Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

Arch. Dis. Childh., 1968, 43, 658.

Role of in Investigation of Impaired Visual Function in Childhood KENNETH WYBAR and BRIAN HARCOURT From The Hospitalfor Sick Children, Great Ormond Street, London

Visual function is difficult to assess in young oculography, and visually evoked cortical responses. children because their limited ability to understand In this paper only electroretinography is discussed. and communicate determines the necessity of When the healthy is stimulated by a bright adopting, to a large extent, objective methods of flash of light a complex series of changes is induced examination and investigation (Harcourt and Wybar, in the electrical potential of the retinal elements. 1966). This also applies sometimes to older children The sum of these changes may be detected by who are not sufficiently co-operative in their placing an active electrode on the by means subjective responses. of a contact lens, and also earth and reference The afferent visual system is a complex mechanism electrodes on the skin of the face (Fig. 2). When (Fig. 1), and a dysfunction of any of its components amplified and recorded these changes are summated may cause a profound visual defect. When a clinical to form the electroretinogram (ERG) which has examination of a young child suggests that the two principal features (Karpe, 1945): an initial vision is defective the site of the impairment may a-wave of negative potential and a subsequent

be obvious (as in some disorder of the ocular media, b-wave of positive potential (Fig. 3). These electrical by copyright. like a cataract), but sometimes it is not apparent changes represent a mass response from all the because of an absence of any objective clinical elements in the outer retinal layers. The experi- evidence of an ocular disorder. There are several mental investigation of the alterations which occur reasons for this difficulty. In some cases there may in the wave-form of this response under the be a gross functional abnormality of the retinal influence of selective retinotoxic drugs suggests elements without any obvious ophthalmoscopic that the a-wave is due principally to changes evidence of retinal disease, and in others there may occurring in the electrical potential of the outer be an optic atrophy difficult to distinguish from the segments of the retinal receptors as the result physiological pallor of the optic discs commonly of light stimulation, and the b-wave is due princi- seen in normal young children. Furthermore, pally to changes in the bipolar cells (Noell, 1959). http://adc.bmj.com/ there may be a dysfunction of the optic radiation The changes in potential which occur in the gang- or visual cortex which is not reflected in any lion cells of the retina and in the optic nerve changes in the pupillary light reflexes or the optic fibres after stimulation of the retina by light form discs because of the suprageniculate nature of the no significant part of the ERG response, so that lesion, or the child may show little or no interest it is normal in cases of optic atrophy despite a in visual stimuli simply because of a gross degree profound loss of vision. The amplitude of the re- an of mental retardation. Finally, older child's sponse is proportional to the total number of on September 28, 2021 by guest. Protected inability to give a correct response in subjective retinal elements stimulated, and because of the visual tests may be due to a state of hysteria. preponderance of the rods over the cones the total In these conditions in early childhood the normal response is due principally to rod activity; this is clinical methods ofexamination are often inadequate illustrated by the increase in the amplitude of the for the assessment of visual function and for the response which follows a progressive dark adapta- localization of the visual defect so that additional tion because this enhances the light sensitivity forms of investigation are necessary; these include and the electrical activity of the rods. electrodiagnostic methods which are applied to The amplitude and wave-form of the ERG re- the visual apparatus-electroretinography, electro- sponse may be abnormal in several different ways; it may be inverted if only the negative a-wave is present, subnormal ifboth the a-wave and the b-wave Received May 20, 1968. are diminished in amplitude, or absent. At birth 658 Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

Eilectroretinography in Investigation of Impaired Visual Function in Childhood 659

FIG. 1. A diagrammatic representation of the affer- ent pathway, demonstrating 20 the three orders of sensory neurones involved in the >< >--< relay of information be- tween the retinal receptors (rods and cones) and the visuo-sensory cortex. (1) The retinal receptors; (2) the bipolar cells (first order neurones); (3) the optic nerve fibres, passing without delay into the optic chiasma and the optic tract (second LGB order neurones); (4) The optic radiation (third order -l neurones). L.G.B. = the lateral geniculate body; V.S.C. = the visuo-sensory cortex. by copyright. http://adc.bmj.com/ on September 28, 2021 by guest. Protected

FIG. 2. Electroretinography in a young child. The contact lens bearing the active electrode and the reference and earth electrodes have been applied under general anaesthesia. Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

660 Wybar and Harcourt in adults and in older children by a voluntary O.4 effort to keep the steady or by the maintenance of a steady fixation of a dim source of light by the

0-3 - which is not under examination, but this is seldom possible in young children because of their natural apprehension and because of the Miilivoits slight discomfort which is caused by the insertion of the contact lens. It follows that the investigation requires general anaesthesia in children under the o-20 age of 6 years, and sometimes in older children .+. who are nervous or mentally retarded. The investi- :V: a gation under general anaesthesia can be combined ..v with a thorough examination of the ocular media and fundi, and with a photographic recording - ^-e.S .I.. A I '. of any abnormal appearances. Preliminary dilatation 0-1 ...... of the pupils with cyclopentolate 1% drops is .I carried out and the ERG response in the light- Light flash; A. adapted state is recorded. The increase in the amplitude of the response which occurs during FIG. 3. A diagrammatic representation* oz.-of

Electroretinography in Investigation of Impaired Visual Function in Childhood 661

FIG. 4. Electroretinography under general anaesthesia. The child's head is surrounded by an opaque cage in which is incorporated the light flash source. The eyes are dark adapted despite the normal illumination of the examination room. also seldom show any abnormality of the fundi), pathological alterations in the retinal pigment pattern,

because the latter has a normal ERG. particularly in the macular regions of both eyes, with by copyright. The following case reports demonstrate the retinal arterial attenuation and some optic atrophy. value of the ERG. A very small inverted ERG response was obtained with an intense light stimulus. A diagnosis of Leber's congenital amaurosis (congenital tapeto-retinal degenera- Case Reports tion) was made. There was no family history of a similar condition. Case 1. This girl was born in August 1966 of unrelated parents. Her mother's pregnancy had been Case 2. This female child was born in August 1959 uneventful and delivery was normal. She was referred of unrelated parents. She developed whooping cough at the age of 4 months because the parents suspected at the age of 2 months, and from that time her parents that her vision was defective. On examination no re- noticed a marked unsteadiness of her eyes and poor http://adc.bmj.com/ sponses were elicited to moving lights or targets, and responses to visual stimuli. At the age of 10 months the pupillary light reflexes were noted to be inconsistent thechildwas examined atThe Hospital for SickChildren, and sluggish. The child was admitted to The Hospital Great Ormond Street. She was found to have a coarse, for Sick Children, Great Ormond Street, for a general rapid, pendular nystagmus in all directions of gaze investigation, and her mental and physical development and poor ocular fixation and following responses. was found to be within normal limits for her age. Photic revealed no abnormality, and a stimulation during the recording of the standard diagnosis of idiopathic congenital nystagmus was made. electroencephalogram (EEG) revealed no abnormality. Despite a considerable visual handicap, the child was The eyes were examined under general anaesthesia, able to attend a normal school and at the age of 7 years on September 28, 2021 by guest. Protected and the fundi showed marked tigroid features with some her visual acuity using a telescopic visual aid was 3/36 scattered pigment disturbance, but there was no retinal for distant and N 10 for near fixation with each eye. arterial attenuation or optic atrophy. The ERG was The nystagmus at that stage was unchanged in character absent in each eye. and was associated with a variable alternating divergent The child's condition was reviewed at the age of squint. The pupillary light reflexes were rather sluggish 8 months. There were marked roving eye movements but the fundi were still normal in appearance, apart and a variable alternating divergent squint. No ocular from a very slight attenuation of the retinal arteries. fixation or following responses could be elicited using The ERG showed an absence of any recordable response moving targets; the pupillary light reflexes were sluggish from either eye. A diagnosis of congenital tapeto- and an ophthalmoscopic examination revealed some retinal degeneration was made. The patient's elder indefinite attenuation of the retinal arteries. At the age brother had normal vision, but her younger brother was of 14 months there were still no responses to visual found to suffer from a similar disorder when he was stimuli and ophthalmoscopic examination showed brought to the hospital in 1964 at the age of 6 months. Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

662 Wybar and Harcourt by copyright.

FIG. 5. Juvenile tapeto-retinal degeneration. A drawing of the right fundus of Case 3 at the age of 10 years. The pathological features are a pallor of the optic disc, marked attenuation of the retinal arteries, and in the retinal periphery an abnormal stippled pigmentation.

Case 3. This male child was born in November of the image of the object of regard on to an area of the 1957 of unrelated parents. When he was 6 years old retina above the fovea. The ocular media and fundi from some attenuation his parents and teachers first suspected that his vision were normal in appearance apart http://adc.bmj.com/ was abnormal, and at the same time he began to have of the retinal arteries and a slight pallor of the optic difficulty in concentrating at school, appearing to 'day- discs. The ERG was carried out without sedation and dream' much of the time. He was referred to another no responses were elicted even when using very intense hospital where it was found impossible to make any light stimuli. A diagnosis of juvenile tapeto-retinal accurate subjective assessment of his visual acuity. degeneration was made. Since then the child's visual No abnormality was noted on examination of the ocular acuity has deteriorated very markedly, and in September media and fundi, and in view of his highly emotional 1967 it became only counting fingers; by this time there behaviour it was suspected that his visual symptoms were ophthalmoscopic signs of a tapeto-retinal degenera- on September 28, 2021 by guest. Protected were hysterical in origin and he was referred for a tion but not in proportion to the gross visual deficit. psychiatric opinion. During the next year he developed further symptoms which suggested a real visual deficit, Case 4. This girl was first seen in December 1964 holding reading matter very close to his face and later when she was 7 years of age, because of an impairment appearing to gaze over the top of objects which he was of her vision which had been suspected when she failed attempting to fix. His mother also noticed that his visual to pick up objects from the floor as quickly as her difficulties were particularly severe in conditions of younger brother. Her distant vision in each eye was dim illumination. He was referred to The Hospital reduced to 6/18, but the close reading vision was normal for Sick Children in January 1966 for a neurological (N 5) in each eye though this was achieved with some opinion. At that time the vision in each eye was assessed difficulty particularly with the right eye. She was as 6/9 using the 'E' test, but there was found to be a found to have a diffuse pigmentary disturbance of the considerable constriction of the peripheral visual fields macular area of each eye, with an exposure of some on confrontation testing. In addition a tendency to an of the underlying choroidal vessels, suggesting some eccentric type of fixation was noted with the projection form of macular dystrophy, and in other respects the Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

Electroretinography in Investigation of Impaired Visual Function in Childhood 663 fundi were normal and there was no defect of the peri- as an isolated event without carrying out this pheral visual fields. investigation. She was seen again three years later, and there were Though, unhappily, it is at the present time then signs of a widespread disturbance of the retina, impossible to offer any specific treatment for the with a generalized attenuation of the retinal arteries and an accumulation of scattered pigmentary deposits arrest or reversal of tapeto-retinal degenerative in the equatorial and peripheral parts of each retina, changes, it is of great importance that their presence, quite apart from an increase in the macular degenerative severity, and extent should be determined at the changes. The corrected vision of the right eye was earliest opportunity, because the distinction between 6/24 and N 8, and of the left eye 'counting fingers' congenital idiopathic nystagmus, macular dystrophy, and N 18. It was evident that she had a widespread and congenital or juvenile retinitis pigmentosa tapeto-retinal degeneration, and this was confirmed allows an accurate long-term visual prognosis to during an examination under general anaesthesia by be made in early childhood, and also gives valuable the finding of an ERG response of extremely low amplitude in each eye. A further point of interest in information in genetic counselling. A child suffering this case is the occurrence of a widespread tapeto- from an idiopathic nystagmus in the absence of retinal degeneration in a cousin (the daughter of her any retinal abnormality is likely to be capable of mother's brother who married a cousin of her father). education at a normal school because, despite the impaired distant visual acuity, the close reading Discussion vision is usually good and the condition is stationary The cases described confirm the value of electro- or may even tend to improve with age (Wybar, retinography as an objective method of investigation 1968). In contrast, as the degenerative process which demonstrates quite clearly that the cause ofthe is progressive, a tapeto-retinal degeneration which defective vision is a widespread retinal dysfunction. clinically may resemble an idiopathic nystagmus In all the cases there was an indication of a likely in early childhood carries a much worse long-term visual impairment; a poor visual response, an prognosis so that there is an ever-increasing unsteady ocular fixation, a pendular nystagmus, visual handicap, and education at a school for the or roving eye movements. But there was nothing to partially sighted or blind is usually necessary. by copyright. confirm this on straightforward examination such Similarly, a retinal dysfunction limited to the as ophthalmoscopy or retinoscopy except for an macular area alone carries a much better prognosis impairment of the pupillary light reflexes. This than a dysfunction affecting the whole retina, accounted for the difficulty in reaching a precise because the retention of peripheral visual function diagnosis on clinical grounds alone, so that the permits a considerable degree of visual indepen- preliminary diagnosis was sometimes at fault. dence, and also allows reasonably good reading For example, Case 2 was thought initially to be vision when a telescopic visual aid is used which simply a congenital idiopathic nystagmus because magnifies print sufficiently to allow the retinal nystagmus was the predominant symptom, and image to fall outside the defective macular area. Case 3 was considered for a time to be a case of Congenital and juvenile forms of tapeto-retinal http://adc.bmj.com/ hysteria because of the delayed and insidious onset degeneration are usually inherited as autosomal of the visual symptoms which were superimposed on recessive traits, and an early diagnosis ofthe disorder a considerable emotional disturbance. Case 4 allows the parents to have the benefit of genetic illustrates a slightly different problem as the initial counselling at a stage when they are likely to con- symptoms suggested a visual defect affecting sider having other children. only the central portion of the visual field so that It should be noted that electroretinography is a macular dystrophy was a reasonable assumption, of great value also in children who are suspected on September 28, 2021 by guest. Protected but the near extinction of the ERG responses at a of having a tapeto-retinal degeneration because of later stage indicated that the retinal abiotrophic an obvious pigmentary disturbance in the fundi. process was much more profound and widespread There are several conditions, quite apart from than was initially apparent on clinical examination. retinitis pigmentosa, which cause a pigmentary This emphasizes the fact that a tapeto-retinal retinopathy in childhood, notably rubella retino- degeneration in children may involve the central pathy, syphilitic chorioretinitis, post-traumatic part of the retina before showing any obvious retinal pigmentation, and toxic retinopathy, but signs of an involvement of the peripheral parts; an early extinction of the ERG response occurs it is likely, however, that even in the early stages only in retinitis pigmentosa. Furthermore, a tapeto- the electroretinogram provides an indication of the retinal degeneration in a child is not always an more widespread nature of the disorder, and it is isolated event, so that its accurate determination unwise to regard a macular dystrophy in a child may reveal the pattern of other abnormalities, Arch Dis Child: first published as 10.1136/adc.43.232.658 on 1 December 1968. Downloaded from

664 Wybar and Harcourt particularly in suchhereditary disorders as Hallgren's dysfunction which may be only one aspect of a syndrome, Cockayne's syndrome, and Refsum's widespread hereditary degenerative disorder. The disease, in which retinitis pigmentosa is only study of visually evoked cortical responses is one aspect of a widespread degenerative process. another form of electrodiagnostic investigation Electroretinography is limited in its potential which yields additional information about the as a diagnostic tool because it gives information functional integrity of the visual pathways, but the only about the function of the retinal part of the details ofthis method are not included in the present afferent visual pathway. But other forms of electro- discussion. diagnostic investigation are becoming available which show promise of yielding additional informa- tion about the function of other portions of the We should like to thank Dr. G. Pampiglione, Dr. Geoffrey Arden, and Miss Joan Behrman for their afferent visual system, particularly the recording invaluable help in making possible the electrodiagnostic of visually evoked cortical responses, which forms parts of these investigations. We should also like to part of our electro-diagnostic assessment of visual thank Dr. John Wilson for allowing us to publish defects in young children though it is outside the Case 3 which we examined initially during admission to the Neurological Unit of The Hospital for Sick scope of this paper. Children, Great Ormond Street. The work of one of us (B.H.) as Research Fellow in Conclusion Paediatric is sponsored by a grant which has been made available to the Institute of When there is apparent clinical evidence of Ophthalmology by the Variety Club of Great Britain; impaired visual function in a young child, in the grateful acknowledgement is made ofthis. The electrodiagnostic instruments have been made absence of any obvious signs of an ocular ab- available to us by the generosity of a grant from the normality, objective methods of investigation are People Newspaper for research into 'Blindness in necessary in order to confirm the impairment and Infancy'. to localize its cause, or in order to refute the sugges- This work has been supported by a generous grant tion of an impairment. Electroretinography deter- from a gentleman who wishes to remain anonymous, and a grant from the Forest of Arden Lodge, in memory by copyright. mines the cases in which the visual defect is due of the sacrifice of the children of Aberfan. to a widespread retinal dysfunction. Thanks are due to the Institute of Child Health for help with these grants, and to Mr. T. Tarrant of the Medical Illustration Department of the Institute of Summary Ophthalmology for preparing the fundus painting shown The physiological basis and the practical tech- in Fig. 5. nique of electroretinography as applied to young REFERENCES children are described. Four cases are reported Harcourt, R. B., and Wybar, K. (1966). The determination of which illustrate the value of this objective method blindness in infancy. Trans. ophthal. Soc. U.K., 86, 37. of investigation in the diagnosis of congenital and Karpe, G. (1945). The basis of clinical electroretinography. Acta ophthal. Kbh.), Suppl. 24. http://adc.bmj.com/ juvenile forms of tapeto-retinal degeneration, which Leber, T. (1869). Ueber Retinitis pigmentosa und angeborene in their early stages may produce a widespread Amaurose. Albrecht. v. Graefes Arch. Ophthal., 15, (3), 1. Noell, W. K. (1959). The visual cell: electric and metabolic mani- functional abnormality of the retinal receptors festations of its life processes. Amer. J. Ophthal., 48, Suppl. without any obvious signs of retinal disease on 347. Winkelman, J. E., and Horsten, G. P. M. (1962). The ERG of ophthalmoscopic examination. This investigation premature and full-term born infants during their first days is also useful in distinguishing between primary of life. Ophthalmologica (Basel), 143, 92. in child- Wybar, K. C. (1968). Nystagmus in childhood. In Transactions and secondary pigmentary retinopathies of the First International Congress of Orthoptists, p. 249. Kimpton, hood, and in drawing attention to a tapeto-retinal London. on September 28, 2021 by guest. Protected