Bengt Rosengren

PRESENT THERAPEUTIC RESOURCES IN RETINOBLASTOMA

It is wellknown that retinoblastoma is the next commonest intraocular tumour after the uveal melano-sarcoma. It is a highly malignant tumour, starting in the nuclear layers of the retina. Often it has a multiple origin in one or both eyes. At least 25-300/0 of the cases have tumours in both eyes. Usually the changes are more pronounced in one eye. The tumour strikes young individuals before the age of 4 years, and, as a rule, it is hereditary. The prognosis is pessimistic, if the patient is not treated. The tumour spreads via the optic nerve and the subarachnoidal space to the chiasm and the brain. In later stages there are also distant metastases. Our therapeutic resources in this malignant disease are still strongly limited despite all efforts. In unilateral tumours enucleation must be carried out immediately and is, at present, our only means of therapy. However, with our new therapeutic possibilities this opinion may be changed. The therapeutic difficulties increase considerably in the bilateral cases. The physician, the patient and the relatives are then obliged to decide on extremely difficult problems in view of the bad prognosis. In many of these cases the disease has been regarded as unilateral and one eye has earlier been enucleated. Once the second eye has been affected the vision in the future will quite depend on our possibilities of arresting the tumour growth. Several types of therapy have been tried, aiming to destruct the tumour with as little damage as possible to the eye. Since the beginning of this century X-ray treatment has been used in these special cases. Generally good initial effects are obtained already with moderate dosages. The results have not been of a longstanding nature unfortunately, with recurrences in several cases. Reese et al. (1942) have then increased the X-ray dosages. These authors have compiled a series of about 150 patients, who received a tumour dose of about 6000 r/= 40 days. 5 years later about 500/0 had survived and about 240/0 had cure rate with vision (Reese et al. 1955). The results are surprisingly satisfactory and have not been attained by others. With these large doses, on the other hand, severe complications have

ÜBER DIE BEHANDLUNG DER NETZHAUTABLÖSUNG MITTELST DIATHERMIE UND LUFTINJEKTION IN DEN GLASKÖRPER

Die im letzten Jahrzehnt allgemein verbreitete operative Behandlung der Netzhautablosung hat den Pessimismus, der friiher in bezug auf diesen Krankheitszustand herrschte, zum Verschwinden gebracht. Man hat dabei so bedeutende Resultate erzielt, dass dies operative Verfahren mit Recht als eine der wichtigsten Errungenschaften der Ophthalmologie zu bezeichnen ist. Als Gonin zu Anfang der zwanziger Jahre des Jahrhunderts vereinzelte Falle veroffentlichte, die mittelst der Goninschen Ignipunktur operiert worden waren, enveckte dies nur geringe Aufmerksamkeit. Zu Ende der zwanziger Jahre konnte Gonin jedoch ein umfassendes Material vorlegen, in dem die Anzahl geheilter Falle sich auf nicht weniger als etwa 50 % belief. Andere Operateure erzielten indessen weniger gunstige Resultate, und eine grossere Verbreitung erhielt diese Behandlungsmethode erst, als man sie technisch geandert hatte. Diese dnderung bestand in erster Linie darin, dass man zu einer ausgedehnteren Kauterisation der Bulbuskapsel uberging, was durch Einfuhrung eines neuen Verfahrens, der Koagulation mittelst Diathermie, ermoglicht wurde. Hierdurch erhohten sich die Aussichten auf positive Resultate. Seit dem Jahre 1930 hat nun die operative Behandlung der Netzhautablosung eine immer weitere Verbreitung gefunden, und da nunmehr grosse

TRIALS OF INTRAVITREAL INJECTIONS OF CHEMOTHERAPEUTIC AGENTS IN RABBITS

Clinical trials of local chemotherapy for neoplastic diseases form the background to these animal experiments. As a rule such treatment has been used only when the possibilities of available surgical and radiotherapeutic measures have been exhausted, and on occasions when it is not possible to give further chemotherapeutic treatment either systemically or with extracorporeal circulation. Thus it is usually a question of treating recurrences or metastases, and in several cases a favourable local effect has been reported by infiltration treatment with some chemotherapeutic agents. It is felt however that this method of administration is essentially inferior to perfusion via the blood stream, but for rapidly growing and necrosing tumours where the blood supply is not as good as in normal tissues administration by infiltration may be more effective. For retinoblastoma in one eye the usual practice is to enucleate; if the other eye is affected radiological treatment, either alone or combined with chemotherapy is given. In the first instance there is a choice between external ray treatment from the outside, irradiating the greater part of the globe with conventional x-rays, radioactive cobalt or other high energy rays, and local treatment over a smaller part of the globe using radioactive preparations, formerly radium but now almost exclusively radioactive cobalt. With combined chemotherapeutic and radiological treatment it is usual to give chemotherapy systemically, but recently trials have been carried out injecting the preparation through an arterial catheter in the carotid artery in order to administer it nearer the site of the lesion. The radiotherapy is usually given as external ray treatment.

TWO CASES OF ATROPHY OF THE OPTIC NERVE AFTER PREVIOUS ROENTGEN TREATMENT OF THE CHIASMAL REGION AND THE OPTIC NERVES

Experience, so far, seems to have shown that nervous tissue is very resistant to ionizing irradiation. Consequently, no consideration has been taken to any damage caused by irradiation on the specific nervous tissue with usual therapeutic doses. Recently, however, some observations have been made causing this question to be discussed. Ahlbom (1941) at the Radiumhemmet, thus mentioned damages to the cervical spinal cord in four cases after treatment of cancer in the hypopharynx. The roentgen dose, which struck the cord, was calculated a t 5.000 6.000 r. These damages appeared as cross-section lesions and were only found among very few of the treated cases ( 2 0 / 0 ) . Molin & Sourander (1957) have from the same clinic compiled further diagnosed cases, the total of which was 26. The clinical symptoms started 7-40 months after the irradiation and were manifested particularly as spastic hemiand parapareses. At the section focal necroses could be demonstrated within the part of the spinal cord which had been irradiated. Damages to the chiasmal region have also recently been reported. Forrest et al. (1955, 56) tried, in cases of advanced cancer, to induce destruction of the hypophysis by implantation of radon seeds with a calculated dose of 10.000 to 15.000 r. In four cases of 27 severe damages to the chiasma were observed, which in three cases caused loss of sight of one eye and in one case of both eyes. Damages to the chiasma have furthermore been observed by Buys &. Kerns (1957) after treatment of the hypophysis and the hypothalamus with betatron irradiation in cases of metastasizing cancer. In two out of twelve cases severe visual disturbances occurred leading to blindness. In one case 7.000 r had been

Immobilization of the eye. Evaluation of a new method in retinal detachment surgery.

Experiments on eye phantoms (closed chambers filled with suspensions of lipoid particles in water) have shown that saccadic rotational movements induce liquid currents flowing back and forth through a hole in a latex membrane mounted inside the chamber. It is postulated that rapid (saccadic) eye movements generate similar motions in the liquid vitreous, capable of moving a detached retina.

Indentation of the sclera by means of a silver ball in the surgical treatment of retinal detachment.

The surgical treatment of retinal detachment as devised by Gonin now appears more complicated from the technical point of view than was originally anticipated. It is fundamental to this method that the tear, or at least its approximate position, shall be identified ophthalmoscopically. This is nearly always done, but a few of the failures in treatment are due to lack of achieving this successfully. Further, an exudative process must be provoked at the site of the tear, and this can be effected either by diathermy or by light-coagulation as described by Meyer-Schwickerath. This latter method is now being used in an increasing number of cases with a minimum of damage to the function of the eye. A more difficult problem to solve is how, during healing, to bring the retina in contact with the underlying tissues, pigment epithelium and choroid. Failure to achieve this is by far the predominant cause of negative results. A large number of methods have been developed to fulfil this last demand. By injection of air into the vitreous a pressure is produced from within so that the retina is pressed towards the choroid. It is essential that if this method is to be really effective, the eye shall be in such a position during the first week of healing that the tear lies uppermost, and thereby the air bubble presses against the tear from below. With this method the eye suffers little, but support from the air bubble disappears in about a week on account of its resorption, and healing after this demands care and prolonged bed rest. This method is difficult to practice in those cases where the tear lies below. A similar effect may be achieved by pressure from without, effected in many

SURVIVAL OF HeLa CELLS AFTER LARGE DOSES OF X-RADIATION.

SummaryProlonged incubation revealed that single cells of bottle cultures of HeLa cells may survive even 20 000 r to form colonies of apparently normal cells with unimpaired growth capacity and sensitivity for virus.

ON THE OPERATIVE TREATMENT OF RETINAL DETACHMENT

The operation for retinal detachment by the method of Gonin is based upon the coalescence of the edges of the retinal rupture with the bulb capsule, thus preventing the passage of fluid from the vitreous humour into the retroretinal space. In principle it should be possible to effect a cure in almost cvery case by this procedure, since the granulation necessary for an adhesive retinochoroiditis can always be developed, even in very old and weak patients. A s the proportion of cures has been by no means as great as is to be desired, certain deficiencies must be present in the procedure employed. The purpose of the present communication is to discuss the different phases of the operation in an attempt to determine its weaknesses and the possibilities available for overcoming these. The requirements to be fulfilled by the operation may be summarized as follows :

THE TREATMENT OF RETINOBLASTOMAS WITH A 60CO APPLICATION

For more than six years a special 6OCo applicator has been used as a routine method for the treatment of patients with retinoblastoma. This applicator, which was described by Tengroth (1) and Rosengren and Tengroth (2), is a modification of that originally designed by Stallard (3). The device is in the form of a silver ring which can be sutured circumlimbal to the episclera. Attached to this ring is a malleable arm, the distal end of which is threaded to receive the platinum covered cobalt applicator. The size of the ring as well as the length of the arm can be chosen to fit the individual case (Figs. 1 a and 1 b). The radioactivity which in 1960 measured about 10 mCi has decreased to

SCLERAL INDENTATION BY MEANS OF PLASTIC PLUGS IN THE SURGERY OF RETINAL DETACHMENT

Operative procedure have been available for 30 years as treatment of retinal detachment. The results are, however, still unsatisfactory and it is difficult to evaluate the prognosis. I t is often hard to ascertain the tear especially in cases with cloudy media. Very small holes a re probably not visible and if an exceedingly small hole has been found, it is difficult to exclude the possibility of there being others, which are undiscoverable. Because of these difficulties negative results must be expected in some cases. The first purpose of the operation, which is generally easy to effect, is to produce an exudative reaction at the place of the tear. The technique of diathermy is on the whole standardized even though the cauterization presents certain problems especially concerning the deep effect. The most difficult problem of the operation is to achieve a close contact between retina and choroid during the healing. The evacuation of the subretinal fluid can present a problem in this connection. In certain cases evacuation takes place easily but in other cases it is unsatisfactory, probably due to the fluid being viscous. In order to press retina against choroid over the tear injection of air can be useful. The air bubble must be in contact with the tear during the first days of healing. Because the air bubble is resorbed in rather a short time about 10 days the effect is unsatisfactory in some cases. In the following a new method will be described, which aims at achieving a contact between retina and choroid by indentation of the cauterized scleral area over the tear. In 1937 Jess dealt with the same idea, but the credit of achieving an effective indentation of the sclera by external pressure will be given to Custodis, 1951. In 1953 Schepens utilized the same principle combined with lamellar scleral resection. As the method seems to have certain advantages, especially a shortening of the time of rest in bed, it has been used since September 1954 a t the Eye Clinic of the Sahlgren’s Hospital. An account of the results will be given below.