abnormalities and often may define the diagnosis that could not have been discovered until much later (eg, cases 14, 15, and 16). PATIENTS WITH ABNORMAL ERGs AND ABNORMAL VERs

Twenty-three patients had abnormal ERGs and abnormal VERs. Average age at presentation was 4.4 years (Table XII). Five patients had a developmental delay, which compounded the problem of visual response (Table XIII). The most common diagnosis in this group of patients was Leber's congenital amaurosis in nine patients (37%), which was based on the absence of any ERG in infancy with no visual responses, no ocular abnormalities, and, in some cases, a positive family history of blindness in


419

TABLE XII: PATIENTS WITH ABNORMAL ERG AND V'ER (n = 23)

Average age (yr) Median age (yr)

Males Females

4.4 2.0 12 11

the same sibship. Two patients had microphthalmos, colobomas of the optic nerve and retina, and no apparent visual responses. Traumatic retinal detachments were present in two patients with severe mental retardation and self-abusive behavior. One patient had had a central retinal artery occlusion and optic atrophy, one patient had progressive external ophthalmoplegia with significant visual loss, and one patient had severe achromatopsia. Two patients had cataracts and small corneas. The absence of an ERG and VER was confirmed by ultrasound testing, which revealed a retinal detachment in each case. One was unilateral and thought to represent posterior persistent hypoplastic primary vitreous; the other was bilateral and thought to represent congenital disinsertion of the retina. No strabismus was associated with the eye disease in this group of patients. CASE 17

JL was 7 months old when first seen in the pediatric eye clinic. Her mother felt that she was not following objects well at the age of 3 months and first noted nystagmus at age 6 months. Both a pediatrician and an ophthalmologist had examined her at that time and thought that she could see. The pregnancy had been complicated by hyperemesis for the first 5 months, but there had been no other problems. Birth weight was 7 lb 14 oz. The family history was positive for esotropia in a paternal cousin but negative for any blinding diseases. The parents' marriage was consanguineous at the level of second cousins once removed. TABLE XIII: DISEASE IN PATIENTS WITH ABNORMAL ERG AND VER

Systemic Mental retardation Seizures Rubella syndrome Ocular Leber's congenital amaurosis Microphthalmos Cataract Retinal detachment Retrolental fibroplasia

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CASE 17: ERG aind VER absent in patient with Leber's congenital amaurosis.

Clinical findings were as follows: vision, not C, S, or M OU; pupils, slow random constriction not related to light stimulus; EOM, constant, random movements with occasional jerky, nystagmoid movements; ref, + 7.00 OD, + 6.50 OS; fundi, disc normal color and size, vessels normal, macular reflex normal; ERG, absent OU; VER, absent (Fig 18). The clinical impression was Leber's congenital amaurosis.

When the patient was 6 years old, the parents reported some responses to light, but examination at that time failed to reveal any light perception. At the age of 8 years, she continues to have searching nystagmus and unresponsive pupils. The optic nerves continue to appear of normal color, but the retinal vessels are slightly attenuated and the macula has some pigment clumping now visible. COMMENT

Congenital amaurosis of Leber is a recessively inherited condition that has few signs of ocular disease other than failure to develop a normal


421

visual response in early life.;3 Parents who have had no other children with whom to compare their newborn's visual behavior often are not aware of the problem until quite late. Pediatricians and ophthalmologists may not take note of the lack of following fixation in the first few months of life, especially when there are no apparent ocular abnormalities other than sluggish pupillary responses with a normal-appearing ocular fundus. Motor development of the child may be normal in spite of the visual deficit. Abnormal ocular movements, lack of visual response, and pupillary abnormalities should prompt electrophysiologic testing. The complete absence of ERG and VER would appear to be diagnostic of this condition, since it was not found in any other patients in this study with an otherwise normal ophthalmologic examination. CASE 18

A 3-month-old boy was brought to the eve clinic because of a small left eye, intermittent crusting of the eye (which was being treated with sulfacetamide drops), and a "grey appearance of the left eye." The pregnancy and delivery had been normal. There was no family history of eye disease. Findings on evaluation included: fixation, CSM OD, not CSM OS; pupils, normal OD, small and not reactive OS; external examination, cornea 10 mm OD and 8 to 9 mm OS, anterior chamber shallow OS, lens cataract OS; fundi, normal OD, unable to see due to cataract OS; ERG, normal OD, absent OS; VER, normal OD, absent OS. The clinical impression was PHPV with posterior (retinal) involvement. Ultrasonography confirmed the presence of a total retinal detachment OS. Surgery for removal of the lens was carried out to prevent complications of angle closure, but the parents were informed that the visual prognosis was poor. At age 5 years, the patient has 20/25 vision OD but no light perception OS. CASE 19

JH was 15 years old when first exainined because of irritation of the left eye. She was severely retarded and a resident of a state institution. In addition to her mental retardation, she had seizures and a left hemiparesis. One week prior to her visit, staff members noted a "hazy membrane" in the left eye. She was known to have been involved in a fight on the ward 1 week earlier and had possibly been struck in the left eye. Clinical findings were as follows: fixation, CSM OD, not CS or M OS; PERRLA; LXT = 300 by Hirschberg's method; external examination, conjunctiva 1 + injected OS, cornea clear OU, iris posterior synechiae OS; lens, clear OD, total cataract OS. The clinical impression was traumatic cataract with iritis OS. The iritis resolved with therapy over the next month, and cataract surgery was considered. Examination revealed that ERG was normal OD and absent OS and

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VER was absent when the right eye was covered. Ultrasound examination showed questionable total detachment of the retina. The examination was considered "difficult." The clinical impression was traumatic cataract with total retinal detachment. Surgery was deferred. COMMENT

The presence of a cataract in early childhood is an indication for early surgery if visual deprivation amblyopia is to be avoided. Many surgeons now believe that surgery for congenital, unilateral cataracts must be done before the age of 3 months if any useful vision is to be obtained.54 The use of ERG/VER testing can assure the integrity of the visual system from retina to cortex and avoid unnecessary surgery where the visual system is shown to be alnormal. The presence of retinal detachment in conjunction with an acquired cataract in a mentally retarded child should always be suspected, especially if there is evidence of trauma, such as in case 19. Ultrasonography is often difficult in these older, uncooperative children and may not be diagnostic when used alone. CASE 20

DA was first examined by an ophthalmologist at age 15 months because of poor visual responses. He weighed 6 lb 15 oz at birth and was the product of a normal pregnancy and delivery. He had been well until 4 weeks of age, when projectile vomiting developed. The diagnosis was pyloric stenosis, and he was admitted to a local hospital. At that time he weighed 4 11) 8 oz and appeared dehydrated and obtunded. His temperature was not recordable with a thermometer that recorded only above 96 'F. Following surgery, he had several episodes of apnea and blood glucose measurement was as low as 14 mg/dl. Since that time, he did not respond to visual stimuli. At examination, the following were noted: fixation, not CS or M OU, no reaction to a bright light; pupils, equal reactions; EOM, unable to elevate above the midline; fundi, discs 4 + atrophy OU, vessels normal OU, retina peripapillary atrophy OU; ERG, light-adapted and dark-adapted, small response consisting entirely of an a-wave; VER, no response. The clinical impression was bilateral central retinal artery occlusion and optic atrophy. COMMENT

The loss of the inner layers of the retina following central retinal artery occlusion selectively reduces the b-wave portion of the ERG, since the receptor cells of the retina are spared. This produces an ERG that consists only of an a-wave in either the light- or dark-adapted state.55 The cause of this child's ocular problem appear to have been the spell of apnea, the hypoglycemia, or the significant hypothermia complicating his pyloric


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stenosis. The presence of severe optic nerve atrophy was sufficient to explain the poor visual responses, but the ERG explained that the cause of the atrophy was central retinal artery occlusion rather than CNS defect. DISCUSSION

The use of skin electrodes to record ERG was first reported by Motokawa and Mita in 1942.56 Tepas and Armington'7 used a signal averager to enhance the small signal and separate it from any spontaneous artifacts. They suggested the use of skin electrodes in children to overcome the problem with contact lens electrodes and the use of sedation of general anesthesia. Ogden and Van Dyk,58 in 1974, reported on the use of a platinum filament placed beneath the upper lid along the upper fornix to record ERGs in infants and young children. They used chloral hydrate as a sedative and topical ocular anesthesia. The placement of the filament required that the child keep the eyelids closed to avoid blink artifacts. Harden and Pampiglione,9 in 1970, were the first to report on the simultaneous recording of ERGs and VERs using skin electrodes for the ERG. They placed a single electrode on the bridge of the nose to record the ERG from both eyes at once. They felt that eye movements would be less likely to affect the ERG, since the electrical charges would be opposite from each eye and would be expected to cancel each other. Monocular ERGs were obtained by occluding one eye while using the single electrode. In 1974 Harden60 compared the ERGs produced by this method with those of a contact lens. She found that the ERG had a normal configuration but had an amplitude that was about one tenth that of the amplitude seen when using a contact lens. Other authors61'62 have found the amplitude to vary between one tenth and one half of that found with contact lens electrodes. In 1977 Jones and France63 reported on the advantage of recording from electrodes placed on the inferior orbital ridges. They found that this provided a signal with greater amplitude and allowed the ERG to be recorded from each eye separately. MarmorCA found that corneal electrodes can be used in children without the need for sedation. Thirty patients between the ages of 5 months and 6 years were examined using his technique. Only one patient required reexamination owing to lack of cooperation on the first visit. Single flashes were used to produce the ERG, and artifacts induced at the time of the flash could be excluded. No ocular injuries were encountered, but eye movement artifacts were apparently common. While he did not require use of an averager to produce identifiable waveforms, Marmor

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did suggest the use of a storage oscilloscope to allow rejection of artifactitious waves. Use of skin electrodes allows many children to sleep during examination. Harden"0 noted that the amplitude of the ERG was reduced when the lids were closed and cautioned tha lid position should be considered when assessing the results of testing. Uchida and co-workers65 tested 15 adults with both corneal electrodes and skin electrodes. They found that the difference between the opened-eye state and the closed-eye state was statistically insignificant if sufficient light energy was used. A light source with 20 J or greater energy was sufficient to produce similar waveforms in the opened- and closed-eye states. Our studies are in agreement with these findings. While the ERG recorded from skin electrodes has a smaller amplitude than that obtained from a contact lens electrode, the waveform is not significantly changed and can be isolated from artifacts by the use of a signal averager. This method, however, prevents accurate quantitative measurement of amplitudes and latency because of significant variation in these numbers from that seen with contact lens electrodes. When small changes in either of these parameters is anticipated, the use of a contact lens is probably indicated. Fortunately, such small changes are not the rule in most of the retinal conditions encountered in children with poor visual function. ERG IN INFANTS

The development of the ERG in newborns was at first thought to be delayed. Zetterstrom6-68 reported the absence of the ERG during the first few days of life. She found a small b-wave developing during the first year but believed that there was no a-wave present at this age. She suggested that this was due to a lack of functioning cones in the macula and that this was consistent with the belief that central vision did not develop until later during the first year of life. She believed that children born prematurely had a greater lag in development consistent with their delayed maturation. Winkelman and Horsten69,"0 were able to demonstrate both a- and b-wave activity in newborns and premture infants using contact lens electrodes. By allowing sufficient dark adaptation and using a bright-light stimulus, they found the potentials to be smaller than in adults, but the usual waveform was present. They were among the first to point out the importance of ERG testing in children to identify the presence of Leber's congenital amaurosis. Using contact lens electrodes, Shipley and Anton"1 examined ten healthy infants on the first day of life. They remarked on the


425

difficulty in obtaining records free of artifact, because of eye movement. They reported finding waveforms that almost exactly resembled those of the adult and were unable to relate the maturity of the infant to any particular ERG waveform. Using general anesthesia and contact lens electrodes, Francois and de Rouck'2 found that ERG to be characterized by a reduced amplitude of both a- and b-waves. With increasing stimulus intensity, they found little difference between the adult's waveform and the child's waveform. If the amplitude of the a-wave was compared with the b-wave, under different stimulus conditions, some children showed a normal (adult) type of evolution, some showed a predominantly photopic type, and some had only a low-intensity photopic predominance. Flicker stimulation appeared similar to that seen in adults. Barnet and colleagues73 were able to demonstrate ERG responses in infants 6 hours to 5 days old by using contact lens electrodes and a computer of average transients. They used varying wavelengths of light and found that the resopnse of the infant retina to the differing wavelengths was exactly that of the adult, indicating functional photopic vision in this age-group. B-wave function was also present, and they suggested that both photopic and scotopic systems develop together rather than separately, as had been previously thought. Algvere and Zetterstrom,74 also using contact lens electrodes, were later able to demonstrate the development of oscillatory potentials in a series of infants varying in age from 10 to 96 hours. Ten of 15 infants showed oscillatory potentials in the rising b-wave, which was interpreted as being due to a raised threshold of stimulation in the retina. Our patients showed a relatively normal waveform at the age of 12 days with the usual form of stimulation (Fig 12). There was some indication that slower stimulation at 2 Hz produced a better-defined ERG than did 4 Hz in some patients, but this was not a consistent finding. Oscillatory potentials were present in some tracings by the age of 3 months, but these may only represent a difference in the opened-eye/closed-eye state of these older children. In the opened-eye state, the greater intensity of light stimulus would be expected to produce these potentials. VER IN INFANTS

VER development in children has been studied with the use of either a flash or a patterned stimulus. The latter has been extensively used to study the development of visual acuity and to follow patients with amblyopia. Ellingson75'7" found the waveforms to be simpler and to have longer

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implicit times than those of adults. Larger amplitudes were also noted, but all these differences rapidly changed so that by the age of 2 to 3 months, the adult and infant flash VERs were similar. Lodge and associates77 found the VER of a 1-day-old infant to be extremely similar in appearance, if not in amplitude, to that of the adult. They suggested that some of the differences previously reported were due to the fact that the infants were usually asleep at the time of testing. They believed that deep stages of sleep led to an increase in the implicit times that had been reported. The use of contoured stimuli (either vertical gratings or checkerboards) to study visual acuity development in infants would appear to indicate rapid maturation of the visual radiations. VERs to 20/20-sized stimuli were reported by the age of 6 months.7879 However, we still do not know if the infant does, in fact, have the ability to see (ie, perceive) such targets at this age. These studies would seem to confirm our opinion that VERs can be recorded from normal children as early as the first day of life and can be expected to be a useful test of the integrity of the visual system at even this early age. The question of a possible influence of mental retardation on the VER (and on the ERG) has been raised by the work of Nawratzki and associates,36 Shapira and colleagues, 80 and Merin and coauthors."8 Nawratzki's case appears to be similar to our case 10, with loss of visual responses following a viral meningitis. Visual responses improved with time. The continued mental retardation was undoubtedly a result of the significant CNS insult and did not affect the final form of the VER. The abnormal ERGs found by Merin and coauthors8l in 51 mentally retarded patients are not easily explained by the data presented. They suggest that the abnormal ERG may reflect a similar disease process affecting the retina and brain. Only two of their patients had extinct ERGs and were subsequently diagnosed as having Hallgren's syndrome (retinitis pigmentosa, congenital deafness, mental retardation, and vesticulocerebellar ataxia).82 Shapira and colleagues80 found 36 of 48 mentally retarded children to have extinct or abnormal VERs. Twenty-four of these were abnormal on the basis of either subnormal potentials or lengthened latencies. They found no correlation between the type of VER and any particular clinical finding. They did not find the severity of retardation to be a factor in the VER abnormality. Our findings of normal VERs and ERG in a significant number of patients with severe mental delay would seem to indicate that mental retardation, per se, does not lead to changes in these parameters. A possible explanation for the findings reported by Shapira and associ-


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TABLE XIV: SUMMARY OF FINDINGS IN PATIENTS WITH NORMAL ERG/NORMAL VER

RESULT OF OPHTHALMIC EXAMINATION

NO OF PATIENTS

Normal

61

Cataract

29

Optic nerve disease

34

Nystagmus Other

10 37

Total

CONCLUSION

PROGNOSIS

"Perceptual blindness" May improve with time if acute in onset and early in life Retina, optic nerve Acceptable for cataract intact surgery Central visual fibers ? Probably better than if intact no VER Probably congenital Stable vision Visual system intact Stable or possibly improvable

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ates80 is that the poor attention and general lack of cooperation usually present in such children without any other significant CNS or retinal defect can certainly lead to significant changes in the VER.38 Many of our patients had significant defects in their visual system leading to abnormal ERG or VER responses, which were an indirect rather than a direct consequence of their mental retardation. The usefulnes of ERG/VER testing in children has been shown by many other authors and is borne out by our experience utilizing skin electrodes in these unsedated children. Unfortunately, we were not able to follow all our patients and to report on the final outcome of each patient. Many patients in this study were lost to follow-up because they died or moved to another part of the state. Many of the patients we examined subsequently were seen because their visual status had improved and they were brought back for retesting. This undoubtedly gives us a bias in our experience. Nevertheless, we believe that some conclusions can be drawn from this series of patients. Tables XIV through XVII summarize our experience and may be helpful to others in interpreting the results of their own testing with this interesting, but often frustrating, group of patients. CONCLUSIONS

The use of skin electrodes to record ERGs in unsedated infants and retarded older children is a useful method to determine the electrophysiologic status of the retina. When combined with simultaneous VER testing, it provides two extra parameters of visual assessment that can be extremely helpful in the determination of visual function in these patients.

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France TABLE XV: SUMMARY OF FINI)IN(GS IN PATIENTS WITH NORMAL ERG/ABNORMAL VER

RESULT OF OPIITIIAL-

MIC EXAM INATION Normal

Optic nierve disease

NO OF PATIENTS

39

49

Cataract

2

Other

I

Total

91

CONC(LUSION Damage to central visual pathways

PROGNOSIS

Guarded; poor if chronic and associated with other CNS diseases; fair if acuite and in young patients Central fibers affected Poor if chronic and associated with other CNS diseases ? Optic atrophy Poor ? Cortical disease Visual radiations or Poor cenitral imiacular disease

ERGs are recordable as early as the 12th day of life (and most likely earlier) using skin electrodes. The smaller-amplitude ERG found by this method, as well as the normally smaller amplitude of the infant ERG, is still easily detected. The VER is present as early as the 12th day of life (and most likely earlier) but is best examined using slower stimulation (eg, 2 Hz) than is usually used (4 Hz). The VER may be less complex in infancy and in retarded children than in alert, cooperative adults and may be more easily identified if two waves are compared on the same tracing. Combined ERG/VER testing was successful in detecting visual system abnormalities in a series of 302 patients studied. This method was most helplful in discovering primary retinal disease and visual pathway abnormalities not otherwise found on ophthalmologic examination. Early diagnosis of such conditions is helpful to both the physician and parents as well as to the child. In some cases (eg, Leber's congenital amaurosis or hereditary retinitis pigmentosa) early diagnosis can lead to genetic counseling that may be of great importance both socially and financially to a family. In addition, earlier intervention by local social agencies to provide services and education to children with visual handicaps is of great benefit to both child and family. The ERG is a sensitive and accurate detector of primary retinal disease well before clinical signs of retinal change appear. Its use is indicated in any child presenting with poor visual responses as soon as the problem is recognized. The flash ERG is not useful in the detection of small, central


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TABLE XVI: SUMMARY OF FINDINGS IN PATIENTS WN-ITH ABNORMAL ERG/NORMAL

RESULTS OF OPHTHAL-

NIIC EXAMINATION Retinal degeneration

NO OF PATIENTS

10

Retinal detachment

1

None Other

2 4

Total

17

CONCLUSION Primarv retinal problem or secondary to systemic disease Retinal detachment with some central function remaining Achromatopsia Extensive retinal disease with some central function remaining

N'ER

PROGNOSIS

Poor

Fair Stable ?

vision defects that do not affect the peripheral retina due to the global nature of the retinal response. The use of pattern evoked ERG may have some application in detecting small, central retinal lesions that result in poor central visual acuity. The VER can be a helpful measure of central vision with the ability to detect loss of central acuity with intact peripheral visual fields. In children using an intermittent flash evoked response, the VER is a measure of the intact central visual radiations. It is helpful in determining the cause of visual loss when the ophthalmologic examination is otherwise normal. The diagnosis of cortical blindness is based on loss of VER with normal eye findings. The VER alone does not appear to be a good prognostic guide for return of vision when it is abnormal. Patients with absent VERs and poor visual responses were found to recover nearly full function with return of normal VER. In addition, patients with reasonable visual function (? perhaps not central) were found to have abnormal VERs, indicating a lack of correlation of visual function with the VER in these patients. Patients with poor visual function with normal VERs were thought to have a better prognosis for return of vision following an acute CNS insult. Patients with generalized neurologic deficits and normal VERs were considered to have visual processing abnormalities rather than visual radiation deficits and were called perceptually blind. It is my hope that other ophthalmologists will recognize the usefulness of this method of testing and will utilize it to aid them in the diagnosis of visual problems in children.

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TABLE XVII: SUMMARY OF FINDINGS IN PATIENTS WITH ABNORMAL ER(; AND \'ER

RESU'LT OF OPHTHAL-

NIIC EXANMINATION Normal Retinal detachlnent Cataract

NO OF

PATIENTS 9 2 2

CONCLUSION Leber's conigential amaurosis Retinal abnormalitv with poor remainiing function Combined with detached

PROGNOSIS

Poor Poor Poor

retina

Retrolental fibroplasia Other

Total

2 8

Retina completely degenerated Central retinial artery occlusion, coloboma of retina and nerve, congenital retinal folds with poor fuinction

Poor Poor

23

ACKNOWLEDGMENTS

I would like to thank Dr Burton J. Kushner for allowing me to include some of his patients in this study. I would also like to thank Robert M. Jones, Jacqueline W. Frank, and Sally A. Baumgartner for carrying out the technical portions of this study. REFERENCES 1. Goodman G, Ripps H, Siegel I: Electroretinographv in infants and children, in Apt L (ed): Diagnostic Procedures in Pediatric Ophthalmology. Boston, Little, Brown & Co, 1963, pp 81-106. 2. Du Bois-Reymond E: Cited by Jacobson JH: Clinical Electroretinography. Springfield, Ill, Charles C Thomas, 1961. 3. Dewar J: On the physiological action of light. Nature 1877; 1:453-454. 4. Riggs LA: Continuous and reproducible records of the electrical activity of the human retina. Proc Soc Exp Biol Med 1941; 48:204-207. 5. Granit R: Sensory Mechanisms of the Retina. London, Oxford University Press, 1947. 6. Karpe G: Basis of clinical electroretinography. Acta Ophthalmol (Suppl) 1945; 24:1-118. 7. Arden GB, Carter RM, Hogg CR, et al: A gold foil electrode: Extending the horizons for clinical electroretinography. Invest Ophthalmol Vis Sci 1979; 18:421-426. 8. Einthoven W, Jolly W: The form and magnitude of the electrical response of the eye to stimulation by light at various intensities. Q J Exp Physiol 1908; 1:373. 9. Fishman GA: The Electroretinogram and Electro-oculogram in Retinal and Choroidal Disease. Rochester, Minn, American Academv of Ophthalmology and Otolarvngology, 1975, pp 9-11. 10. De Moifetta V, Spinelli D, Polengli F: Behavior of electroretinographic oscillatory potentials during adaptation to darkness. Arch Ophthalmol 1968; 79:531-535. 11. Lawwill T: The bar-pattern electroretinogram for clinical evaluation of the central retina. Am J Ophthalmol 1974; 78:121-126. 12. Sokol S, Bloom BH: Macular ERGs elicited by checker-board pattern stimuli. Doc Ophthalmnol 1979; 13:299. 13. Maffei L, Fiorentini A: Electroretinographic responses to alternating gratings before and after section of the optic nerve. Science 1981; 211:953-954.


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65. Uchida K, Mitsuvu-Tsuboi NM, Honida Y: Stuidies oni skini-electrode (ERG) in the closedeve state. J Pediatr Ophthalmol Strabismus 1979; 16:62-65. 66. Zetterstrom B: The clinical electroretinogram: IV. The electroretinogram in children during the first year of life. Acta Ophthalinol 1951; 29:295-304. The electroretiniogram in prematurely born children. Acta Ophthalmol 1952; 67. 30:405-408. Flicker electroretinographv in newborni infants. Acta Ophthalmol 1955; 68. 33: 157-166. 69. XVinkelman JE, Horsten GPNM: The ERG of prematture and full-term born inifants dturing their first days of life. Ophthalmnologica 1962; 143:92-101. 70. Horsten GPM, WVinkelman JE: Electrical activity of the retina in relation to histological differentiation in inifants born prematturely and at fuill-term. Vision Res 1962; 2:269-276. 71. Shipley T, Anton NIT: The huiman electroretinogramn in the first day of life. J Pediatr 1964; 65:733-739. 72. Francois J, de Rouick A: The electroretinogram in vouing childreni (single stimtultus, twin flashes and intermittent stimutlation). Doc Ophthalmol 1964; 18:330-343. 73. Barnet A, Lodge A, Armiington JC: Electroretiniograms in newborn hutman infants. Science 1965; 148:651-654. 74. Algvere P, Zetterstrom B: Size and shape of the electroretinogram in newborn infanits. Acta Ophthalmol 1967; 45:399-410. 75. Ellingsoni RJ: Cortical electrical responses to visual stimulatioll in the hiumall inlfant. Electroencephalogr Clin Neurophysiol 1960; 12:663-667. Development of visual evoked responses in htuman infants recorded by a 76. response averager. Electroencephalogr Clin Neurophysiol 1966; 21:403-404. 77. Lodge A, Armingtoni JC, Barnet AB: Newborn inifant's electroretinograms and evoked electroencephalographic responses to orange and white light. Child Dev 1969; 40:267-293. 78. Marg D, Freemani DN, Peltzman P, et al: Vistual actuity development in htuman infants: Evoked potential measturement. Invest Ophthaltnol Vis Sci 1976; 15:150-153. 79. Sokol S, Dobson V: Patterni reversal vistually evoked potenitials in infants. Invest Ophthalinol Vis Sci 1976; 15:58-62. 80. Shapira Y, Szabo G, NMerin S, et al: Electrophvsiological studies of the visual system in mentally retarded children: II. Visuial evoked potentials. J Pediatr Ophthalmnol 1973; 10:223-225. 81. Merin S, Shapira Y, Szabo G, et al: Electrophysiological studies of the visual system in mentally retarded children: I. The electroretinogram. J Pediatr Ophthalmol 1973; 10:217-222. 82. Hallgren B: Retinitis pigmentosa combined with congeniital deafness; with vestibulocerebellar ataxia and mental abnormality in a proportion of cases: A clinical and genetic sttudv. Acta Psychiatr Neurol Scand (Stippl 138) 1959; 34:5-101.

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434

APPENDIX I PATIENTS WITH NORMAL ERG AND VER PATIENT NO

AGE (YR)

SEX

SYSTENIIC CONDITION

DIAGNOSIS

1

9

F

Cataract, congenital uni-

2 3 4 5 6

0.5 13 12 2 2

F

lateral Blindness, perceptual

7

M F F M

Cataract, traumatic

M

Cerebral palsy

Drusen, optic nerve

Rubella syndrome

Glaucoma Cataract, congenital bilateral Optic nerve atrophy Esotropia Cataract, traumatic Cataract, congenital unilateral Blindness, perceptual PHPV Cataract, congenital uni-

8 9

7 2

F F

10 11

3 1

M

12

1

F

13

1

M

Cataract, congenital bi-

14 15

1 1

F F

Cataract, traumatic Cataract, congenital bi-

16 17

3 002

M M

Mental retardation

18

0.1

F

Rubella syndrome

19

0.94

M

20 21

0.5

M F

22 23

2 0.4

24

1.34

25 26

0.49 0.13

M

27

0.31

F

F

lateral Rubella syndrome

Cataract, congenital bi-

lateral lateral lateral Optic nerve atrophy Cataract, congenital unilateral Cataract, congenital bilateral Paresis, third nerve

Amblyopia 0.2

M F M

F

Retrolental fibroplasia Cataract, congenital uniMental retardation

lateral Blindness, perceptual Oculomotor apraxia Esotropia Cataract, congenital unilateral Esotropia Nystagmus Cataract, congenital unilateral Esotropia


435

APPENDIX 1 (Continued) PATIENTS WITH NORMAL ERG AND VER PATIENT NO

AGE

RAW

SEX

28

3

NI

29

2

F

30

0

F

31 32

0.5 0.6

F XI

33 34 35 36 37 38 39 40 41 42 43

1 0.35

F

SYSTEMIC CONDITION

Cerebral palsY

DIAGNOSIS

Hypoplastic optic Esotropia PHPV Cataract PHPV' Cataract

nerve

Blindniess, percepttual Esotropia

Retinial hemorrhage

0.51 0.4 0.4 0.1 7 3 11 1.04

Esotropia

NI

V'itreouis hemorrhage

F NI F

Nystaglnits Blindness, perceptuial Blindniess, perceptuial

Cerebral palsy

Blindness, percepttial Anomaly, optic nerve

NI

F NI

Nvstagmuts

Cataract, acqluired

0.56

F F F

44

0.36

NI

Octulomotor apraxia

45

0.3

F

Exotropia Cataract, congeniital bi-

Cardiovascular disease Blindness, percepttlal Coloboma, optic nierve Nvstagmuis

lateral Esotropia Nvstagitns

46

13

NI

Neurodegenerative

disease

47

0.76

F

48 49

0.56 5

F F

50

0.27

F

51

0.65

F

Hydrocephalus

Esotropia Amblyopia Anomaly, optic nerve Esotropia Blindness, perceptual Esotropia Amblyopia

PHPN7 Cataract, congeniital unilateral Optic inerve atrophy Nystagmus

52

8

F

53

4

NI

Hydrocephaluis

Esotropia Exotropia Blindniess, percepttual

Optic nerve atrophy Esotropia

France

436

APPENDIX

I

(Continued)

PATIENTS WITH NORMAL ERG AND VER PATIENT NO

AGE AR)

SEX

54

0.61

NI

55 56

2 0.63

NI NI

Nl\ental retardation

57

4

F

Cerebral palsy

SYSTEMIC CONDITION

I)IAGNOSIS

Paresis, third nerve Deprivation ambivopia Blindness, perceptual Hvpoplastic optic nierve Esotropia Nystagmus

Blindness, percepttual Esotropia

58

4

NI

Cerebral palsy

59

13

F

Niental retardation

Blindness, perceptuial Esotropia Amblvopia

Cerebral palsv

60 61 62 63 64

8 14 8 18

F F NI

Nlenital retardation

NI

NIental retardation

7

F

65 66 67 68

6 0.48 0.39 11

69 70

5

Nlental retardationi

NI NI F F

Hydrocephalus Hydrocephalus

F

Hydrocephalus

Nelental retardat ion

Ni

72 73 74 75 76 77

9 5 0.51 0.8 5 12 1.91 6

NI

Cerebral

F F Ni F

Nlenital retardation Albinism

78 79

2 0.69

NI

80

4

F

81 82

9 3

F NI

83

4

71

NI NI

palsy

F

84I

Cerebral palsy Nlental retardation

Hydrocephalus

Hypoplastic optic nierve Optic nerve atrophy Optic nerve atrophy Blindniess, perceptual Opaqcue cornea Glaucoma Hypoplastic optic nierve Exotropia Optic nerve atrophy Optic nerve atrophy Optic nerve atrophy Blinidness, percepttual Exotropia Optic nierve atrophy Esotropia Amblyopia Optic nerve atrophy Blindness, perceptual Blindness, perceptual Nystagmtus Blinidness, perceptual Nvstagmus Nystagmus Esotropia

Nystagmrus Colobomia, optic nierve Cataract, congeniital unilateral Blindness, perceptuial Cornieal opacity Ny stagmus Blindness, perceptual


437


AGE (YR)

SEX

84

0.67

M

85

1.21

M

SYSTEMIC COND)ITION

Cerebral palsv Mental retardation Mental retardation MNicrocephalus

F

86 87 88 89 90 91

13 9 3 5 2 1.28

92 93

0.24 2

M

94

3

NI

95 96 97

3 4 3

M

Ni

F

Seizures

Mental retardation Mental retardation I)eafness

M M

M

M

Seizures Cerebral palsy

Cerebral palsv

M

F

M icrocephalus Mental retardation

98 99 100 101

0.88 0 0.86 7

102

3

F

103

3

F

104

3

F

105

0.31

F

106

1.02

F

Seizures

107

0.65

M

Cerebral palsy

108 109

6 2

M M M

F

Mental retardation Seizures Cerebral palsy Mental retardation Mental retardation Multiple congenital anomalies

DIAGNOSIS

Optic nerve atrophy

Blindness Exotropia Blindness, perceptual Blindness, perceptual Blindness, perceptual Pigmentary retinopathv Optic nerve atrophy Blindness, perceptual Esotropia Blindness, perceptual Nystagmus Esotropia Blindness, perceptual Myopia Optic nerve atrophy Blindness, perceptual Corneal uilcer

Hypoplastic optic nerve Blindness, perceptual Blindness, perceptual Blindness, perceptual

Hypoplastic optic nierve

Seizures

M M

Cerebral palsy Mental retardation

Blindness Vitreous hemorrhage Cataract Cataract, congenital bilateral Coloboma, optic nerve

Blindness Nystagmus Optic atrophy Exotropia Blindness, perceptual Optic nerve atrophy Esotropia Nystagmus

France

438

APPENDIX

1

(Continued)

PATIENTS WITH NORMAL ERG AND VER PATIENT NO

AGE (YR)

SEX

110

2

M

111

2

M

112 113

1.71 9

SYSTEMIC: CONDITION

Family history Leber's congeniital

DIAGNOSIS

Normal eve

amaurosis

114

11

M M

F

F

115 116 117 118 119 120

5 0.26 0.85 4 5 5

121

3

F

122

0.92

F

123

5

F

124 125 126

2 1.75 0.79

127 128

1.49 0.41

129

4

Ni

F F M

M

Family history Retinitis pigmentosa

Cataract, congenital unilateral Axenfeld's anomaly Normal eye

Hvpermetropia Blindness, perceptual Astigmatism Ptosis, acquired Cardiovascular disease Blindness, perceptual Blindness, perceptual Hydrocephaluis Hypoplastic optic nerve Blindness, perceptual Leukemia Blindness, perceptual Seizures Optic nerve atrophy Seizures Exotropia Blindness, perceptual Mental retardation Esotropia Blindness Microcephalus Mental retardation Optic nerve atrophy Seizures

M M

F M

F F F F

130 131 132

14 6 0.54

M

133

0.84

M

134 135

0.23 7

Mental retardation Cerebral palsy Mental retardation Seizures Sturge-Weber svndrome Down's syndrome Mental retardation Microcephalus Mental retardation Mental retardation Seizures Hydrocephalus

Blindness, perceptual Exotropia Optic nerve atrophy Blindness, perceptual Glaucoma

Nystagmus Blindness, congenital Cataract Blindness, perceptual Exotropia Optic nerve atrophy Hysteric, V Blindness, perceptual

Seizures

Hydrocephalus Mental retardation

M

F

Mental retardation

Blindness Esotropia Nystagmus Blindness, perceptual Blindness, perceptual


439

APPENDIX 1 (Continued) PATIENTS WITH NORMAL ERG AND VER

PATIENT NO

AGE (YR)

SEX

136 137

0.82 0.47

M F

138

2

F

SYSTENIIC CONDITION

Seizures

DIAGNOSIS

Blindness, perceptual Blindness, perceptual

Mental retardation

Retrolental fibroplasia

Esotropia Amblvopia 139

2

140 141 142

7 8 0.17

143

3

F

144 145

3 0.71

M

146

0.29

M

Retrolental fibroplasia Seizures

Esotropia Optic nerve atrophy Aniridia, F PHPV Cataract

F

Mental retardation Microcephalus Mental retardation Seizures Cerebral palsy

Cataract, traumatic Endophthalmitis Blindness, perceptual Blindness, perceptual Blindness, perceptual

Seizures

147

0.23

F

148

0.23

M

149 150

2 1.03

M

151

3

F

152 153

0.6 2

F

154 155 156

0.11 3 3

157

0.27

Multiple congenital anomalies Mental retardation Multiple congenital anomalies

M

Seizures Cerebral palsy Mental retardation Multiple congenital anomalies

Optic nerve atrophv

Blindness, perceptual

Photophobia Optic nerve atrophy Blindness, perceptual

Seizures

M

M M

M

Hydrocephalus Mental retardation Seizures Mental retardation Seizures

PHPV Blindness, perceptual Normal eye Blindness, perceptual Cataract, congenital unilateral Cataract, congenital unilateral Microphthalmus

France

440


AGE (YR)

SEX

158

5

F

159

0.23

M

160

0.76

M

161 162 163

2 4 2

M

164 165

1.08 0.83

166

1.23

167 168

0.19 3

169

1.03

F

170

5

F

171

0.76

M

SYSTEMIC CONDITION

Mental retardation Cerebral palsy Neurologic disease Cerebral palsy Neurologic disease Mental retardation

F F

Cerebral palsy Cerebral palsy Mental retardation

M

F

Mental retardation Microcephalus

F M M

Microcephalus Cerebral palsy Hydrocephalus Mental retardation Cerebral palsy

DIAGNOSIS

Blindness, perceptual Blindness, perceptual

Blindness, perceptual Nystagmus Blindness, perceptual Optic nerve atrophy

Nystagmus Blindness, perceptual Peters' anomaly Glaucoma Nystagmus Blindness, perceptual Blindness, perceptual Esotropia Nystagmus Blindness, perceptual

Seizures

Mental retardation Seizures

Blindness, perceptual


441

APPENDIX 2 PATIENTS WITH NORMAL ERG AND ABNORMAL VER PATIENT No

1 2 3 4 5 6

7 8 9

AC,E YR)

14 11 6 7 5 3

0.8 12 1(

SEX

NI NI F F NI F NI

SYSTEMIC CONIDITION

Menital retardation Cerebral palsy Cerebral palsy Menital retardationi

Mental retardationi Mental retardationi Seizures Cerebral palsy Cerebral palsy

NI

Mental retardationi

M

Cerebral palsy

DIAGNOSIS

Optic nerve atrophy Optic nierve atrophy Optic nerve atrophy Optic nerve atrophy Cortical blindness Optic nerve atrophy Exotropia Optic nerve atrophy Cortical blindness Cortical blinidniess

Menital retardationi 10 11

0.75 0.53

NI F

Cerebral palsy

Microcephaly Menital retardationi Mental retardationi

Cortical blindness Bilateral congeniital cat-

aract 12

2

F

13

5

F

14 15

4 1

Ni M

16 17 18 19 20 21 22 23

1.06 1 0.88 2 0.6 2 1.16 6

F F NI F F M M F

24 25 26 27 28 29 30 31

0.51 0.47 0.17 0.71 10 3 1.04 8

F M F NI F M F F

Microcephaly Nlenital retardation

Cortical blindness

Cortical blindness Exotropia Optic nerve atrophy

Seizuires

MeIetal retardationi

Cortical blindness Optic nerve atrophy Esotropia

Cerebral palsy Seizures

Mental retardationi Hydrocephaltis

Mental retardation Cerebral palsy Nlental retardationi

Seizures

Menital retardation

Cortical blindness Cortical blindness Cortical blindness Optic nerve atrophy Optic nerve atrophy Optic nerve atrophy Optic nerve atrophy Cortical blindness Cortical blindness Cortical blindness Cortical blindness Cortical blindness Cortical blindness Cortical blindness Hypoplastic optic nerve Optic nerve atrophy Nystagmus

442

France APPENDIX 2 (Continued) PATIENTS WITH NORMAL ERG AND ABNORMAL VER

PATIENT NO

32 33

AGE (YR)

1.11 9

SEX

F M

SYSTENIIC CONDITION

Microcephaly Congenital toxoplas-

DIAGNOSIS

Optic nerve atrophy Cortical blindness

mosis

34

14

35 36 37

8 7 0.9

38 39

0.01 6

M

Rubella syndrome Mental retardation

Cataract Optic nerve atrophy

F M

Mental retardation

F

Mental retardation

Seizures

M

Mental retardation Mental retardation Cerebral palsy Mental retardation

4 3 2

M

Mental retardation

44

4

F

45

0.56

F

46 47

0.4 0.08

40

10

41 42 43

M M

F M

Retinal detachment Esotropia

Cerebral palsy

Cortical blindness Optic nerve atrophy Cortical blindness Optic nerve atrophy Cortical blindness Exotropia Optic nerve atrophy Nystagmus Optic nierve atrophy Hypoplastic optic nerve Cortical blindness

Seizures

Craniometaphvseal dysplasia

M M

Multiple congenital

Exotropia

Cortical blindness Esotropia Hypoplastic optic nerve Microphthalmus

anomalies

Mental retardation 48

4

F

49

6

M

50

2

M

51 52 53 54 55 56

3 9 0.28 0.31 1.96 5

57

58

F

Microcephalus Mental retardation Hydrocephalus Mental retardation Hydrocephalus

M M M M

F

Mental retardation

3

M

Mental retardation

11

F

Optic nerve atrophy Exotropia Cortical blindness Esotropia Optic nerve atrophv Optic nerve atrophy Cortical blindness Hypoplastic optic nerve Cortical blindness Cortical blindness Optic nerve atrophy Cataract Optic nerve atrophy Esotropia Hypoplastic optic nerve


443

APPENDIX 2 (Continued) PATIENTS WITH NORMAL ERG AND ABNORMAL VER PATIENT NO

AGE (YR)

SEX

Optic nerve atrophy Esotropia

59

5

F

60 61 62

2 0.29 3

M

63 64 65

6 0.12 2

F F

66 67

7 0.35

M

68 69

9 0.53

F

Seizures

F

Seizures

70 71 72

6 6 1.63

Seizures

F M

M

DIAGNOSIS

SYSTEMIC CONDITION

Mental retardation

Cerebral palsy

M

Hydrocephalus

Mental retardation

Cortical blindness Hypoplastic optic nerve Cortical blindness Optic disc anomaly Optic nerve atrophy Optic nerve atrophy Cortical blindness Esotropia Optic nerve atrophy Optic nerve atrophy Exotropia Optic nerve atrophy Cortical blindness Exotropia

Hypoplastic optic nerve Cortical blindness Optic nerve atrophy

Seizures 73 74

0.86 0.24

75 76

7 2

77

8

78 79

9 0.7

M

80

0.94

F

81

5

M

82 83 84

2 1.76 0.81

F F

85 86

1.62 2

Seizures

Cortical blindness Hypoplastic optic nerve Nystagmus

Seizures

M

Mental retardation Hydrocephalus Cerebral palsy Mental retardation Cerebral palsy Mental retardation

Cortical blindness Coloboma optic nerve Esotropia Optic nerve atrophy Glaucoma Hypoplastic optic nerve Hypoplastic optic nerve Optic

nerve

atrophy

Cortical blindness

Hypoplastic optic

Hydrocephalus Sturge-Weber syndrome

nerve


Seizures M

F

Cerebral palsy Mental retardation Hydrocephalus


France

444

APPENDIX 2 (Continued) PATIENTS WITH NORMAL ERG AND ABNORMAL VER PATIENT NO

AGE (YR)

SEX

87

1.84

M

Hydrocephaltis

M

Microcephalus Mental retardation

88

10

89

1.11

F

90

3

M

91

2

M

SYSTENIIC CONDITION

Cerebral palsy Mental retardation

DIAGNOSIS

Optic nerve atrophy Nystagmus Cortical blindness Esotropia Hypoplastic optic nerve Exotropia Optic nerve atrophy Esotropia

Nystagmus Cortical blindness Exotropia

APPENDIX 3 PATIENTS WITH ABNORMAL ERG AND VER PATIENT NO

AGE (YR)

SEX

1

11.00

M

2 3 4 5

0.40 6.00 2.00 0.23

M

6

7.00

F

7 8

7.00 8.00

F F

9 10 11

6.00 6.00 6.00

M

12 13

10.00 8.00

F F

14 15 16 17

2.00 0.33 6.00 7.00

M

F M

F M

F M M M

SYSTEMIC CONDITION

DIAGNOSIS

Batten-Mayou disease Retinal degeneration Esotropia Renal disease Retinal degeneration Retinitis pigmentosa Batten-Mavou disease Retinal degeneration Microcephalus Retinal detachment Mental retardation Latirence-Moon-Biedl Retinal degeneration syndrome Mental retardation Retinitis pigmentosa Lauirence-Moon-Biedl Retinial degeneration syndrome Mental retardation Retinitis pigmentosa

Achromatopsia Stationary night blindness Batten-Mayou disease Retinal degeneration Mental retardation Progressive external Neurologic disease ophthalmoplegia Diabetes

Achromatopsia Retrolental fibroplasia Hydrocephalus Batten-Mayou disease Retinal degeneration Retinitis pigmentosa


445

APPENDIX 4

PATIENTS WITH ABNORMAL ERG AND VER SYSTEMIC CONIDITION

DIAGNOSIS

PATIENT NO

A(;E (YR)

SEX

1

0.2

M

PHPV, anterior and pos-

2

0.15

NI

Leber's congenital

3

(.1

M

Coloboma of iris and ret-

terior

amaurosis

4

1.31

F

inla Microphthalmia Corneal opacity Leber's congenital

5 6

1.64 1.12

F F

Retrolental fibroplasia Leber's congenital

amaurosis

arnaurosis 7

14

F

8

8

F

NMental retardation

Retinal detachment, traumatic Leher's congenital

Mental retardation

amaurosis

11

3

M

Retinial degeneration Leher's congenital amaurosis Leber's congenital

12

4

M

Leber's congenital

13

0.4

M

14

2

NI

15

3

F

9 10

16 0.57

M

F

amaurosis

amaurosis

Mental retardation Seiztres

Central retinal artery occlusioll Optic nerve atrophy Leber's congenital amaurosis

16

17

0.39 15

F F

Mental retardation Seiztires

18 19

1.42 3

M

20 21

4 0.2

F NI

Cataract, traumatic Retinal detachment, traumatic Congenital retinal fold Cataract, traumatic Retinal detachment, traumatic Retrolental fibroplasia Cataract, traumatic Retinal degeneration

Achromatopsia Congenital retinal fold

France

446

APPENDIX 4 (Continued) PATIENTS WITH ABNORMAL ERG AND VER PATIENT NO

AGE (YR)

SEX

22

2

F

23

20

M

SYSTEMIC CCONDITION

Rubella svndrome Mental retardation

DIAGNOSIS

Cataract, bilateral congenital Retinial detachment Microphthalmia Leber's congenital aimalirosis