502

Burnet t , S.: A case of obstructed retinal circulation, with a series of pictures showing the changes in the vascular system during its re-establishment and the formation of new vessels in the retina. Ophth. Record. Vol. 8, p. 601, 1899. Centralbl. 23, 454, 1899.

Carl: Gr.-S. Handb. Vol. 7, A, p. 269, 1915. Coats, G.: Visible anastomoses on the papilla after obstruction of

the central artery. The Royal London Ophthalmic Hospital Reports. Vol. 19, part. 1, p. 78, 1913.

Elschnig, A.: Uber Embolie der Arteria centralis retina?. A. f . A. 24, 69, 1892.

Gonin, J . : Retab1issemen.t de la circulation rktinienne par des anas- tomoses Zt la suite d’une obstruction de l’artere centrale. Ann. d’Oc. f f 3 , 167, 1905.

Harms , C.: Arterielle Anastomosenbildung in der Netzhaut. A. f. 0. G.

H o c k : Ein Fall von Embolie der Arteria centralis retinae. Wien. med. Presse. No. 44, 1869.

Holden, W.: On embolism of a branch of the central artery of the retina. A. of 0. Vol. 12, 1893.

Jensen, V.: Clinical studies of tributary thrombosis in the central retinal vein. Acta ophth. scand. Supplemeritum 10, 1936.

Konigshofer: Anastomosenbildung zwischen zwei Netzhautarterien bei einem Fall von Embolie der Arteria ckntralis retinae. Ophth. Klinik. Vol. 3. p. 133, 1899.

Nettleship, E.: Unusual appearance in case of retinal embolism about 30 hours after its occurrence. Festschrift zur Feier des 70sten Geburtstages v. Helmholtz, p. 78, 1891.

Rados, A. and F . 1,. Candian: Arterielle Anastomose verschiederier retinaler Gefdssysteme im Verlaufe einer Embolie des Haupt- stammes. K1. M. f. A. 66, 797, 1921.

Renne, H.: To Tilfaclde af Hemiplegia carotica. Ophthalm. Selskabs Forhandlinger, p. 7, 1934.

Story , J . : Anomalous distribution of the retinal arteries. Trans. Ophth. SOC. U. K . Vol. 3, p. 102, 1883.

87, 334, 1914.

K. G. P l o m a n (Stockholm):

HEPARIN TREATMENT OF THROMBOSIS IN CENTRAL VEIN OF RETINA.

Heparin is a substance that prevents the coagulation of the blood. It was discovered in 1916 by Howell, and in 1933

503

Charles and Scott of Toronto elaborated a practical method by which it could be procured. Jorpes having demonstrated, in 1935, that its chemical structure is that of a mucoitin poly- sulphuric acid, it became possible to produce it in a pure state. According to investigations carried out by Jorpes, Holmgren and Wilander, heparin is formed in the Ehrlich mast cells. The normal and pathological occurence of these cells in the eye is of great importance in Ophthalmology and therefore. Doctor Anna Stenback of the Ophthalmological Department at the Sabbatsberg Hospital is partaking in a work on this topic. The investigation is based on the fact that heparin forms a reddish violet compound with toluidine blue, as does chon- druitinsulphuric acid.

In 1937 the Toronto scientists Murray, Jacques, Perret, and Best experimented with animals and demonstrated that heparin counteracts the formation of thrombi in the blood, and in the same year Crafoord of Stockholm published an ac- count of his experiments with a view to preventing postopera- tive thrombosis by means of intravenous injections of heparin. In March this year Holmin and the writer reported in the Lancet the first case of thrombosis treated with heparin.

The case was that of a 52 year old nurse suffering from partial thrombosis in the main trunk of the central vein of retina. Upon Holmin’s suggestion she was treated with heparin and recovered rapidly and completely. In view of the fact that thrombosis in the main trunk of the central vein of retina is a disease the prognosis of which is generally bad and always uncertain and by which we have not hitherto had any rational treatment, in addition to its frequency being comparatively limited, we immediately published the case in order that the treatment might be more extensively tested within a reason- able time.

In the same number of the Lancet in which our case was described, Magnusson reported, from Maria Hospital in Stock- holm, a case of thrombosis in the posterior inferior cerebellar artery, a so called Wallenberg syndrome, which treated with heparin was cured. It is known to me that Bostrom has studied a case of thrombosis in the central vein of retina, successfully

treated with heparin, which case is being published in the Lancet.

Seeing that the treatment of thrombosis with heparin has attracted a certain attention I have considered it my duty to give an account of my further experience of this therapy.

First a few words on the treatment itself. Our preparation is a 5 per cent. heparin solution from Apoteksvarucentralen Vitrum in Stockholm, intended for intravenous injections. The solution should be injected with a fine needle and when the latter is removed and thence for a little while the spot where the injection was mdde should be subjected to pressure to prevent the blood, now non-coagulating, from transuding under the skin.

Our case published in the Lancet received during 11 days of her hospital stay first 1, later 1.66 mg/kg body weight, i.e. 60-100 mg. of heparin, every fourth hour, thus a daily dose of maximum 400 mg. Having consulted Jorpes and Crafoord, I have given my later hospital cases 4 injections daily, the first three being 50 mg. each, the last 100 mg., thus a daily dose of 250 mg. As I found that the patients’ general condition was in no way affected by the treatment and that the blood picture remained unchanged, I started treating out-patients. I was then compelled to limit the number of injections to 2 a day, but instead increased the individual dose to 100 or 150 mg. In the beginning the treatment was concluded already after 5 days, later it was continued for 8 to 10 days. I dare not claim that this period is ideal, but the limited time is simply due to financial reasons, heparin being very expensive. 5 c.c., containing 250 mg. of heparin, costs Sw. Kr. 16. Using a daily dose of 300 mg. for 10 days the expense for one single patient is Sw. Kr. 190. I believe that I have so far used heparin for a total of about Sw. Kr. 1500. The management of the hospital has been very understanding, and I cannot but express my gratitude for their assistance.

I have to date treated in all two cases of thrombosis in the trunk and 6 cases in the branches. I have made no selec- tion but have only treated the cases received as out-patients. I have also used heparin in one additional case of thrombosis in the trunk, whose recovery, however, I cannot attribute to

505

this treatment, and in one case of fresh retinal haemorrhage and in one of haemorrhage in the vitreous body on arterio- sclerotic basis.

Table I shows that in case I the vision increased with striking rapidity, the changes in the fundus simultaneousli disappearing. Certainly this was quite a fresh, incomplete thrombosis with limited stasis, but I have never previously observed so favourable a course of this disease. On the other hand I have a few times observed how an originally incomplete thrombosis has within the course of a few days increased by stratification, resulting in complete thrombosis, this being ophthalmoscopically observable in the shape of increased stasis phenomena in and around papilla and in increased haemor- rhages, the vision simultaneously decreasing.

From the beginning case 2 presented a far more serious picture than case 1 - pronounced stasis phenomena in and around papilla with wide, sinuous veins; narrow, barely visible arteries, and numerous though not very profuse hae- morrhages throughout the fundus far out into the periphery. The improvement in vision was slower, but that is no reliable measure of the condition. In macula there still remain oedema and small white exudate spots, whereas papilla is already seen to be well delimited with the arteries quite visible. The hae- morrhages in the remainder of the fundus are to a great extent resorbed. Only three weeks have elapsed since the treatment was started and I believe that this case too has a good prog- nosis even though it may be some time before the central vision improves. In both these cases the tension was quite normal all the time.

The cases of branch thrombosis have been arranged in the table I according to the duration of the symptoms before treat- ment. Even though this must be considered an important de- tail, the general condition of the patient’s vessels and the in- tensity of the circulatory disturbance are still more important, but these latter factors are difficult to grade and tabulate. .

It will be seen that 5 of the cases, Nos. 3, 4, 5, 6, and 8, improved in a fairly short time. In case 3, however, the im- provement changed for the worse three weeks after the treat- ment was started, this due to renewed thrombosis mainly in

50F

2

2 Vll -

0 - 2 0 ‘d VII

C .* v) .*

I 4 h . ? 6 0 V

I v) h

V

0 0 ‘d

O N x & 0 2 0

0 ‘d

0 0 N

0 0 *

0 x 0 2 0 %

~-

0 0 m

0 0 ‘d

0 0 N

0 x 0 0 ‘d

0 0

0 0 0 m

0 0 w

0 0 N

o E x z 0 2 2

v)

2 v1 h

Q m

v) h

V m

‘d W

507

w o

2 VII

d

0

All

2

. .-

0

R 0 R

0 2 2 0

R 9 0 0 m

::z All

0 In

N

0 2 2 0 4 g o O d R o ' 3 N

2 0 -? 0

0 In 0 I n z N

0 In N

0 3 R o 3 2 0 In

N

0 g 2

o r l x o ::

N

0 0 m

d

g o VII

~~

3 : :: N

0 2 VII

3 3 n

0 In

N :: N

3 N

R g 3 - G O

0 4 g o

4 k N

3 n z

4 n

i 34 Acra Ophthalrnologica. Vol. 16. Fac. 4

508

the nasal superior branch; the first thrombus affected the temporal superior branch. Renewed heparin treatment gave no result. Cases 4 and 6 require no comments.

Case 5, so far treated for one week only, presented a strik- ingly rapid increase in vision. The ophthalmoscope already discloses a thinning of the haemorrhages. In case 8 the treat- ment was discontinued already after 5 days owing to the fact that upon the resorption of the haemorrhages in macula there was observed a probably old pigmentation. Case 7 is the only one found to be completely refractory. Owing to maculae corneae before the thrombosis this patient had vision 0.3. It is of course possible that her vision may increase in future, but her macula lutea is still oedematous and shows minor ha em o rrh ages.

I desire to emphasize that it is generally impossible to study the resorption of the haemorrhages from day to day, this rather being done from week to week. However, even when the patient is subjected to heparin treatment the final disappear- ance of the haemorrhages evidently takes quite some time. But it must be considered of value if the changes in and around macula can be improved with reasonable rapidity.

My observations hitherto may be summarized as follows. One case of trunk thrombosis completely recovered within a very short time, a second case objectively showed rapid im- provement. 5 of the 6 cases of branch thrombosis rapidly presented a favourable improvement of vision, case 3 in a fortnight from 0.3 to 0.7, case 4 in 8 days from.0.4 to 0.6, case 5 in one day from 0.1 to 0.7, case 6 in a fortnight from finger count at 2 m. to 0.3, case 8 in a fortnight from 0.1 to 0.3. The average age of these 5 patients is 58 years and the mean improvement of vision is 0.3. Finally one case was not affected by the treatment.

For the sake of comparison I may give my experiences of cases of vein thrombosis in my private practice treated in the ordinary way with iodide of potassium, resting, etc, Out of a total of about 80 cases I have been able to follow 13 cases of trunk and 26 of branch thrombosis for a sufficient time to venture upon conclusions as to results. 9 of the 13 cases of trunk thrombosis went to blindness, 8 due to increased

509

tension, 1 due to retinitis proliferans with ablatio retinae. Of the 4 remaining cases 1 had a final vision of 0.3, 2 of 0.1, and 1 of hand movements.

To make the comparison with the cases treated with heparin fairer I have considered the vision of the 26 cases of branch thrombosis after 3 months; only in two of the im- proved cases have I limited the time of observation to 1 and 2% months, resp. 4 cases with an average age of 65 years have grown worse without any initial improvement, 12 cases with an average age of 62 have remained unchanged during the ob- servation covering 3 months, and 10 with an average age of 58 have improved. 3 cases improved within a fortnight, the others not until after the lapse of one month or more. The average improvement was 0.2. I must add that 3 months is of course too short a time after which to make a conclusive statement as regards a case of branch thrombosis. Improvements can still be seen after 6 and 12 months. But I hope that also the cases treated with heparin may further improve after so long a period.

Parenthetically I desire to mention a circumstance that really has no direct bearing upon the matter. During the last few years 1 have seen several cases of trunk thrombosis during final course of which glaucoma has appeared also in the so- called healthy eye. This may be purely accidental but I have felt compelled always to measure the vision in both eyes in

such cases, My conception is that in an eye with a disposition for glaucoma the thrombosis may very easily cause an increase in tension.

In passing I would now like to show table 11. Case J. B. B. can hardly have been very much affected by the three heparin injections. Apparently we are here concerned with an origin- ally mild case. I must emphasize, however, that although the vision is 1 two and a half months after the disease appearing, the fundus of the eye still presents extensive changes. The other two cases I find difficult to judge. Of course it is not entirely out of question that the heparin may have had a f avourabl e influence.

34'

510

Table 11.

200

0.7

300

0.4

200

Fc 2

Age & Sex

200

300

0.7

200

5 0.

J.B.B. 66 Male Trunk thrombosis

300

200

A. L. B. 5 5 Female Retinal Haemorrhage

300

200 0. H. 71 Male Haemorrhage in vitreous body

- ___ SYmP- toms

bservec for -

, week:

-- 5 days

5 days

Time of observation, days - dose, mg/day - vision -

3

200

0.6

300

5 0.1

- 200

Comments

Treated for 6 weeks with iodide of po- tassium De- creased from well over 0.8 to 0.7, there- fore heparin

After 7 weeks v 1.0

The first day the fundus invisible. Af- ter 30 days it was clearly visible :hrough pro- fuse cloudin- t s s in the vitreous body

Certainly w e a s k ourselves how the heparin may affect a vein thrombosis. The coagulation of the blood is retarded and that - to a certain extent - proportionally to the dose. The blood becomes so to say more fluid. It is reasonable to pre- sume that the heparin prevents the addition of new fibrin to a thrombus and maybe also loose blood corpuscles on its surface can be washed away more easily. One important ad- vantage would then be that a partial thrombosis does not become a complete one, another that i f the efferent flow of blood is facilitated the vitality of the tissue is improved and the resorption possibilities increased. - All the patients sub- jected to heparin treatment have declared, no matter whether

51 1

the vision had increased or not, that they have seen more clearly and this is maybe due to a larger supply of blood passing through retina. - But another possibility should be considered, too. The heparin is considered rather rapidly to disappear from the blood vessels but only a slight amount is found in the urine. Seeing that i t is not quickly destroyed, i t is probable that it penetrates through the capillary walls into the tissues. This heparinization of the tissues may in fresh cases perhaps con tribute to keeping the extravasated blood more fluid and more easily resorbable.

In the case of thrombosis in a vein leading to macula the binocular ophthalmoscope discloses that the haemorrhages often stretch slightly past the horizontal middle plane of macula and an oedema practically always runs further across the whole macula and sometimes a distance over on the other side, then with a steep slope running down into the normal retina. I imagine that even a rather slight resorption of this oedema may result in an improvement of vision. Case 5 is maybe a demonstration of this fact.

No matter how we conceive the effect of the heparin, it is apparently advisable that i t be introduced as soon as pos- sible before any too serious change has occurred in retina.

One more point of view should be emphasized. It is well- known that in cases of trunk thrombosis there is a great danger of secondary glaucoma arising and perhaps it may in some cases be decreased or eliminated by the introduction of heparin treatment.

It will be seen that my experience of heparin as a thera- peutic is as yet not very great, even though it is literally dearly bought. It is to be hoped that increased consumption will make possible a decrease in price. The favourable course in the two cases of haemorrhagcs in the retina and the vitreous body is perhaps merely accidental, but it prompts me at least to make additional tests. Though I certainly do not look upon heparin as a kind of panacea for the treatment of thrombosis, I consider that the experiences so far gained advocate continued experiments. Probably the treatment will be introduced at various clinics and only when there exists

512

collected, larger casuistics can the value of the treatment be reliably estimated.

Friday, 1st of July.

K. 0. G r a n s t r o m (Stockholm):

DIE DAKRYOZYSTITIS BE1 KINDERN, MIT BESONDERER BERUCKSICHTIGUNG VERNACHLASSIGTER FALLE VON

KONGENITALER STENOSE DES DUCTUS NASOLACRIMALIS.

Bei Sauglingen findet man ziemlich oft eine Dakryozystitis, die durch ein angeborenes Hindernis im Ductus nasolacrimalis (D. n.) bedingt ist. Das auf einer Entwicklungsstorung be- ruhende Hindernis kann spontan zuriickgehen, oder es wird durch Sondenbehandlung zumeist leicht uberwunden, worauf die Dakryozystitis ausheilt. Diese bekannten Falle, die. im allgemeinen mehr oder weniger friih im ersten Lebensjahre zur Untersuchung und Behandlung kommen, sollen hier nicht besprochen werden. Wir wenden uns statt dessen dem recht seltenen Vorkommen von Dakryozystitis bei Kindern von uber 1 Jahr zu, u. a. .im Hinblick auf die Moglichkeit, dass eine vernachlassigte kongenitale Stenose des D. n. auch hier die Ursache darstellen kann.

Im Schrifttum wird den Dakryozystitiden bei Kindern nach dem Sauglingsalter kein grosses Interesse gewidmet. Tuber- kulose und Lues sollen verhaltnismassig haufige Ursachen sein. Eine kongenitale Stenose des D. n. als Ursache auch bei grosseren Kindern wird hin und wieder envahnt, z.B. Stock, scheint aber wenig beachtet zu sein und ist z. B. in der Mono- graphie von Gilbert sowie in Meisners Darstellung im Kurzen Handbuch uberhaupt nicht erwahnt. Riser hat in einem Ma- terial von 36 Fallen von Affektionen der Tranenwege bei Kindern im Alter von 0-10 Jahren 25 Falle von kongenitaler Stenose des D. n., von denen 21 im ersten Lebensjahre, 3 im