|Year : 1953 | Volume
| Issue : 1 | Page : 15-22
University Eye Clinic Berne, Switzerland
|Date of Web Publication||15-May-2008|
R H Witmer
University Eye Clinic Berne
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Witmer R H. Uveitis. Indian J Ophthalmol 1953;1:15-22
For European ophthalmologists the problem of uveitis is a very important one, for it is one of the most frequent causes of blindness and disability in the western countries. My stay and study in India makes me feel that the incidence of uveitis is by no means less frequent and the danger to vision is as great as in other blinding diseases like glaucoma. trachoma, corneal ulcers and cataract. In India today comparatively less attention is paid to uveitis, but I have noticed its growing importance and interest in places where mass work is giving place to individual attention and treatment. The general health conditions ale not as good in India as they are in our country because the average span of life in your country is 26 years whereas it is 65 years in Switzerland. Perhaps it is not known that even in Switzerland 80-90% of adult people are infected with tubercle during life. On the other hand the death rate of this disease is very low, not even I per thousand. From my observations I feel that the incidence of tuberculosis does not appear to be any less in India and the death rate must be much higher than in our country, I believe it is 10% or even higher. I am therefore convinced that in India uveitis is a more widespread danger than is realised.
I will group my- paper under 3 different heads: - (1) Clinical classification. (2) Diagnosis.(3) Treatment.
| Clinical Classification|| |
I would like to present here the classification by Duke Elder in his book "Recent Advances in Ophthalmology."
(a) Ocular infection :- The eye shares in a general systemic infection as it may happen ill tuberculosis, brucellosis or septicaemia. The ocular inflammation is due to the actual presence of the infecting organisms through the formation of bacterial thrombi in the small vessels. This form of uveitis develops into either an endophthalmitis or a septic choroiditis.
It is significant (1) that the eye is the most common organ to suffer from its effects, and sometimes the only organ to do so and (2) that in a great majority of such infections, no demonstrable bacteraemia is found. Since anatomically no special catchment mechanism is demonstrable in the eye and Rosenow's theory of elective localisation (i.e. various micro-organisms have a predilection for their pet tissues) has been violently repudiated, the only way in which the frequency of such ocular inflammations can be explained is by the theory of sensitization of ocular tissues by repeated leakage of extremely few numbers of organisms of so low a virulence as to succumb to the local immunity, but rendering the eve vulnerable to a later onslaught.
(b) Anaphylactic Uvetis :- This type of uveitis follows an anaphylactic type of reaction from hypersensitivity to foreign proteins. These foreign proteins could he (a) exogenous; (b) endogenous bacterial toxins or (r) endogenous organ-specific proteins e.g. lens and uveal proteins. The reaction manifests itself immediately by (a) congestion: (b) increased capillary permeability causing haemorrhages and exudations and (c) spasmodic contraction of smooth muscle.
(c)Allergic Uvetis :- The sensitization of the eye-ball is affected as stated above in the case of ocular infections, by repeated lodgment of small quantities of organisms of low virulence or a continuous supply of the same front a hidden foots of infection in the body. The uveal inflammation is precipitated by (1) a fresh bacterial thrombus or (2) the toxins of these bacteria.
The characters of this inflammation are peculiar. The inflammation is not immediate but delayed by 24 to 48 hours, and may appear clinically in three fortes -(a) local reaction, at the site of contact (b) a general systemic reaction. and (c) a focal reaction.
The anaphylactic and allergic types of reactions though distinct, may appear together.
A. C. Woods classifies the group of the allergic uveitis into two categories:
1. The granulomatous chronic type. cute to actual invasion of the meal tract by living microorganisms as is the case in tuberculosis, syphilis, brucellosis and streptococcal infections. The features are: an insidious onset, nodular iritis, mutton-fat keratic precipitates, heavy vitreous opacities, choroidal massive exudates. The character of lesions is determined by the local hypersensitivity and immunity excited by the invading organisms themselves, which is best illustrated by the varying degree of tuberculous infection of the eye in children, young adults and older people.
2. The non-granulomatous or serous uveitis, is determined by the allergic response of the tissues, induced by the invading organisms which are killed or subdued by local immunological reaction. Once the hypersensitivity is established a second contact with live or dead bacilli or their products will set up the uveal reaction. The course of this uveitis is acute and the damage usually small. This type is due mainly to rheumatic arthritis, gonococcal, and also tuberculous infection. The clinical features are an acute onset, fine keratic precipitates, fibrinous or gelatinous exudate in the anterior chamber, light vitreous opacities and recovers with surprisingly little damage.
| Diagnosis of Uveitis|| |
As mentioned above, the most common organisms in uveitis are: bacillus tuberculosis, treponema pallidum, brucella, streptococcus and gonococcus.
It is very easy to demonstrate a syphilitic or gouococcal infection by bacteriological and serological tests. In brucellosis too there exist different tests. The difficulty lies much more in the differentiation between strepto- and staphylococcal infections on the one hand and tuberculosis on the other. The average individual in our countries will constantly be exposed to these organisms. The staphylococcal infection of the eye is less frequent and in this case all intracutaneous reaction with a toxin can be made. But most people arc hypersensitive. The determination of sensitivity in streptococcal infectious on the other side is very difficult, due to the multitude of individual strains.
The tuberculous allergy is tested by the Mantoux-reaction. A positive result is very common among - western people. Woods showed that cutaneous sensitivity means high ocular sensitivity; the reverse need not necessarily be so that is, the cutaneous sensitivity may be low in a tuberculous infection of the inner eye.
During the last years. especially since we have got the new antibiotic agents against tuberculosis, paraminosalicylic acid. streptomycin and very recently Rimifon. Roche, we paid much more attention to the diagnosis of tuberculosis. These antibiotics ask for an utmost precision in our diagnosis. The wrong application of PAS, streptomycin and Rimifon might not only be unsuccessful and expensive, but even harmful.
In the following paragraphs I will try to give you an idea of my work during the last few years. This research has not been finished yet and many things are still to be done.
(a) The Haemagglutination Test(Middlebrook-Dubos)
In 1948 Middlebrook and Dubos published in the J. Exp. Med. a very interesting article on a new haemagglutination test for tuberculosis. The test was considered as very specific and what is more important, positive only in active cases of tuberculosis. After many difficulties Dr. Brodhage and myself found a slightly modified method which since has been introduced first in our own clinic and then in other Swiss hospitals. Let me explain in a few words the principle points of this method. It is known that erythrocytes are able to absorb on their surface different substances mainly proteins, for instance antigens. They are then rendered agglutinable by the specific antibody. So sheep red cells can be sensitized with all extract of living tubercle bacilli, as well as with tuberculin, and can then be agglutinated by a serum which contains tuberculous antibodies. I was able to demonstrate that this reaction is specific. The agglutination is inhibited by adding tuberculin or living tubercle bacilli to the serum. I was also able to show the antibody to be a Gamma-globulin by quantitative electrophoretic separation by the method on filter paper described later on. [Figure - 1] shows the electrophoretic curve of a highly positive serum and [Figure - 1]a how the agglutination takes place only in the fraction of the Gamma Globulin.
This agglutination test call also be made with aqueous humour in cases of uveitis, after puncture of the anterior chamber. For this purpose instead of the needle described by Amsler we use a simple needle for injection adjusted on a capillary pipette. In this way the aqueous humour is withdrawn without any pressure or suction, and the injury of the eye is very slight. From only 0.2 cc, of aqueous that call be obtained from the anterior chamber of a human being the agglutination cannot be made in the usual way. I have therefore changed the method in so far as I do not use Kahns-tubes but concave preparation slides, so that one-tenth the amount of fluid will be sufficient. The reading is preferably done with a microscope. [Figure - 2],[Figure - 3], will show you how the agglutination looks like under the microscope.
The results of these haemagglutinations in material over a period of two years may now he stated.
If one compares the Mantoux-reaction to the haemagglutination, one sees generally parallel results, but not in all cases. The patient may be extremely sensitive to tuberculin, but the seroreaction may be negative. In such cases the result of treatment may prove that the ocular disease is not due to tuberculosis, since PAS and streptomycine are unsuccessful and an improvement is only attained by penicillin treatment and removal of focus of infection.
In positive cases on the other hand I found a relation between the degree of the agglutination titer and the influence of specific treatment. Of 38 cases of chronic uveitis those with highly positive serum showed quicker and better improvement on treatment with PAS and streptomycin, while the ones with low titer were little improved by the same treatment.
In all cases of sarcoidosis the sero-reaction was positive. This is a very interesting feature since it proves the tuberculous nature of this disease.
There remains one thing I cannot explain yet. Many cases of acute iritis show a positive haemagglutination. but a thorough general examination revealed no sign of any old extraocular tuberculosis.
Summarizing the results of haemagglutination after Middlebrook and Dubos I may say that this sero-reaction seems to be more precise than the toberculintest. The haemagglutination may tell us something about the immunological conditions, a fact of great prognostic value.
(b) Electrophoresis of Aqueous Humor:
I would like to say some words on the electrophoresis of serum and aqueous humour. The electrophoresis of the human serum is a well known and very precious diagnostic help in internal medicine. The apparatus prepared by Tiselius is very ingenious but very expensive for one simple examination and the average protein content should be between I to 2%,. It is obvious that it will not be possible to determine by this method tile protein content of the aqueous humour which lies in the normal human being between 0.01 to 0.02%. But even in pathological cases, the amount of liquid available by puncture of the anterior chamber is much too small. It is for these reasons that I was very glad, when 1 years ago, 1 was told by a German colleague that a new Method of electrophoresis on filter paper had been invented, so-called microelectrophoresis. I immediately went to Germany, and then constructed for myself the following apparatus. [Figure - 4] shows you the chamber with two troughs containing the platinum-electrodes. The filter paper is then put between these two troughs. filled up with the usual buffered Michaelis-solution (pH 8.6). The material to be examined is laid on one side in a vertical line.
In normal serum one-hundred of 1 c.c. and in uveitis cases an amount of 0.05c.c of aqueous will be sufficient. Under the continuous current of 110 V the different protein fractions are wandering from the negative to the positive pole. The wandering depends upon the molecule size and electrical charge. Albumen. Which has a small size runs quickly while the different globulins of a bigger molecular size travel very slowly. After 12 hours the filter paper is removed and dried at 220 o . The heating denaturates the proteins. Afterwards the paper is stained be a special dye, the Amidoschwarz 10 B Bayer. which gets fixed only on places containing the protein. The superfluous dye is then removed with a mixture of washing of methanol and acetic acid and the final paper shows different lines of a dark blue colour [Figure - 5]. It is then made transparent be paraffin oil and passed through a special colorimeter, which consists mainly of a light source, a diaphragm and a photo-cell, and which measures the extinction. [Figure - 6] shows you the final curve. front which tile relative percentage is calculated by planimetric evaluation.
In concentrated normal aqueous in rabbits I found all the above mentioned proteins. In cases of uveitis in human beings I found curves which correspond more or less to the serum-picture.
I could prove by this method that the proteins in the inflamed aqueous humour are exactly the same as in the serum. The relative percentage of the different fractions does not change in any significant amount, only the total protein content is more or less increased and depends upon the severity of inflammation. It is obvious that if antibodies, for instance anti-tuberculous as mentioned above, can be demonstrated to be present in the aqueous humour. it is more likely that they are coming out of the serum than out of destroyed cells in the anterior chamber.
These are the results of my researches of the last year. Before I finish this paper let me say a few more words on the treatment of uveitis.
| Treatment|| |
Since the year 1948 1 treated a great number of tuberculous eye diseases with PAS and several papers have been published on this subject. First we tried local treatment with an isotonic solution of PAS, only by subconjunctival injections. These injections produce a stiff' high concentration in the anterior chamber. But soon we saw that this topical treatment alone was tenable to improve the uveitis. So we started a general treatment. 12 grammes as a daily dose during 5days combined with subconjunctival injections at intervals of 3 days. Later on we found that subconjunctival streptomycin (in very high dilution of 1mg. in one cc.) combined with general PAStherapeusis had the best effect. Today we give this treatment in every case of tuberculous uveitis, and only very recently we combine this treatment with Rimifon-Roche.
In acute iritis, cortisone. given locally as subconjunctival injections and ointment, has a wonderful effect, but one should not forget, that cortisone is not a causal but only a symptomatic therapeutic agent. If possible it should therefore be combined with specific antibiotic treatment, especially in cases of tuberculosis, in which cortisone may be very dangerous. In chronic granulomatous uveitis cortisone has no effect.
Cases of non-tuberculosis uveitis are treated with Irgapyrine, which seems to be a very good remedy, especially in rheumatic disease. In more chronic cases X-ray in very low dosage of 150 R as a maximum. given in 5-6 doses, often have bench& influence.
I should mention one more detail. In sarcoidosis PAS and Streptomycin do not benefit the disease at all. The best treatment is to send the patient to a sanatorium in the high mountains.
Naturally all cases of uveitis get atropine and hot compresses locally, and all infectious foci are to be removed, when recognized.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]
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