A Method of Radiation Cataract Analysis and Its Uses in Experimental Fractionation Studies

Abstract

The object of the present study was to devise a method of experimental cataract analysis and to apply it in determining the effect of a fractionation schedule on cataract induction. An experimental analysis of radiation cataract induction requires an investigative procedure which is valid, reproducible, and admits of statistical evaluation. A desirable biological criterion consists of an effect which is observable as to occurrence or measurable as to quantity and preferably can be followed with respect to time. Sufficient numbers of biological subjects should be used to give statistically significant results. The biological criteria in the present work consisted of five defined observational stages of increasingly severe opacity in the rat lens, from no opacity to a completely opaque lens. These classifications were designated 0, 1+, 2+, 3+, and 4+ and were used in the methods of statistical analysis to be discussed below. The time-dose relationship has been studied in many different tissues. In the lens, considered as a tissue, one might expect minimal decrease in effect with fractionation for several reasons. It has a low metabolic activity compared to many other tissues, has no blood supply, and, being enclosed in a capsule, is unable to eliminate injured cells as, for example, is done by desquamation of skin. Cellular and intracellular effects must, however, also be considered. In the clinical study of radiation cataracts reported previously (1), the results indicated a time-dose relationship since the lens seemed able to tolerate higher doses of radiation with increased fractionation. Therefore, in 1959 the present work was started. A preliminary discussion (2) emphasized the ophthalmological aspects and included illustrations of the cataracts, the experimental set-up, and the work sheets. The present work includes the results of lower doses, evaluates results in terms of one classification alone, adds a further analysis of isoeffect curves, and considers the dosimetric and statistical aspects. Many references have been published on the induction of radiation cataract in the mammalian lens since Chalupecky's (3) original work in 1897. Desjardins (4) and Poppe (5) have summarized most of the early literature, especially that concerning patients. There are several experimental reports which indicate a lessened effect on the lens with fractionation (6–12). A summary of more recent papers is given by Merriam and Focht (1). In 1962 Lerman (13) published an extensive bibliography. The induction of radiation cataracts has thus found frequent representation in the literature. It was felt, however, that further experimental studies with large groups of animals under controlled conditions and exposed to varying dosages were necessary to establish with statistical significance a possible time-dose relationship for the mammalian lens. Biological Subjects