Indian Journal of Ophthalmology

: 1969  |  Volume : 17  |  Issue : 4  |  Page : 125--138

Ocular toxoplasmosis

SR Malik1, DK Gupta1, OM Phakash2,  
1 Department of Ophthalmology, Maulana Azad Medical College, New Delhi, India
2 Department of Microbiology, All-India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
S R Malik
Department of Ophthalmology, Maulana Azad Medical College, New Delhi

How to cite this article:
Malik S R, Gupta D K, Phakash O M. Ocular toxoplasmosis.Indian J Ophthalmol 1969;17:125-138

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Malik S R, Gupta D K, Phakash O M. Ocular toxoplasmosis. Indian J Ophthalmol [serial online] 1969 [cited 2022 Dec 5 ];17:125-138
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Opinions regarding the etiology of uveitis have been varying from time to time but in most of the cases the diagnosis is of a presumptive nature. The changing view of the etiology of uveitis is reflected in the two reports from the Wilmer Institute, Baltimore, Woods, [69] one in 1941 in which tuber­culosis was rated at 80 per cent in the etiological classification with no place for toxoplasmosis, the other in 1960 in ,vhich tuberculosis is downgraded to 20 per cent, whereas toxoplasmosis and histoplasmosis feature at 36 per cent and 13 per cent respectively. According to the reports from all over the world toxoplasmosis is gaining ground in Western countries, as the most common cause of uveitis especi­ally of chorio-retinitis.

The diagnosis of toxoplasmosis is based on (1) Clinical picture and (2) laboratory investigations i.e. (a) sero­logical tests for toxoplasmosis Sabin and Feldman's [61] dye test, (b) hemag­glutination test of Jacobs and Lunde [29] (c) complement fixation test of War­ren and Sabin [68] , (d) toxoplasmin skin test, and (e) isolation of the parasite. Testing of serum antibodies by the dye test and hemagglutination (H.A.) test are the most useful laboratory aids in the diagnosis of toxoplasmo­sis. Isolation of the parasite is the surest method of demonstrating infec­tion but it is quite difficult in cases of uveitis.

In India the work on the serologi­cal test for ocular toxoplasmosis has been done by only two workers on very few cases, that is by Rawal, Jhala and Patel, [53] who studied only 7 cases of chorioretinitis in which they obtained 100 per cent positive results with dye test and Santok Singh, [64] could find only one case of congeni­tal healed toxoplasmic chorio-retini­tis, which was proved serologically and clinically and one case of a prov­ed carrier. Incidentally Santok Singh was the first ever to report toxoplas­mosis in India.

The present study was undertaken to find out the incidence of toxoplas­mosis causing uveitis on a larger scale.

 Methods and Material

The clinical material on which this work is based comprises cases refer­red for investigation to the Uveitis Clinic of Irwin Hospital, New Delhi.

On the arrival of the patient, a full ophthalmological and medical history was taken including any particular occupational risks, history of fits and any history of contact with pet ani­mals. The following investigations were done in all the 258 cases of uveitis:­

1. Blood examination for hemo­globin, total and differential leuco­cytic count, sedimentation rate and Brucella agglutination.

2. Urine and stool examination.

3. Skiagram of the chest, parana­sal sinuses, sacro-iliac joints and other regions when required. Skiagrams of the skull were taken in children un­der the age of 15 years and in adults who had suspected toxoplasmic lesions in the eye.

4. The skin test for histoplasmosis and the Mantoux test.

5. Investigations for toxoplas­mosis.

i) Toxoplasmin skin test: Toxo­plasmin skin test was done in 137 non-uveitis cases and 258 uveitis cases. It was done by injecting 0.1 cc of toxoplasmin intradermally in the right forearm with a control solu­tion (0.1 cc) in the left fore-arm. Both the antigen and the control were supplied by Eli Lilly & Co., Indianapolis, U.S.A. The readings were taken after 48 hours and were graded as follows:­ [Table 14]

ii) The dye test was clone by the method of Sabin and Feldman [61] with modification of Jacobs (Personal com­munication). The dye test was done in 88 uveitis patients and 44 non­uveitis eases.

iii) The hemagglutination test was done by the methods of Jacobs and Lunde with modification of Jacobs (personal communication). This test was done in 77 uveitis cases.

iv) Isolation of toxoplasma was carried out in the microbiology labo­ratory of the All India Institute of Medical Sciences, New Delhi.


Our cases have been classified into cases of anterior, posterior and gene­ralised uveitis and the different tests for toxoplasmosis have been applied for the purpose of diagnosis. It may be stated that the choice of cases has been an unselected one and not of those with suspected toxoplasmosis as with a typical macular lesion, his­tory of fits and typical appearance in a skigram of the skull, the object being to carry out a field study to fish out the maximum number of cases of toxoplasmosis, includ­ing careers from all uveitis cases, with one or the other laboratory test and then confirm the cause by a cli­nical examination, thereby evaluating the value of each of the tests.

The tests as applied and their re­stilts are tabulated in [Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6] and are compared with each other in [Table 7],[Table 8],[Table 9] and in [Figure 4],[Figure 5]. The tables are all self-expla­natory.

Isolation of the toxoplasma : We could isolate toxoplasma from the lymph-node of a patient of acute ac­quired central retinitis in the right eve [Figure 1] and an old healed patch of chorio-retinitis in the para-macular area with macular stippling in the left eye [Figure 2]. This, to the best of our knowledge is the first serologi­cally and parasitologically proved case of toxoplasmosis from this coun­try. One cervical lymph-node was completely taken out, macerated in sterile physiological saline and in­jected intra-peritoneally into white mice and transfers were continued in mice. On the 13th transfer we were able to locate free toxoplasmas in the mouse peritoneal exudate, [Figure 3] Malik, Gupta, Prakash and Cherian [11] .


The etiological diagnosis of uveitis is difficult and varies from country to country and from person to per­son: The changing trend in label­ling of etiology of uveitis has al­ready been commented upon in the introduction. Many workers have re­ported incidence of toxoplasmosis in uveitis cases varying from 0.5 per cent to 26 per cent (Bennett, [5] Alvaro, [1] Brockliurst, Schepens and Okamura, [7] Bergaust and Rheins [6] .

We investigated 258 cases of uvei­tis in which the following three tests for toxoplasmosis were done in order to find out the incidence of toxoplas­mosis in cases of uveitis.

1. Toxoplasmin Skin Test: Out of the toxoplasmin skin test done in 137 non-uveitis individuals, 5.8 per cent showed positive skin test [Table 1]. The incidence of positive skin test in normal people varies with different workers and can be seen in the last column of [Table 2], which also shows the degree of concordance with the results of other studies on the skin test.

The incidence of positive skin test increased with age up to 50 years after which it started fading. Only one out of 7 cases below 10 years showed positive skin test [Table 3], which has also been found by Schneider, Gaddard and Heinz. [63] This does not correspond with the work either of Frenkel [19] or Feldman and Sabin [11] who found highest positive incidence of 40 - 49 per cent in age groups of 50 - 81 years. However, the skin test was found positive by the same authors in 5 per cent in the 5 - 9 age group, by Fisher [12] 4.3 per cent in children and by Hedquist [22] in only one out of 39 children under the age of 9 years.

In this series out of 108 cases of posterior uveitis (one + reaction was also included amongst positive skin test) 23 patients (21.4 per cent) of pos­terior uveitis showed positive skin test to toxoplasmin which agrees with that obtained by Keller and Vivell [33] . The different incidences of positive skin test obtained in posterior uveitis cases by various workers can be com­pared in [Table 2].

The differences may be due to the fact that all workers may not attri­bute equal significance to a one + re­action. In our control series of non-­uveitis cases, 8 out of 137 were posi­tive but all weakly (one +) positive. It considerably alters our own figures in the case of posterior uveitis from 21.4 per cent to 7.4 per cent if we consider one + as of no significance.

2. Sabin and Feldman's methylene blue dye test:

Muhlpfordt [47] and Awad and Lain­son [2] suggested that sarcocystis and trichomonas vaginalis infection may give false positive results, but Cathie [8] was unable to substantiate these find­ings and concluded that as far as human subjects were concerned the dye test is very reliable. Cathie's work was closely related to the works of many other workers, Eichenwald„ [10] Hogan, [31] Jacobs [27] and Kessel [34] with the result that the dye test now stands on a firm footing.

22 out of 25 positive dye test cases showed the titer in the range of 1:16 to 1:64 [Table 5]. Thus our results correlate with the general contention that the dye test titer in uveitis cases is usually not very high (Perkins [51] ).

In a series of 44 normal cases, 7 (15.9 per cent) showed positive toxo­plasma dye test. [Table 4],[Table 5]. Though the study was done in a lesser num­ber of cases, the results obtained agree fairly closely with those of most of the workers [Table 6].

From the predilection of toxoplas­ma for the nervous tissue it would appear unlikely that iris and ciliary body may be affected though they may be susceptible to infection, as the posterior layers of the iris and ciliary body are derived from neural ectoderm (Perkins [52] ). We have not included anterior uveitis cases with the normals as done by some workers because we found that the incidence of positive dye test in anterior uveitis cases (22.5 per cent) was more than in the normal population (15.9 per cent) and one case of granulomatous anterior uveitis in which both the dye test and haemagglutination were positive in a titer of 1:256, made the cases strongly suspicious to toxoplas­mosis.

Out of the 44 cases of anterior uveitis in 8 (22.5 per cent) the dye test was positive and our results clos­ely agreed with the percentages of other workers 22 per cent Hogan, Thygeson and Kimura [36] ; 24 per cent Hogan [24] ; 20 per cent Jacobs, Naquin, Hoover and Woods [30] ; 24 per cent Hogan [24] . But some workers e.g. Schlaegeh [62] 60 per cent and Perkins [51] 63.4 per cent got a higher incidence of dye test antibodies in anterior uveitis cases.

Case No. 60 of acute granuloma toes anterior uveitis which in all pro­bability is of toxoplasmic origin is of special interest. Local examination of the right eye showed a picture of acute granulomatous uveitis. In ad dition there was a nodule on the iris just near the limbus. The nodule was white in colour and raised from the surface of the iris. Vision was 6/24. On ophthalmoscopic exami­nation, the media were found to be hazy and there were a few exudates in the vitreous. Investigations show­ed only a strongly positive (+++) Mantoux test and the skin test for toxoplasmosis was negative. The re­sults of serological test for toxoplas­ma showed a positive dye test in a titer of 1:256, hemaggl utination test in a titer of 1:256 and complement fixation titer of 1:8.

After about 10 months he had a recurrence of acute iridocyclitis. A fresh white nodule just on the side of the previously healed nodule was vi­sible. His hemagglutination test titer mounted upto 1:1024. Anti­toxoplasmic treatment could not be started as the patient was not willing to be admitted and -outdoor;. treat­ment for toxoplasmosis was consider­ed risky.

Out of 41 cases of posterior uveitis in our series, 16 (39.1 per cent) show­ed dye test antibodies at a titer of 1:16 or above as compared to 22.5 per cent of anterior uveitis cases. [Table 4]. The results are compara­ble with those of Keller and Vivell [33] 41. per cent; Hogan et a1 [25] 42 per cent; Woods, Jacob, Woods and Cook [69] 40 per cent; Schlaegel [62] 40 per per cent; Hogan [24] 48 per cent; but many workers report a rather higher incidence [Table 6].

Incidence of positive dye test in our cases increased as the age ad­vanced [Table 3] and was much more in acute cases especially cases of posterior uveitis [Table 4]. The results thus agree with the works of Jacobs [30] et al and Perkins. [51]

[Figure 4] shows the degree of concor­dance of the dye test in 20 cases as carried out at the laboratory of the all-India Institute Medical Sciences and at Dr. Wall's Laboratory, U.S.A.

3. Hemagglutination test: This test was done in 77 patients of uvei­tis [Table 7],[Table 8]. Out of 77 uveitis patients, 10 (13 per cent) gave a positive result in titers of 1:16 and above [Table 8]. The incidence of positive H.A. test increased with age and was more in anterior uveitis cases especially of acute nature [Table 7]. Hence all the results of our H. A. test match considerably those of the dye test.

Park and Neville did the H.A. test in 123 patients and it was positive in 64 (51 per cent) of his cases at a titer of 1:30 or above. Our results as com­pared to those of Park and Neville [50] are less due probably to a lesser inci­dence of toxoplasmosis in this coun­try.

4. Correlation between dye test, H. A. test and skin test.

No correlation is generally present between the intensity of the skin test reaction and the level of antibody as revealed in the dye test. Skin sensi­tivity appears later than the dye test antibodies and apparently may re­main for longer periods although not so long as serum antibodies (Frenkel and Jacobs). [17] The value of both the dye test and the skin test is prin­cipally in furnishing evidence of past infection with toxoplasmosis.

Correlation between negative dye test and negative skin test was found to be 96.8 per cent and between posi­tive dye test and positive skin test 70.8 per cent [Table 9]. There is a good correlation of skin test with dye test in most studies [Table 10], the lowest being 66 per cent (Kessel) [34] .

Negative hemagglutination test correlation was found in 94% and positive hemagglutination test and positive skin test correlation was found in 50 per cent [Table 11].

In 26 uveitis cases both hemagglu­tination and dye tests were done out of which in 20 cases there was a good correlation between the negative re­sults. [Table 12] shows at a glance the degree of correlation in the posi­tive cases, since the cases for compa­rison are only 27. Discordance was obtained in 2 (7%%) of cases only, in which the dye test was weakly posi­tive in a dilution of 1:16 or less and the hemagglutination test was nega­tive. Both of these patients had negative toxoplasmin skin test. (also see [Figure 5]).

Good correlation between the dye test and hemagglutinatiou test has been found by many workers Lunde and Jacobs [39] 87%; Knierim, Nied­mann and Thierman [35] 86%; Lewis and Kessel [36] 97%; Reus 93%; Lunde, Jacobs and Wood [40] , 98 per cent and Oniki [48] 93%.

Mitchell and Green [46] did not find good correspondence between H.A. and dye test in a series of 73 sera. However, we feel that the H.A. test promises to be a good substitute for the more tiring and painstaking dye test. This test may be made even simpler if the use of formalized ery­throcytes (Lunde and Jacobs [39] , Park [49] , Maloney and Kaufman [42] ) can be adop­ted routinely without presenting ad­ditional problems.

Our result of positive dye test and H.A. test shows the maximum per­centage of positive dye test and H.A. test in juxta-papillary (40 and 50`% respectively) and central chorioditis (42.7% and 18.7%). This finding is in correlation with the works of Gomperts [20] , Garin [18] and many others.

However, in our study a slightly higher positive incidence is also ob­tained in disseminated chorioditis cases (37.8% in dye test and 14.2% in H.A. test), but most of these cases had central involvement also. Per­kins [52] believes that disseminated cho­roiditis cases are unlikely to be due to toxoplasmosis. This study was not done on a very large scale to give any definite evidence.

Etiological diagnosis of uveitis cases:

Twenty-two (8.5%) cases of uveitis were attributed to toxoplasmosis. [Table 13]. The diagnosis was bas­ed on the following points:­

(a) High degree of positive serologi­cal test for toxoplasmosis.

(b) Postive -toxoplasmin skin test.

(c) Clinical picture, (both local and systemic).

(d) Absence of other causes.

Two cases of anterior uveitis were attributed to be due to toxoplasmosis. One case (Case No. 60) has already been described. The second case was that of an old lady, 52 years old, who had acute granulomatous bila­teral anterior uveitis. H.A. test show­ed a titer of 1:1024, which is quite a significant titer. Dye test titer was 1:16, and toxoplasmin skin test was positive. There was no other cause which could be attributed to this diagnosis.

Eighteen cases of posterior uveitis were attributed to be due to toxo­plasmosis out of which 3 were of congenital toxoplasmosis.

The difference in the incidence of toxoplasmosis is due to the unequal prevalence of toxoplasmosis in diff­erent parts of the world. Our series is the largest in this country regard­ing the incidence of toxoplasmosis. We feel that toxoplasmosis does exist in India and accounts for about 8 - 10% of cases of uveitis especially the posterior variety. This is proved by the isolation of toxoplasma by us and by Agarwal (personal communica­tion). The incidence may be more if the dye test and H.A. test are done on relatively larger number of pati­ents.


258 cases of uveitis were studied in which besides other investigations, the dye test was done in 88 uveitis cases and 44 normal cases; hemab glutination test was done in 77 uveitis cases. Toxoplasmin skin test was done in all 258 uveitis patients and 137 non-uveitis cases.

The results are summarized below:­

a) 21.4% of posterior uveitis cases showed positive toxoplasmin skin test as compared to 5% of anterior uveitis and 5.8% of non-uveitis group.

b) 39.1% posterior uveitis cases showed positive dye test at or above a titer of 1:16 as compared to 22.5% of anterior uveitis and 15.9% of non­uveitis patients.

c) H.A. test was done in 77 patients out of which 13.3% showed positive H.A. test at a titer of 1:16 or above.

d) Incidence of positive dye and and H.A. test was much more in pos­terior uveitis cases.

e) Correlation between dye test and H.A. test results was obtained in 93% of uveitis cases.

f) Positive dye test and positive skin test correlation was obtained in 70.8% of cases while negative dye test and negative skin test correlation was ob­tained in 93.8% of cases.

g) Toxoplasma was isolated from a case of acute acquired central reti­nitis in the right eye and old healed patch of chorio-retinitis in the left eye. One moderately enlarged cer­vical lymph-node was taken out fully and injected after maceration into white mice and toxoplasma were iso­lated on the 13th passage.

The results of our investigations are compared with those of other work­ers.[70]


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