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«CATARACTA BRUNESCENS 531 Since case records indicate that nitroglycerine and other vaso- dilators gave excellent results in the treatment of this ...»

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CATARACTA BRUNESCENS 531

Since case records indicate that nitroglycerine and other vaso-

dilators gave excellent results in the treatment of this condition,

and, since untoward effects were absent, further trials with this

method seem justified5.

BIBLIOGRAPHY

Wilbur, Dwight and Eusterman, G. B.-Nutritional night-blindness. Ji.

1.

Amer. Med. Assoc., Vol. CII, pp. 364-366, February 3, 1934.

May's Manual of the Diseases of the Eye.

2.

Dr. Med. Yozoh Fujihira.-Die atiologische Betrachtung uber die spontane 3.

Nachtblindheit bei den Japanischen Soldaten. Band XII, Heft 6, Juni, 1934, Sonderabdruck aus dem Chiba Igakki, Zasshi.

Jeans, P. C. and Zentmire, Z.-A clinical method for determining moderate 4.

degrees of vitamin A deficiency. Jl. Amer. Med. Assoc., Vol. CII, 12, p. 892, March 24, 1934.

I am indebted to Dr. H. Alexander Brown, M.D., F.A.C.S., San Francisco, for 5.

his helpful co-operation and assistance in these tests; and to Drs.

P. Lazoreve and L. Teile, Leningrad, for their articles on similar research.

CATARACTA BRUNESCENS-STUDY OF THE

NATURE OF THE COLOURING SUBSTANCE

BY PROFESSOR DR{. ELENA PUSCARlu and

DR. JULIUS NITZULESCU

FROM THE OPHTHALMOLOGICAL CLINICS AT JASSY, ROUMANIA

DIRECTOR: PROFESSOR DR. ELENA PUSCARIU

Clinical Considerations CATARACTA Nigra (Wentzel, 1788) or more correctly named Cata- racta Brunescens (Becker, 1881), because in the large majority of cases the lens presents only a more or less deep brown colour, is a rather unusual fornm of cataract. In our practice we have met it only four times among a total of 1,357 cases of cataract.

Some authors believe that it appears especially in myopic eyes, but only one of our four cases was short-sighted. Jess, Rollet Bussy considered that cataracta brunescens has a definitely worse prognosis than an ordinary cataract. They have frequently observed the appearance of iridocyclitis or of infections after the operation, perhaps due to the special predispositon produced by the high myopia. Our cases, just as those of Gifford and others, did not confirm this unfavourable prognosis. All four had a perfectly normal post-operative course.

Our observations can be summarised as follows: Case 1. A peasant, aged 56 years, entered the clinic on October 19, 1925.

The impairment of sight began a year previously in the left eye,

THE BRITISH JOURNAL OF OPHTHALMOLOGY

532 and six months later in the right. There had been no pain or inflammatory phenomena. On admlission R.V.= counts fingers at 1 m. L.V. counts fingers at 060 cms. Skiascopic examination, which was possible in the R.E. only, showed a myopia of 7 D.

The posterior polar cataract permitted the examinationof the fundus, showing peripapillary choroidal atrophy. Intra-ocular pressure in both eyes 18 mm. Blood Wassermann negative. The left eye was operated on November 6, 1925. Extraction with iridectomy and capsulectomy. The lens was deep brown. Postoperative course normal. The sight remained, however, weak due to the numerous foci of choroidal atrophy.

Case 2. S.

R., aged 62 years. Admitted June 28, 1932. The sight began to diminish in 1916. In 1918 she had her left eye operated on in another hospital. At the present time R.V. and L.V. = count fingers at 3-5 metres. The left eye presents a superior coloboma, the lens being subluxated externally in the inferior part.

The pupillary reflex to light persists in the right eye. The light is perceived at 4 5 m. Intra-ocular pressure in both eyes=21 mm.

Blood Wassermann negative. The right eye was operated on July 1, 1932. The lens extracted after iridectomy. Its great mobility made the capsulectomy impossible. We used the cystitome and the lens was extracted with Snellen's loop. It was very flat and deep brown in colour. Post-operative course normal.

Vision, with + 10 D. sph. amounted to 1/8.

Case 3. I.

V., aged 58 years. Entered the clinic on August 6,

1932. R.E. operated on long ago. This eye with a correction of +10 D. sph. had vision of 1/2. Left vision had been diminishing for one year. The lens had become totally opaque. Light perception was still good. Intra-ocular pressure, both eyes=16 mm. Operation on August 19, 1932, with capsulectomy. The lens was brown with greyish peripheral masses. Post-operative course normal. Vision obtained with a correction of +10 D.!= 1/10.

Case 4. N.

M., aged 52 years. Entered the clinic on July 6,

1935. The obscuration of the sight began in 1916, first in the right eye. For one year the patient saw nothing, with this eye and only little with the left. On admission R.V. and L.V.=counts fingers at 20 cms. On slit-lamp examination one saw among the grey striations of the lens a brown colour extending through its whole thickness. Pupillary reflexes normal. Light perception for the right eye at 2-5 m. Intra-ocular pressure R.E. =18 mm., L.E.=21 mm. Blood Wassermann negative. General state good. Blood cholesterol 1'38 per cent. The right eye was operated on October 10, 1935. Extraction of the lens with iridectomy and capsulectomy. The lens was deep brown with thin greyish peripheral layers. The left eve was operated on October 16, 1935.





533

CATARACTA BRIJNESCENS

The lens presented the same aspect. No post-operative inflammation. On October 23 the pupil was occupied by a fine pigmentary net, so that no fundus details could be seen. Vision of the right with + 10 D. correction =counts fingers at 1-5 metres. L.E.=1/10.

In summarising these four cases we note that the age of our patients was not too far advanced (52-62 years).

Our only post-operative complication was a secondary pigmentary cataract, which is generally rare, and has been observed especially in diabetic cataract. We must point out. however, that the vision has remained reduced. This affects somewhat the prognosis of cataracta brunescens, as compared with the usual senile cataract.

Chemical Study Our last case gave us an opportunity of studying the chemistry of the colouring substance in cataracta brunescens. The problem still remains insufficiently elucidated. We find on one side authors who could not succeed in identifying any pigment at all. Mawas, Busacca, Magnasco, Carmli, Cirincione, Neuschuller, Speciale Cirincione believe that the colour is a simple physical phenomenon due to increased refractivity of the lens. The selective absorption of shorter wave-length radiations, should thus be simply determined by the progressive sclerosis of the crystalline fibres. The majority of the authors admit however the existence of a real colouring substance, accumulating slowly in the senescent lens.

Moauro could identify once in some cases pigment of blood origin. Everybody considers to-day that the presence of such pigments is merely accidental, and unrelated to the process which determlines cataracta brunescens. In some of such cases, as happened in our last case, the lens extracted from the eye was stained superficially with a drop of blood. The water in which this lens was immediately washed gave the distinct spectrum of haemoglobin. But no haematic pigment could be identified in the substance of the lens.

The recent publications of Gifford and Puntenny and of Sauermann bring new arguments to confirm the older opinion of Elschnig, Zeinek, Sliussakow, Takeishi, Rollet, Bussy, Burdon Cooper, Gatti, Nicatti, and tend to prove that pigment of cataracta brunescens belongs to the group of melanin.

The chemical composition of melanin is not yet sufficiently known. It seems to represent a group of substances, structurally very closely related. Florence and Enselme characterise melanin as: " Black pigments whose apparition is bound to a transformation in vivo or in vitro of amino-acids principally of tyrosine."

THE BRITISH JOURNAL OF OPHTHALMOLOGY

534 Piettre, through acid hydrolysis, obtained from melanin small amounts of tyrosine, leuicine and other non-crystallisable aminoacids. Alkaline hydrolisis seems to give more alanin. Piettre has found also sulphur and even fatty chains. The action of H202 can determline the producton of small quantities of fatty acids.

Artificial synthetic melanins have been in fact obtained from tyrosine, through the action of special ferments, tyrosinases. Bloch has studied the transformation of a particular synthetic compound, the dioxyphenylalanin (dopa) under the action of a dopaoxydase, present in all places where melanogenesis takes place.

It seems, according to Rapper, that tyrosine or dopa suffer in their transformation into melanin, certain common modifications bringing to the formation of indolic rings. This correlates melanin with another amino-acid, which can result from the autolysis of proteins namely with tryptophane (acid amino-indolpropionic).

In what concerns the eye, the mechanism of production was announced by von Szily in 1911. Gatti thought to explain the brown colour of naphthalenic cataracts through an oxidation of tyrosine. Rollet, Bussy, Corrado and Nicatti have admitted the same origin for the pigment.

The condition for the production of melanin is thus the presence of two elements. A melanogenic substance of protein origin (tyrosine, dopa, perhaps tryptophane) and specific ferment tyrosinase or dopaoxidase. Whenever one of these two factors is present in a tissue we can identify it by adding the second one. The result will then be a production of melanin.

These reactions have been recently applied by Gifford and Puntenny and by Sauermann to the coloured lenses of cataracta brunescens. Gifford and Puntenny could not find any tyrosine in the lenses of cataract (senile, naphthalenic, or brunescens). Sauermann on the contrary found tyrosine and was able to detect also the presence of tryptophane in 65 per cent. of the cataractous lenses.

The dopa method, which brings into evidence the oxidative melanogenic ferments, has given negrative results in the cases of Sauermann and of Waelsh. Gifford and Puntenny have obtained, however, some clearly positive findings. They admit that the brown pigment is produced as a result of a slowly progressing autolysis of the lens proteins. The melanogenic amino-acids produced in the more external layers can diffuse and disappear fronm the lens. Only those resulting in the nuclear layers remain, and under the action of ferments similar to dopaoxydase, are transformed into pigment. Krause questions if the ultra-violet light should have also a role in this transformation of amnino-acids into melanic substances. According to him even other amino-acids, leucin and cystine can produce melanin, whose composition is then so much more variable.

CATARACTA BRUNESCENS 535 According to his own findings Sauermann thinks it is not necessary to admit the intervention of any dopaoxydase. Tryptophane is sufficiently unstable and labile to be transformed into a coloured substance without the action of such a ferment.

Burdon Cooper observes that ratio K/Ca which reaches in a normal lens 380/1 is in a cataracta brunescens 11/1 while in senile cataract only 1/1,5. He questions if K is not an activator of some melanogenic enzyme.

Previous authors studying the actual chemical behaviour of the coloured substance, had reached similar conclusions. Sliusakow thought to identify melanin through spectroscopic analysis, Takeishi through its decolouration by some characteristic bleaching agents (bromine water, chromic acid, K permanganate).

In fact the chemical identification of different pigments found in animal or vegetable bodies is quite difficult. Due to their complex and probably inconstant composition, their properties can hardly offer the possibility of classification. This has been attempted by some authors (Hueck, Vernes).

Our two brown lenses, extracted at a very short interval of days one after the other gave us an opportunity to apply these methods and to trv a chemical identification of the colouring substance.

One of the lenses was ground in a mortar with distilled water and the brown residue, dried, was utilised for some solubility reactions.

The other lens was kept for microscopical analysis and was cut partly fresh or after fixation in formalin, and partly after paraffin embedding.

The following table gives the results of our analysis:

SOLUBILITY

–  –  –

Our results confirm in the first place the existence of a real colouring substance in our lenses. As Schmorl observes, colours due to simple diffraction phenomena in connection with physical structure disappear when this structure is modified. In our case colour remained unmodified by drying, pulverising, treatment with xylol and paraffin embedding. It disappeared on the contrary under the action of the usual melanin bleaching agents, bromine water and K permanganate. But as Gifford points out, the best argument is its solubility in warm (sometimes cold) KOH solutions. We have succeeded in obtaining by means of boiling in 3 per cent. KOH, a yellow solution of the colouring substance.

Such solutions have been obtained by Gifford, Elschnig, Zeinek.

The whole series of reactions leads us to admit that this substance belongs reallv to the group of melanic pigments. In fact, the absence of any colour reaction with concentrated HISO4, the lack of solubility in lipoidic solvents, exclude a carotinoid, chromolipoid nature. TIhe absence of iron excludes the presence of blood pigments (haemosiderin). The bleaching with K permanganate excludes also the possibility of haematoidin.

Absence of malaria, insolubility in strong acid solutions, absence of double refringence plead against the presence of malaria pigment.

On the contrary all the results seem in accord with the properties of melanic pigments, except the non-reduction of AgNO3. Our 537

CATARAcTABRUNESCENS

pigment could not be then a real typical melanin. It could however belong to the so-called lipofuscin or " Abnutzungs pigment."



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