Radiation Cataract Research Articles

Vertebrate Radiobiology: Histopathology and Carcinogenesis

Knowledge of the histopathologic and carcinogenic effects of ionizing radiation has been amplified greatly under the impetus of atomic fission. Recent research has yielded significant contributions on relationships be­ tween dose, dose rate, type of radiation (electromagnetic and particulate) , and biologic effectiveness; on synergistic and antagonistic factors modifying the biologic effectiveness of radiation; on radiation protection ; on the mechanisms of direct and indirect effects resulting in acute and delayed radiation injury, notably hemorrhage, microbic invasion, leukemia, neo­ plasia, and cataract; and on species and strain differences in radiosensitivity. T he older literature is reviewed by Lacassagne (1 , 2, 3) and Warren et al. (4, 5). Bloom (6) describes in detail the histologic studies of the Plutonium Project, and Hempelmann et al. (7, 8) survey radiation effects in man. Relevant references are included in recent reviews by Brues (9) , Cronkite & Brecher (10) , Curtis ( 1 1) , and Patt (12) , and the carcinogenic action of radiations has been discussed in historical perspective by Furth & Lorenz (13) . It i s accepted that particulate irradiation produces essentially the same changes as electromagnetic irradiation: both act ultimately by causing ioniza­ tions and may be compared quantitatively by expressing ionization values in terms of rep and rem [Evans (14)]. In general, adult and resting . cells are radioresistant, while mitotic or metabolically active cells are sensi­ tive: thus, susceptibility to acute injury is a function of cellular replacement or growth. Liability to tumor-induction, on the contrary, is not dependent on mitotic activity alone: e.g., the replacement rate of epithelial cells of the cornea and small intestine is high, yet they do not give rise to tumors. It seems that both direct and indirect mechanisms are at play in determining the magnitude and character of radiation damage, particularly with respect to induction of neoplasia, but knowledge of these mechanisms is still scant.

Effects of beta irradiation on the rabbit lens.

KNOWLEDGE of early radiation-induced changes in the lens epithelium and of their significance for the development of cataractous lesions has advanced greatly in recent years. The high radiosensitivity of the germinative zone of the lens epithelium, particularly of the cell nuclei in this area, has been demonstrated in x-ray studies¹; in other experimental series the slow progression of damage wrought by various forms of ionizing radiation has been followed, from the microscopically visible changes in the chromatin material of the nuclei to the ophthalmoscopically distinguishable opacities in the lens. On the basis of this enriched understanding of the pathogenesis of radiation cataract, the present study of the effects of beta particles on the lens was undertaken. Although ophthalmologists who have used and recommended beta-ray therapy for various diseases of the eye²have been aware of the danger to the lens when the doses of radiation have had to

Experimental production of radiation cataracts by fast neutrons.

THE PRACTICAL problem of the accidental, and at times unavoidable, exposure of personnel to fast neutrons during the handling of fissionable material, as well as the possibility of more widespread exposure in time of war, stimulated this study. The objectives of these experiments were to determine the fast-neutron dose in dogs which after a single exposure would result in the development of lenticular cataracts and to determine whether a small neutron dose repeated at frequent intervals had a greater or less tendency to produce cataracts than a single larger dose. These studies have been in progress for three years, and the following report represents our findings during this preliminary period. <h3>METHODS</h3> Dogs anesthetized with pentobarbital were rigidly positioned with the left eye closest to a directional beam of neutrons derived from a collimated 16 mev external deuteron beam striking a beryllium target 8 ft. (240 cm.) from the cyclotron. The

Focal scleral necrosis; a late sequel of irradiation.

RADIATION therapy about the eye is being employed by an increasing number of practitioners in an expanding category of conditions. It is only to be expected that an increase in the late complications of irradiation will be experienced. Radiation cataract, the commonest late complication, is known to every ophthalmologist. Its clinical and pathological characteristics have received a great deal of attention. In like manner, late skin changes and effects on bone growth are wellknown and easily recognized sequelae. The purpose of this paper is to report a less common late effect of application of radiation to the globe which presents a striking clinical appearance, namely, focal scleral necrosis. So far as could be determined, this sequela has not previously been described. PRESENTATION OF CASES Case 1. —J. G., a white man aged 38, had had a squamous-cell carcinoma of the right lower lid treated 18 years earlier with radium, 400

Lens and vitreous.

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The medical examination of Hiroshima patients with radiation cataracts.

The medical examination of Hiroshima patients with radiation cataracts.

EXPERIMENTAL RADIATION CATARACT

RADIATION cataracts which have occurred in cyclotron workers and in persons exposed to the atomic bombs are said to have been caused, in part at least, by the fast-neutron component of the radiation. 1 It is therefore of considerable practical moment to know the cataractogenic dose of neutrons as exactly as possible under a variety of conditions and to compare the neutron effects on the lens with those on other tissues and with the effects of other forms of radiation. The biologic action of neutrons has been studied in a variety of tissues, ranging from such relatively simple systems as hatching Drosophila eggs and germinating wheat seedlings 2 to carcinoma in human beings. 3 It is generally conceded that neutrons have much the same qualitative effect on tissue as do x-rays and other ionizing radiations, 4 but the effects produced by different amounts of neutron radiation do not necessarily vary

Further efforts to influence x-ray cataract by chemical agents.

LAST YEAR my co-workers and I reported in a preliminary study on the relation of cysteine treatment to x-ray damage of the rabbit's eye which had been exposed locally to a single dose of 1,500 r of penetrating x-rays. There was at this time strongly suggestive evidence that among the signs of radiation damage to the eye two characteristic late effects of such radiation, epilation and x-ray cataract, were partially prevented by the intravenous use of 2 gm. of cysteine prior to irradiation. These animals have been followed now over periods of 12 to 16 months. Total cataract has developed in the control group in 12 of 14 animals within the observation time of 14 months. None of the cysteine-pretreated eyes showed at this time a lenticular opacity which was dense enough or extensive enough to interfere substantially with the visibility of fundus details. However, all these lenses exhibited some

CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF RADIATION CATARACT

RECENT interest in the effects of radiation on the eye in general and in the production of radiation cataract in particular makes it timely to inquire what the characteristic findings are in this type of cataract and how pathognomonic they are for radiation. Accordingly, the clinical findings have been reviewed in 20 early cases of radiation cataract which we have seen, and the histologic changes have been studied in cross sections from 27 cases¹of radiation cataract, representing various stages of cataract formation. <h3>CLINICAL MANIFESTATIONS</h3> The material comprising the clinical study consisted of 7 cases of cataract following exposure to x-rays or gamma-rays, 2 cases of cyclotron-induced cataract, 10 cases of cataract attributed to the ionizing radiations of the atomic bomb in Japan, and 1 case of cataract resulting from an atomic explosion in this country. The findings were remarkably uniform in all cases. On ophthalmoscopic examination the initial

Induction of Cataracts in Mice by Slow Neutrons and X-rays.

Summary and conclusionsThe lens of the mouse is extremely sensitive to the induction of opacities by both X-rays and slow neutrons. As small a dose as 32 r of total body X-rays causes a slight increase in the per cent of mice developing opacities of the lens. With larger doses the cataract induction rate approaches 100%, the lesions are more severe, and the latency period is shorter. The morphological features of the radiation and senile cataracts of mice are described. The cataracts develop in the immature part of the lens (cortex), while the more mature part of it (nucleus) is spared. Slow neutrons are, on basis of LD-50, at least twice as effective in inducing cataracts as X-rays.

EXPERIMENTAL RADIATION CATARACTS

Radiation cataracts have been of interest as medical and biologic phenomena since the early days of roentgenology, when an unusual type of cataract developed in certain x-ray technicians without necessarily other manifestations of irradiation developing. This apparent predisposition of the lens has intrigued investigators not only because of its practical importance but also because, on a priori grounds, one would not expect a tissue having the slow rate of growth of the lens to be particularly susceptible to radiation. Recent interest in the subject has been accentuated by the occurrence of radiation cataracts in cyclotron workers 1 and in some of the persons exposed to radiation from the atomic bomb. 2 Accordingly, the Committee on Radiation Cataracts was formed under the auspices of the National Research Council for the purpose of stimulating research in this field, and the work to be reported in this paper was supported by a grant

Lens and vitreous.

WITHIN the last year many reports have appeared evidencing noteworthy progress in the investigations of the fundamental problems of the composition and metabolism of the lens and vitreous humor. Efforts were made to solve the problems of the etiology, prophylaxis and treatment of retrolental fibroplasia. The addition of hyaluronidase to procaine solution and the use of curare constituted important advances in the technic of anesthesia for cataract surgery. Publications have appeared on the use of "physiologic glue" for closure of corneal sections. Because of the mounting tension between the Western Nations and those of the Soviet bloc, effects of atomic energy radiations are assuming an ever increasing importance, and concurrently reports of clinical and experimental investigations of various types of radiation cataract have appeared. <h3>CHEMISTRY AND METABOLISM</h3><h3>Respiration.</h3> —Merriam and Kinsey¹have made a valuable contribution to a more intensive study of lens metabolism by developing an apparatus for

Cyclotron-induced radiation cataracts.

Cyclotron-induced radiation cataracts.

OCCUPATIONAL KERATITIDES AND CORNEAL DYSTROPHIES

The definition of a subacute or chronic occupational disease as distinguished from an acute industrial injury due to a single accident has been considerably broadened by legislatures. One therefore has to consider other occupational diseases of the eyes in addition to those previously recognized, namely, miners' nystagmus, glassblowers' cataract and other forms of radiation cataract and cataracts due to systemic poisons. The coverage of occupational diseases is extended not only in relation to the systemic poisons which may indirectly affect vision but in relation to certain substances which may affect the eyes directly, namely, dusts, fumes and oily particles. Those agents affecting the eyes directly may be described as giving rise to occupational keratitides and dystrophies. A clinical and medicolegal review of the subject is therefore presented. A satisfactory etiologic classification of corneal diseases free from conflicting pathologic and anatomic-topographic criteria and morphologic terms, is as yet not available to

OPERATIVE TREATMENT OF RADIATION CATARACT

At the Memorial Hospital for the Treatment of Cancer and Allied Diseases, I had the opportunity to examine 112 eyes with radiation cataract and to operate on 25 of these at the Institute of Ophthalmology. Certain conclusions have been reached regarding the operative treatment in these cases, and it is this phase of the subject that will be presented in this paper. The clinical characteristics, the histologic structure and the other aspects of the subject will be given only as they are related to the operative treatment. In this report an effort has been made to include only cataracts that have unmistakably resulted from irradiation. The criteria have been as follows : A sufficiently large dose of radiation reaching the eye, the appearance of cataractous changes after the usual latent period of from two to three years, the location of cataractous changes in a characteristic manner in the posterior subcapsular region