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Inl. _I. Radiation Oncology Biol. Phys.. Vol. 26, pp. 113-7 14 U.S.A. All ri@s reserved.

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0360.3016/93 $6.00 + .oO 0 1993 Pergamon Press Ltd

0 Editorial

RADIATION-INDUCED

CATARACTS:

SIMPLE

BUT DIFFICULT
FACR

TO QUANTIFY

ROBERT H. SAGERMAN, M.D.,

SUNY Health Science Center, Radiation Oncology, 750 E. Adams Street, Syracuse, NY 132 10 Cateracts, a loss of transparency of the lens, are a feared reaction to irradiation of the eye and orbit, and of nearby structures such as the paranasal sinuses and the pituitary gland. Their development has followed external irradiation, with beams of different linear energy transfer, as well as brachytherapy and total body irradiation. The epithelial cells of the germinative zone, which are the most mitotically active epithelial cells of the lens, appear to be the primary radiation target. Abnormal cells develop, do not differentiate properly and, over a varying period of time, migrate posteriorly and centrally to form a posterior subcapsular cataract, the classical radiation induced lesion. However, a doughnut configuration with a clear center, sectoral clouding, and total opacification may occur. Radiation-induced cataracts may progress or become stationary and may interfere more or less with vision. It is interesting to note that Chalupecky (3), who reported the first experimentally induced radiation cataracts, concluded that the lens was relatively insensitive when it is now known to be exquisitively sensitive but it is more important to know that ophthalmological advances have made radiation cataracts readily amenable to removal with restoration of vision when the rest of the visual pathway is intact (4). Cataract formation is a complex process and its development is affected by trauma, diabetes, hypertension, cigarette smoking, alcohol ingestion, steroids, phenothiazines, chemotherapeutic agents, sunlight, microwave radiation, errors of metabolism, and other intraocular surgery. A radiation dose-response curve is hard to construct because time-dose-fractionation programs and beam quality vary so widely and because much of the available data is from patients in whom the lens was shielded or received scattered radiation. Nevertheless, cataracts developed in some, but not all, patients after a single dose of 2 Gy, fractionated irradiation of 4 Gy over 3 weeks to 3 months, and 5.5 Gy when protraction was greater than 3 months (9). The irradiation technique used is of extreme importance and variations in repetitive field setup makes the Reprint requests to: R. H. Sagennan, M.D., FACR.
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dose to the lens more of a range than a single number. This is the case for retinoblastoma where even a half field beam splitter yields a dose gradient from 90% to 10% over 4 mm (R. H. Sagerman, unpublished data, November 1988). Some of the most accurate lens dose-cataract formation data derives from the work of Schipper et al. who used a meticulous megavoltage technique to deliver 45 Gy/ 15 fractions/3 weeks to 39 children (73 affected eyes) with retinoblastoma ( 12). Cataracts developed in 18 eyes but only when more than 1 mm of the posterior lens was in the treatment field. The chance and the severity of cataract formation were related only to the dose to the germinative epithelium. In one sense, purer data can be gleaned from those patients with an intact globe that is irradiated uniformly because of an orbital tumor. Unfortunately, the radiation dose was sufficiently high (35-65 Gy) that all children with orbital rhabdomyosarcoma treated through an anterior megavoltage field developed cataracts ( 10). If one neglects the underlying process and previous treatment, a similar situation exists for patients conditioned with total body irradiation before bone marrow transplantation. Deeg reported 86 of 277 patients followed for l- 12 years after marrow transplantation developed cataracts (5). Opposing Co6 beams delivered 10 Gy ( 105 patients) in a single fraction or 12 Gy- 15.75 Gy/6-7 days (76 patients); 96 patients received Cytoxan but no irradiation. Cataracts appeared in 80%, 18% and 19% of the 3 groups, respectively, and the relative risk was 4.7 for the single radiation dose group. In this issue of the journal, Kleineidam et al. (6) add valuable data to that which has emanated from the Oncology Unit of the Wills Eye Hospital and from other sources regarding radiation effects in patients treated with brachytherapy, using several radionuclides, for uveal melanoma (1, 4, 7, 8). Only 22% of 365 patients treated with Co6 plaque irradiation, receiving 6-20 Gy at the center of the lens, developed a visually significant cataract attributable to the irradiation within 5 years. Tumor Accepted for publication 19 May 1993.

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1. J. Radiation Oncology 0 Biology 0 Physics

Volume 26, Number 4, 1993

thickness, location of anterior margin relative to the equator and ora serrate, and plaque diameter served as the best covariables for predicting length of time to cataract development. Although the radiation lens dose was not a significant predictive factor in multivariate analysis, it correlated strongly with these factors. In my opinion, this reflects the difficulty researchers have in trying to pin down a single dose when there is a range of doses across the lens, there may be visual damage secondary to the tumor or to the high doses absorbed by the retina/choroid and the definition of what is visually significant in an

elderly population subject to other illness is variable. Although the question of latency is addressed, the cataract rate at 5 years being 22%, 72%, and 81% for low dose (6< 20 Gy), intermediate dose (20-c 40 Gy), and high dose (40> Gy), the incidence rose to 57%, 93%, and 100% for these groups at 10 years. With this information, it is important for the radiation oncologist and ophthalmologist to weigh each patient situation, to choose the most efs fective treatment and to accept cataracts as a complication when unavoidable, recognizing that they can be removed and vision rehabilitated in many patients.

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Augsburger, J. J.; Shields, J. A. Cataract surgery following cobalt-60 plaque. Radiotherapy for posterior uveal malignant melanoma. Ophthalmology 92:815-822;1985. 2. Brooks, H. H.; Meyer, D.; Shields,J. A.; Balas,A. G.; Nelson, L. B.; Fontanesi, J. Removal of radiation-induced cataracts
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treated for retinoblastoma. Arch. Ophthalmol. 108:1701-1708;1990. Chalupecky, H. Uber die Wirkung der Rontgenstrahlen auf das Auge und die Haut. Zbl. Augenheilk 21:234, 267, 368; 1897. Char, D. H.; Lonn, L. I.; Margolis, L. W. Complications of cobalt plaque therapy of choroidal melanomas. Am. J. Ophthalmol. 84:536-540;1977. Deeg, H. J.; Flournoy, N.; Sullivan, K. M.; Sheehan, K.; Buckner, C. D.; Sanders, J. E.; Storb, R.; Witherspoon, R. P.; Thomas, E. D. Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation. Int. J. Radiat. Oncol. Biol. Phys. 10:957964; 1984. Kleineidam, M.; Augsburger, J. J.; Hemandez, C.; Glennon, P.; Brady, L. W. Cataractogenesis after cobalt-60 eye plaque in patients

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radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 26:625630; 1993. Lommatzsch, P. K.; Weise, B.; Ballin, R.; Ein Beitrag zur Optimierung der Bestrahlungszeit bei der Behandlung des malignen Melanoms der Aderhaut mit beta-Applikatoren (106 Ru/l06 Ru) Klin. Mbl. Augenheilk. 189: 133140;1986. Markoe, A. K.; Brady, L. W.; Karlsson, J. L.; Shields, J. A.; Augsburger, J. J. Eye. In: Pered, C., Brady, L., eds. Principles and practice of radiation oncology. 2nd ed. Philadelphia: JB Lippincott; 1992. Merriam, G. R.; Focht, E. T. A clinical study of radiation cataracts and the relationship to dose. Am. J. Roentgenol. 77:759;1957. Sagerman, R. H.; Tretter, P.; Ellsworth, R. M. The treatment of orbital rhabdomyosarcoma in children with primary radiation therapy. Am. J. Roentgenol. Radium Ther. Nucl. Med. 114:31;1972. Schipper, J.; Tan, K. E. P. W.; van Peperzeel, M. A. Treatment of retinoblastoma by precision megavoltage radiation therapy. Radiother. Oncol. 3: 117- 132; 1985.