A C T A O P H T H A L M O L O G I C A V O L . 4 8 1 9 7 0

Tennent Institute of Ophthalmology, University of Glasgow, Glasgow, W. 1

(Head of Department - W . S. Foulds)

COLOUR VISION IN TOBACCO AMBLYOPIA

BY

I. A. CHISHOLM, J. BRONTE-STEWART and E. 0. AWDUCHE

One of the diagnostic criteria of tobacco amblyopia is the finding in the centro- caecal area of the field of vision of depressed sensitivity to red and green sti- muli. This is accompanied by a subjective disturbance of colour discrimination. Of the tests available for studying this acquired colour defect, we have found the Farnsworth Munsell Hundred Hue test, although time consuming, most use- ful. This paper reports the results of an investigation by means of this test into the colour vision of patients suffering from treated and untreated tobacco amblyopia.

The Farnsworth Munsell Hundred Hue test (Farnsworth 1943), originally designed for the binocular screening of youthful subjects for congenital colour blindness, consists of a graded series of 85 coloured caps arranged in 4 boxes. The patient is required to arrange the coloured caps into a regular colour se- quence between fixed end caps. He is presented with the coloured caps arranged in a standard random fashion. In the tests carried out by us, no time limit was set for the completion of each box, as many of the patients, in addition to having defective visual acuity, had difficulty in manipulating the caps. The tests were carried out on each eye separately using artificial illumination provided by the Hubble Verivide Cabinet, which satisfies British Standard 950 part I (1967). The patient’s arrangement of the caps is recorded, and from this, his error score can be calculated and expressed numerically or graphically (Fig. 1) .

Colours are perceived and discriminated most accurately between the ages

Received April 6th, 1970.

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13 11 18 17 20 19 % a 14 15 16AH.MaO 21 6 5 4 3 3 4 4 3 3

Fig. 1. Specimen of Farnsworth Munsell 100 Hue score and profile.

of 16 and 35 years (Lakowski 1958). After 55 years there is a rapid deterioration in the ability for fine colour discrimination which affects mainly yellow-blue or violet blue-green discrimination. Red-green discrimination remains fairly stable and is least affected by age. Verriest (1963) demonstrated that in normal healthy subjects the error score for the Farnsworth Munsell Hundred Hue test increased in a positive manner with age, from the age of 35 onwards. At the age of 60 years he quotes a mean error score of 95 with an upper limit of 152 for men.

Untreated Tobacco Amblyopia

A group of 65 patients of mean age 67 years, was composed of 64 males and one female, of whom 57 smoked pipe tobacco only, 3 cigarettes only and 5 both. The mean tobacco consumption of the group was 3.04 ? 1.44 ozs. per week. They were diagnosed as suffering from tobacco amblyopia after the criteria of Heaton et al. (1958). The mean error score for the right eye of all patients for the Farnsworth Munsell Hundred Hue test was 732 + 2 3 6 . In an earlier communi- cation (Chisholm 1969), it was suggested that in the case of error scores above 600, a mean of several test results be taken, and below 600, a single test result would be sufficiently reliable. Where possible, this premise was adhered to. A typical 100 Hue profile in untreated tobacco amblyopia shows depressed dis-

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crimination in most regions of the spectrum (anarchic profile) with preferential loss in the red/green region.

The response of these patients to the pseudo-isochromatic plates of the Ishi- hara pattern (1959) was also examined. The results obtained were not as infor- mative as those obtained by the Farnsworth Munsell Hundred Hue test. All pa- tients showed a gross abnormality of colour vision, some patients being unable to identify the numeral on the first plate, which is recognised by all congenital dichromats.

The best visual acuity (Snellen) of the right eye of all patients prior to treat- ment was converted to percentage visual acuity (Ridley 1959). The mean visual acuity was found to be 18 0’0 (equivalent to 6/36 Snellen) with a range 1.5 O/G-

100 O / o . The near visual acuity was estimated using the notation laid down by the Faculty of Ophthalmologists (Law 1951-52) and similarly transposed to the percentage visual acuity scale. The near acuities lay within the range 8 O/O to 64’0/0 with a mean a t 20.75 0’0 (< N18 a t 15 inches). No significant difference could be demonstrated between the mean distance acuity and near acuity (t = 0.57; n = 116; p > 0.1).

When the Farnsworth Munsell Hundred Hue error score was compared with the distance percentage visual acuity, a significant positive correlation was ob- tained ( = + 0.402; n = 62; p < 0.001). A correlation was also obtained when the Farnsworth Munsell Hundred Hue error score was compared with the pa- tient age ( r = + 0.325; n = 62; p < 0.01). (Fig. 2).

AGE and F.-M. 100 HUE ERROR SCORE in UNTREATED TOBACCO AMBLYOPIA

m .. .. .. 60 ’ . . .

. * . r-0.325 . .

O.O1.prO.OO1

l a , , , . . . . , , . , 3W 500 700 900 1100 I y x )

r.-M.100 Hu. Error Icon

Fig. 2. Correlation of Age and Farnsworth Munsell 100 Hue showing regression line in

untreated tobacco amblyopia.

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In 51 patients a definite estimation could be made of the interval in months between the onset of symptoms and seeking medical advice. When this was compared with the Farnsworth Munsell Hundred Hue error score a positive relationship was found which was just significant (r = + 0.242; n = 49; 0.1 > p > 0.05). Thus, poor colour discrimination tended to be associated with poor visual acuity, increased age, and a long history of visual symptoms. I t was found that patients over the age of 65 years sought medical advice within six months of the onset of symptoms as readily as those patients aged 65 years or younger (xz = 0.11; n = 55; p = 0.95). Thus, age and tobacco amblyopia play separate roles in the production of the acquired dyschromatopsia.

In recent years there has been increasing awareness of the part played by avitaminosis B12 in the aetiology of tobacco amblyopia (Carroll 1956, Heaton et al. 1958, Foulds et al. 1969, a and b). The serum vitamin B12 of these patients was assayed by the Euglena gracilis method after Ross (1952) and a range of concentrations from 15 pg/ml - 572 pg,/ml with a mean at 196 pg/ml was ob- tained. There was no significant relationship between the serum vitamin B12 concentration and the Farnsworth Munsell Hundred Hue error score in our group of cases (r = + 0.161; n = 58; p > 0.1).

Treated Tobacco Amblyopia

Apart from 5, all the patients were given parenteral vitamin BIZ therepy. Initi- ally, they were given either cyanocobalamin or hydroxocobalamin. By ob- serving the improvement in colour vision indicated by a falling 100 Hue error score, it was clear that the hydroxocolabamin form of vitamin BIZ was superior to the cyanocobalamin form, in its therepeutic effect (ChishoZm et al. 1967). All patients therapy was subsequently altered to hydroxiocobalamin at a dose of 1000 pg daily for the first 14 days and then 1000 p g thrice weekly. Adjustments were made, dependent on the response. Patients were advised that it was not necessary to alter their smoking habit.

The improvement in colour discrimination may be observed by studying the change in the Farnsworth Munsell Hundred Hue profile, or alteration in the numerical error score.

A 50 years old male developed classical tobacco amblyopia when smoking 11Jzozs. pipe tobacco per week. H e was treated with hydroxocobalamin and al- lowed to continue smoking. Fig. 3 shows his Hundred Hue profile initially and at 1,3 and 6 months after the commencement of treatment. There has been a no- ticeable shrinkage in the areas of error, a reduction in the error score and a rise in visual acuity.

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Fig. 3. Alteration of Farnsworth Munsell 100 Hue profile with time on treatment with hydro- xocobalamin. Raw scores and visual acuity are shown in untreated state, and after 1, 3

and 6 months therapy.

W e found that when the Farnsworth Munsell Hundred Hue error score was plotted against time on treatment a curve was produced which fitted the expo- nential equation Y = A,-kt + C. When such an equation was converted to lo- garithms a straight line was produced whose slope was given by the value for k. [Log, (Y-C) = Log,A-kt]. Thus, the value for k is an index of the rate of improvement of the patient's colour vision. The value for C is the value at which the exponential curve would become horizontal. It is an individual cha- racteristic, dependent on patient age, and on the presence or absence of any ocular or systemic disease thought to cause an upset in colour discrimination. A computer was used to find the value for C which gave the "best fit" to indivi- dual patient data.

T o illustrate this the following case may be considered. A 68 year old male who smoked 2.5 ozs. pipe tobacco per week developed classical tobacco amblyo- pia. On treatment with hydroxocobalamin he improved. Fig. 4 shows the Farnsworth Munsell Hundred Hue error score for his right eye plotted against time. With a c value of 20, the result of conversion to logarithms is indicated by Fig. 5 .

It is well recognised that patients with tobacco amblyopia show a high inci- dence of complicating systemic disease, particularly of those diseases associated

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Raw 100 Hw S c o n

2 4 6 8 10 I2 14 16 18 20 22 MONTHS

Fig. 4. Raw 100 Hue error score plotted against time on treatment.

1.7-

2.3 -

2.2 -

2.1 -

2.0- 1 I I I 7 1 I I I I 2 4 6 8 10 12 14 16 18 20

MONTHS

2.5 -

2 4 -

2.3 -

2.2 -

2.1 -

2.0- 1 I I I 7 1 I I I I 2 4 6 8 10 12 14 16 18 20

MONTHS

F i g . 5. Data of Figure 4 converted to logarithms. C value of 20 (r = 0.99).

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with deficiency or increased requirement for vitamin BIZ. In our present group the following diseases were found:

Addisonian Pernicious Anaemia 16.90/0 Pre-pernicious anaemia (evidence of pernicious anaemia without anaemia) 16.9 Diabetes 9.3 010

Hepatic disease 3.1 010

Other conditions 6.1 '010

No systemic disease 47.7 '010

From the data the following groups of patients were available for comparing rates of improvement in colour vision, i. e. values of k.

Group Mean value for k

(a) Tobacco amblyopia with no associated disease treated

(b) Tobacco amblyopia with no associated disease treated

(c) Tobacco amblyopia associated with diabetes treated by

(d) Tobacco amblyopia associated with Addisonian per-

(e) Tobacco amblyopia associated with Pre-pernicious

by abstinence from tobacco 0.302

by hydroxocobalamin 0.294

hy droxocobalamin 0.528

nicious anaemia treated by hydroxocobalamin 0.195

anaemia treated by hydroxocobalamin 0.341

When the mean slopes for these groups of patients were compared (Fig. 6) it was found that the rate of recovery in tobacco amblyopia with no associated disease was as rapid if the patient was treated by abstinence from tobacco, as that when treatment with hydroxocobalamin was given and the patient con- tinued to smoke') (t = 0.38, p = > 0.1). The rate of recovery in tobacco am-

Complicated T.A. HYDROXO Img Uncomplicated 1.A

top Y-c

\Pm P A I

l IME(monlh~) TIME(monlh,)

Fig . 6 . Mean rates of improvement in colour discrimination.

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blyopia associated with diabetes was more rapid than when tobacco amblyopia was associated with Addisonian pernicious anaemia'' (t = 2.45; p = 0.05).

The outlook for good visual recovery was as good in tobacco amblyopia un- associated with systemic disease and treated by hydroxocobalamin, as in to- bacco amblyopia associated with diabetes and treated by hydroxocobalamin* (t = 0.80; p = > 0.1). The rate of recovery of colour discrimination was slower in those patients whose tobacco amblyopia was associated with evidence of pernicious anaemia than in any other group. The mean period of treatment with hydroxocobalamin at full dosage of these patients was 20.4 months, before a good standard of vision was achieved. This is prolonged when compared with the mean of 6.82 months of those patients with tobacco amblyopia unassociated with systemic disease. Of the 65 patients, 6 were experiencing a recurrence of the disease, and of these, 3 had pernicious anaemia. I t is possible that these patients had never fully recovered from their previous bout of tobacco am- blyopia which had been treated by abstinence from tobacco. In each of these cases the recurrence had occurred after an interval of not less than 7 years.

(:' Fractional weighted "t" test). W e have found tests of Hue discrimination a more sensitive indicator of

visual improvement than visual acuity and confirm Riddell's (1 936) findings that the return of colour vision takes longer than the central visual acuity. Fig. 7 illustrates the rate of visual improvement and recovery of colour discrimination

400 - %a- t

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of the right eye in a patient suffering from classical tobacco amblyopia treated with hydroxocobalamin. I t is apparent that the visual acuity has returned to normal levels before the ability for colour discrimination. It seems probable that the improvement in colour sense is not wholly dependent on visual acuity.

Discussion

Defective colour vision acquired by patients born with a potentially normal colour vision system develops through various stages, the earliest of which is an abnormal trichromatic stage. Pseudo-isochromatic plates are of little value in detecting this relatively early stage which however, can be picked up by the Farnsworth Munsell Hundred Hue test.

Disease processes affecting the neuro-sensory or conductive layers of the retina will if severe enough lead to blindness. Less severe disease will degrade visual function in a variety of ways including the development of an acquired dyschromatopsia. Thus, lesions of the neuro-sensory retina by and large, result in a loss of colour discrimination in the yellow-blue or violet blue-green and lesions of the conductive layers in the red-green areas of the spectrum respec- tively (Koellner 1912, Cox 1960, Verriest 1963).

Pigment matching tests of which the Farnsworth Munsell Hundred Hue test is a refined and useful example, test the subject’s ability to discriminate between colours which differ only by a small amount when viewed under a constant il- lumination, This test enables a qualitative as well as a quantitative estimation of the colour defect to be carried out (Crone 1961). One of the great merits of the Farnsworth Munsell Hundred Hue test is that elements suitable for de- tecting colour confusion can also be used for detecting the variations in colour discrimination existing among trichromatic observers. To be able to measure these variations the tasks presented for discrimination must involve small colour differences such as are found in the Farnsworth Munsell Hundred Hue test. The differences between successive caps is of the order 2.5 N.B.S. units. The task here may be considered analogous to visual acuity testing. Subjects with acute colour discrimination will arrange the colour series in each box within the two end Iimits correctly, those with lesser discrimination will accu- mulate error scores which are a measure of the degree of displacement from the ideal arrangement (Lakowski 1968).

Galezowski (1883) was first to draw attention to the subjective colour defect of tobacco amblyopia and Groenouw (1892) pointed out that this acquired dyschromatopsia differed from that of the congenital dichromat. COX (1960), Frangois & Verriest (1961), Saraux et al. (1966), Bouniq & Coscas (1966), all record profiles showing defective red-green discrimination in Tobacco Amblyo-

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pia. The Farnsworth Munsell Hundred Hue profiles obtained in our series of cases show a depression of colour discrimination in most regions of the spec- trum but with a predominant red/green loss. W e have noticed also that with treatment the profile improves slowest in the red-green area.

The mode of action of hydroxocobalamin in the treatment of this disease is as yet obscure. The degree of visual improvement with therapy suggests that the neuro-retinal cells have been malfunctioning and on the removal or counter- action of the toxic agent, have undergone recovery. The pallor of the optic disc present initially did not alter on therapy.

The Farnsworth Munsell 100 Hue results are a sensitive index of visual func- tion recovery and allow this to be followed quantitatively. The Farnsworth Munsell 100 Hue profiles do not establish whether tobacco amblyopia is a disease primarily of the optic nerve pathway, or of the neuro-retina as dis- cussed by Schanz (1920) and Phillips et al. (1968). The profiles obtained differ markedly from those obtained from Leber’s Hereditary Optic Atrophy patients in whom the central visual acuity is also poor but the dyschromatopsia is cha- racteristically of a red-green loss.

Summary

A defect of colour discrimination is a consistent feature of tobacco amblyopia. In the untreated condition the defect takes the form of an irregular depression of colour discrimination in most regions of the spectrum. Poor colour discrimi- nation was found to be related directly to poor visual acuity and increased age. Sixty patients were treated with parenteral hydroxocobalamin and continued smoking. Five patients stopped smoking as their only form of therapy. When the disease was associated with pernicious anaemia, the rate of visual improvement was slower than that when diabetes was the associated condition. When there was no associated disease, the rate of visual improvement with hydroxocobala- min was as good as that obtained when smoking was stopped.

Acknowledgement

W e wish to record our thanks to the various Consulting Ophthalmologistsis of the Western Region (Scotland) who referred cases of tobacco amblyopia. W e also thank Professor W. S. Foulds for the use of the facilities of the Tennent Institute, Mr. G. Donald of the Medical Illustration Department, Western Infirmary, for the illustrations, and Mrs. M. Revans for secretarial assistance. Doctor J. F. Adams, Southern General Hospital, carried out the vitamin B12 assays. Professor W. I. Card, Professor of Medi-

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cine in relation to Mathematics and Compating, gave helpful advice on the statistical evaluation of the results. Financial aid for this investigation was provided by the Mc- cine in relation to Mathematics and Computing, gave helpful advice on the statistical dical Research Council and Glaxo Ltd.

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