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ARTICLE
Year : 1956  |  Volume : 4  |  Issue : 2  |  Page : 19-30

Clinical application of electro-retinography


Mahatma Gandhi Memorial Medical College, Indore, India

Date of Web Publication19-May-2008

Correspondence Address:
R P Dhanda
Mahatma Gandhi Memorial Medical College, Indore
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Dhanda R P. Clinical application of electro-retinography. Indian J Ophthalmol 1956;4:19-30

How to cite this URL:
Dhanda R P. Clinical application of electro-retinography. Indian J Ophthalmol [serial online] 1956 [cited 2019 Dec 12];4:19-30. Available from: http://www.ijo.in/text.asp?1956/4/2/19/40827

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In the atomic age, Electro-retinopathy has made very rapid strides in the last few years. Its clinical application is now extended not only to many aspects of ophthalmology but even of general medicine.

The first record of retinal action current is attributed to the famous physio­logist Holmgren (1865), but studies on human beings have only been attempted after the second World War. The first human electro-retinogram was recorded by Linsley and Hunter (1939). Prof. Gosta Karpe at the Stockholm University is the pioneer in human electro-retinography and his exhaustive treatise on "The Basis of Clinical Electro-retinography, (1945) was the first passport for the entry of this delicate method of investigations into systemic ophthalmology and his observation of extinguished electro-retinogram in cases of retinitis pigmentosa is now considered a diagnostic feature. "Electro-retinography in cases of Night Blindness" by Lorrin A. Riggs (1954) has been of particular interest to me because of my studies on cases of night-blindness due to Vitamin-A deficiency. In addi­tion its prognostic and diagnostic utility has been amply proved by studies in cases of siderosis bulbi and occlusion of central retinal artery and vein". "Electro­retinographic Studies in Arterial Hypertension" by Henkes (1954) is a distinct intrusion into the domain of general medicine.

So far as this country is concerned electro-retinography was first started with the grants of the Indian Council of Medical Research at the Mahatma Gandhi Memorial Medical College, Indore, in the year 1952. The first electro-retinogram in India was recorded on 17-9-1952. Studies at this electro-retinography unit were initially started on normal Indian adults and children and later interesting results of the study on cases of eye manifestations of vitamin-A deficiency were for the first time reported in ophthalmic literature - Dhanda (1955). This talk will be limited only to the results of investigations of normals and vitamin-A deficiency cases.


  Principles of Electro-Retinography Top


We know very well the nature of physical, chemical and electrical changes that take place in different tissues of the retina when stimulated by light.

From the clinical standpoint, these elements are together called the composite retinal activity which in the end will depend on the efficiency of these component factors. A human electro-retinogram is therefore at present considered a com­posite response of the functioning capacity of the retina as a whole.

Attempts have been made with the help of micro-electrodes to study activity of the different layers of the retina and to determine the origin of the electrical potential in the animals. Views have been expressed that on the basis of electro­-retinographic studies of animals two types of retina exist in nature (1) rod dominated Mammalian retina called the E-Retina and (2) pure cone retina of cold­blooded animals called the I retina. Human retina is an E retina.

Animal experiments have also proved that the outer layers of the retina are electrically positive as compared to the inner layers. The positive outer layers are in direct contact with the sclera which continues forward as the cornea while the negative inner nerve fibre layer continues as the optic nerve which is in intimate contact with bones at the optic foramen and therefore continuous with the bones of the temple and forehead.

In the human experiments therefore cornea is treated as the positive pole and the forehead or the temples as the negative pole.

What is required thus is to connect the positive cornea and the negative forehead to an amplifier which should record the differential action potential between the two poles when the retina is suddenly stimulated by a flash of light. The amount of the current recorded by the amplifier is thus a precise means of assessing the functioning capacity of the retina. The experiments with different intensities of illumination for different period stimuli have suggested the following as a diagramatic representation of a human electro-retinogram.

This tracing consists of 4 different elements `a', is the initial negative. 'b'. the main positive, `c'- a slow delayed rise and `d', the off effect. All these features are however not easily detected in a routine electro-retinogram e.g. `a' wave is more prominent in photopic eyes (light adapted eyes) and nearly absent in scotopic eyes (dark adapted eyes). Again `c' and `d' get mixed up in the main `b' wave specially in very short stimulus experiments which are adopted in the study of human eyes.

Height of the main `b'-wave alone therefore represents the functioning capacity of the human retina.

Method and the apparatus

I have adopted in general the same method as by the pioneer, Prof. Karpe of Sweden with one exception that the amplifier I have used gives a calibration of 1 cm. = I mV. instead of 2 cm.=1mV. like the one used by Prof. Karpe.

The subject is first dark adapted for five minutes to bring the retina in a state of complete rest. The frontal band with the indifferent electrode is tied round the head. A contact lens with a silver electrode (active) fitted into it, is introduced in the Conjunctival sac and so adjusted that the silver point is on the limbus. The two electrodes are connected to the amplifier. A saline pad under the frontal electrode of the band completes the circuit. [Figure - 2]

The patient is asked to fix his eyes on a very dim red light on the ceiling and a flash stimulus is given with the help of a timer switch.

In my experiments I use 80 Lux illumination measured with a lux meter and give a ¼ second stimulus, the stimulii repeated every 15 seconds. Simultaneous esti­mation of Vitamin-A in plasma has been done by the antimony trichloride method on a photo-electric colorimeter in suitable cases.

An electro-retinogram could be recorded in most of the subjects above the age of 7 years. Below this age however general anesthesia was necessary.


  Clinical Investigations Top


Electroretinography in normal Indians :

Investigations of normal individuals were subdivided into the following age groups : -

Below the age of 7 years, all under general anesthesia.

Children between the age of 7 to 15 Years.

Adult age group from 15 years to 40 years.

Above the age of 40 years.

The 3 tracings [Figure - 3] are the typical electroretinograms of normals of different age groups. A broad based curve of a child of 4 years is typical of an electroretinogram under general anesthesia. This observation is further confirmed in the case, J. L.. 11 years, where ERGs were recorded before, during and after the anesthesia.

The height of `b'-wave representing the electrical response of the retina slightly varies from individual to individual within a certain range e.g. in case of adults, response from 0.25 mV. to 0.35 mV. is treated as a normal ERG. Where the response is less than 0.25 mV. it is called a subnormal response and when it is more than 0.35 mV. it is called a supernormal response. In all these cases however there should be no error of refraction and media and fundii should be normal. [Figure - 4]a and b show typical subnormal and supernormal ERGs of adults. while the tracing in 4c demonstrates the record of the latent period of an electro­retinogram which in this case is .09 seconds.

Electroretinograms of normal individuals were also recorded with varying intensities of illumination and with varying periods of stimuli. The tracings in [Figure - 6],[Figure - 7] indicate a near `all or none phenomena' which electroretinograms follow.

Large number of normal individuals in each group have been studied to standardise the electroretinography in India in relation to figures published from other countries where electroretinography research is being carried on. The ave­rage `b'-potential of Indian adults in this series has been found to be 0.32 mV. as compared to 0.35 mV. reported by Prof. Karpe from Sweden. [Table - 1] gives the average figures of normal Indian individuals in different age groups:-

A subnormal ERG and distinctly lower Vitamin-A content in normal children is an interesting observation and would explain the sensitivity to and increased frequency of night blindness in children.


  Electroretinography in Vitamin-A Deficiency Top


ERG in Xerosis

Only those cases of xerosis were taken which had characteristic Bitot's spots and there was no other pathology in the conjunctiva to account for the condition. The duration of xerosis in adults was usually long and the patients came to the hospital, in a large number of cases, for cosmetic reasons only. On the other hand. children with xerosis were mostly in nourished. The following three tracings in [Figure - 8] illustrate the good response from the retina in xerosis without malnutrition.

The average b-potential and the vitamin-A content in cases of Xerosis Without nightblindness [Table - 2] resembles the findings in normals. [Table - 1].

A normal electroretinogram in cases of xerosis alone, i.e. without any visual symptoms, is an interesting finding. The interest is further heightened by a nearly normal content of vitamin-A of the blood, in such cases. This raises a pertinent question whether a primary xerosis in the absence of any other conjunctival pathology is a direct result of vitamin-A deficiency or some other indirect manifes­tation. This mystery is further heightened by poor response of xerotic patches in adults to vitamin-A administration. For example in a 20-year-old person who had typical Bitot's spots for three years and had taken 60 injections of Massive-A (Unichem). the xerosis remained unchanged. His ERG was normal.

In children however, xerosis, if untreated, soon results in night blindness. But so long as it remains xerosis alone, the b-potential remains normal and the vitamin content is also normal as shown in the table above.

The conclusion that can be drawn from these observations and investigations of a large number of cases with xerosis is that xerosis is not a direct manifestation of vitamin-A deficiency but is probably an indirect manifestation. of an inter­mediate factor the deficiency of which upsets the metabolism or utilisation of vitamin-A. The specific nature of this factor however cannot be deducted from these investigations but it certainly opens up a new field of biochemical research of an interesting nature.

I even suggest that deficiency of this intermediary factor affects only the con­junctival and corneal epithelium as also confirmed by the following ERGs of extreme deficiency cases. [Figure - 9]a, b.

ERG in night blindness due to vitamin-A deficiency :­

Night blindness due to vitamin-A deficiency is comparatively less common in the adult age groups. I came across only 11 cases 3½ years when these investigations were being carried on. In children night blindness associated with xerosis was a very common clinical feature.

An Extinguished Electroretinogram recorded in cases of night blindness due to vitamin-A deficiency is being reported for the first time except for a passing reference by Karpe (1951) about his experiments on animals. Of 21 eyes of patients above the age of 15 years, all but 5 were extinguished. Again, of the 41 eyes of children, all but 6 showed a completely extinguished, electroretinogram. Even among those who showed some response, only one had a b-pot of .125 mV., one of .10mV. and all the rest 9 had only a response below .005mV.

The average vitamin-A content in all cases with night blindness in children was below 20.0 i.u./100 cc. plasma. In adults, it was found to be 33.0. The observations regarding vitamin-A estimation are made however with reservation and full realisation of the fact that chemical analysis of plasma for vitamin-A gives very variable results. But the results reported here are considered of value because analysis was done under similar circumstances in all cases in that the blood was collected on a fasting stomach, blood was analysed within three hours of its collection and the chemical method adopted as well as the photoelectric colorimeter used was the same during the whole period of this research work.

The following tracings of two cases very precisely show extinguished electro­retinograms which reappear after treatment with vitamin-A. [Figure - 10]A, B.

The following table clearly establishes the direct relationship between the clinical condition, the biochemical findings and the electroretinogram

These findings conclusively prove that onset of clinical manifestation of night blindness due to vitamin-A deficiency is a deciding factor about its effect on the electroretinogram which gets suddenly extinguished as soon as the vitamin-A content of blood falls to a level that it causes clinical manifestation of night blind­ness. Above this critical level, so long as the person either has no manifestation or has xerosis alone, not only the vitamin-A content of blood is at a respectable level but his electroretinogram also remains unaffected. As soon as vitamin-A level falls below this critical level, he develops night blindness and the ERG gets extinguished.

This critical level or minimum vitamin-A threshold of blood must obviously be extremely low as amply shown by the above table. On the basis of these findings, I submit that this vitamin-A threshold in children is in the neighbourhood of 20 i.u. of vitamin-A per 100 cc. of plasma, and a little higher in persons above the age of 15 years. This is reasonably borne out by the fact that all cases of night blindness in children had vitamin-A content of below 20 i.u. and also by the findings that children with vitamin-A content of 26 to 39 i.u. had no symptoms of deficiency (as per the figures in table I) and their electroretinograms were normal for that age group. I arrived at the same conclusion in another way also. Some children with night blindness had vitamin-A content from 8 to 10 i.u. / 100 cc. plasma and their ERGs were completely extinguished. Treatment with Massive-A, 100,000 units injected intramuscularly every 4th day was started. Electroretino­graphy and vitamin-A estimation was also repeated 48 hours after every injection. It was observed that three things happened simultaneously at a certain stage during treatment. Night blindness disappeared, electroretinogram reappeared, and the vitamin-A content rose to a level of 20 i.u. and above.

It can thus be safely concluded that absolute minimum vitamin-A requirements in human beings must be of a very low order indeed. In adults the vitamin-A remains at a fairly high level, anything from 100 to 200 i.u. and with their very low rate of utilisation, the chances of reaching the critical level are very remote and hence the rareness of the manifestation of night blindness due to vitamin-A deficiency in adults.

In children however, the circumstances are just the opposite. Lower level of vitamin-A in their blood [Table - 1] may be due to a lower intake or more probably due to a bigger demand during the developing sta g es of life. It is thus easy in case of children to reach the critical level after a short illness or a few clays of malnutrition. Children are therefore increasingly sensitive to vitamin-A deficiency and that also explains the greater frequency of night blindness in children due to vitamin-A deficiency.

Incidentally these investigations throw an interesting light on the pathogenesis of night blindness and its association with an extinguished electro-retinogram. The degeneration of the retina as a whole in retinitis pigmentosa resulting in an extinguished electro-retinogram is apparently not difficult to understand. A hypothesis put forward by Riggs (1954) in his paper on electro-retinogram in cases of night blindness due to retinitis pigmentosa or of congenital origin has suggested the existence of "holes in the retina" as the mode of an extinction of electro­retinogram in these cases. Observations set forth in this paper obviously prove that this hypothesis need not necessarily be correct. As is shown by these investi­gations, an electro-retinogram can get completely extinguished even though retina may structurally be normal, and only functionally affected as in cases of vitamin-A deficiency. Structural change in the retina for an electro-retinogram to be ex­tinguished is also disproved by the observation that a retina which has lost its electric response completely may regain it quickly fully with treatment with vitamin-A. This leads to the conclusion that no organic change need necessarily be present for electro-retinogram to be extinguished so that an electro-retinogram represents the functioning capacity of retina rather than the srructural pathology.


  Conclusions Top


Recording of electroretinograms is within easy and practical means now. Certain standards have been established on the basic work in India. A completely extinguished ERG in cases of night blindness due to vitamin-A deficiency has been reported for the first time. Vitamin-A threshold in the neighbourhood of 20 i.u./100 cc. plasma is suggested as critical on the basis of biochemical analysis of the blood of normal Indians and of the patients suffering from clinical manifes­tations of vitamin-A deficiency.

It is suggested that the actual primary xerotic condition of the conjunctiva is the result of the deficiency of some intermediary factor in the metabolism and utilisation of vitamin-A. It is explained that functional defect of retina is enough to lead to an extinguished electrical response and a pathological and structural change is not a necessity. It is proved that an extinguished electroretinogram is a reversible phenomenon.

These electroretinographic studies have thus established a distinct relationship at a certain stage of vitamin-A content of blood. in that a stage has been established when three things happen simultaneously, - patient develops night blindness, blood content of vitamin-A falls to the critical level and simultaneously the ERG gets suddenly extinguished. However, like all other methods of intricate research, electroretinography has also its limitations at this stage of its infancy. It is e.g. not possible to detect subclinical stage of vitamin-A deficiency by ERG.

The field is however wide open. It may for instance be valuable to continue the studies with stimuli of minimal illumination and also with monochromatic light stimuli through colour filters. ERG has however established itself as a precise means of diagnostic and prognostic evaluation in conditions like retinitis pigmentosa, siderosis bulbi and detachment retina. It may even be of distinct prognostic utility in systemic vascular hypertension a study of which is under progress at this ERG unit. Thus with so much interest in the subject all over the world, permit me the optimism that it may not be far off when electroretino­graphy becomes as much routine part of medical investigations as electrocardio­graphy and electroencephalography today are.[13]


  Acknowledgment Top


The research in Electroretinography was initiated with the grants of the Indian Council of Medical Research. The Author is grateful to Prof. S. K. Mukherji for allowing free access to the Cardiograph. Thanks are also due to Dr. Sepaha for his valuable help in initiating this work on the cardiograph. Dr. D. P. Mukherji has obliged the Author with the photo­graphs and the slides for the paper and the publications on the subject. Unichem Laboratories of Bombay were very helpful for supplying ample quantities of Vitamin-A for this research work.

 
  References Top

1.
Dhanda. R. P.; (1955); J. Ind. Med. Assoc.: 25; p. 396.  Back to cited text no. 1
    
2.
Dhanda. R. P.; (1955); Archives of Ophth.: 54; p. 841.  Back to cited text no. 2
    
3.
Dhanda. R. P.; (1952-53-54); Tech. Rep. Sc_ Ad. Beard; pp. 251. 229, and 219 res­pectively.  Back to cited text no. 3
    
4.
Holmgren. F. (1865); Upsala Lak. Forh.. 1; pp. 177-91 (quoted in 6.)  Back to cited text no. 4
    
5.
Henkes, H. E. (1954); Archives of Ophth.; 52; p. 221.   Back to cited text no. 5
    
6.
Karpe, G. (1945); Acta Ophth. Suppl. 24; pp. 1-118.  Back to cited text no. 6
    
7.
Karpe, G. and Tansley; (1948); J. Physiol: 107; p. 272.  Back to cited text no. 7
    
8.
Karpe, G. and Vanio Mattilla: (1951); Acia Ophth.; p. 113.  Back to cited text no. 8
    
9.
Linsley, D. B. and Hunter, W. S.: (1939): Proct. Nat. Acad. Sc.; 25.   Back to cited text no. 9
    
10.
Riggs, L. A.; (1954); Am. J. of Ophth.: 38; p. 70.  Back to cited text no. 10
    
11.
Tanslev. K.; (1950); Acta Concill. Ophth. (Br.)   Back to cited text no. 11
    
12.
Zetterstrom, B.; (1951); Acta Ophth. 29; p. 296.  Back to cited text no. 12
    
13.
Zetterstrom. B.: (1952): Acta Ophth. 30; p. 405.   Back to cited text no. 13
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]



 

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