Response of the Normal Eye to High Dose Radiotherapy

Response of the Normal Eye to High Dose Radiotherapy

his excellent review analyzes ophthalmologic complications following high-dose irradiation of the orbit and surrounding structures as a necessary adjunct to the treatment of patients with carcinomas of the head and neck region. It confirms the critical importance of dose-fraction size in the production of radiation complications, especially in nerve tissue.

Analyzing 157 patients treated with irradiation for primary extracranial tumors at the University of Florida, the authors present data showing a steeply rising incidence of severe dry eye and associated complications following radiation doses of 45 to 50 Gy using conventional fractionation with treatment of the entire lacrimal gland apparatus. Interestingly, they describe a lower incidence of this complication at equivalent total doses when twice-daily fractionation (120 cGy per fraction) is used--a phenomenon that also has been described for changes in salivary gland function [1].

The authors also discuss the development of corneal ulceration and symblepharon as a consequence of chronic severe dry-eye syndrome. We have noted, especially in the treatment of orbital and retinal malignancies of childhood that when irradiation of the globe is necessary, treatment with the lids open is advantageous in minimizing these problems. Unless the cornea/conjunctiva itself is at risk, this simple action permits some dose-sparing of the cornea and conjunctiva with enface megavoltage techniques and significantly reduces severe complications [2].

The authors note a paucity of patients in their data set for orbital irradiation in the dose range of 45 to 57 Gy. As this is a critical dose range for the establishment of predictable and accurate dose-response data, it might be of interest to survey institutions across the country for their experience in the treatment of lymphoma occurring at this location, as many radiation therapists treat these patients to total doses in this range. Although pediatric rhadomyosarcoma patients also are treated with irradiation in this dose range, use of concurrent chemotherapy, especially with the known radiation sensitizer, dactinomycin (Cosmegan), makes interpretation of these pediatric data problematic, compared to the adult data presented by the authors [3].

We have been impressed with the importance of retinal vascular hemorrhage as a component of radiation retinopathy as a long-term cause of visual loss. Although, clearing of hemorrhage-affected vitreous will usually occur, at least to some extent, vision loss in the affected eye is common following such an event. In a review of children treated with more than one course of external-beam irradiation for retinoblastoma, effective vision was lost in more than 95%, primarily following retinal hemorrhage, despite the passage of many months to over 1 year between treatment courses. This extremely high rate of complications was no doubt accentuated by the daily radiation fraction size of > 300 cGy used at that time for the treatment of these children [4].

Avoiding Dose Inhomogeneities

In many patients receiving orbital/globe/optic nerve irradiation, treatment plans heavily weight the anterior field with respect to other fields (usually wedged laterals). These plans are often quite inhomogeneous. Despite use of daily radiation fractions of 180 to 200 cGy, dose inhomogeneities can be considerable (up to 20% to 25%) and potentially lead to portions of the retina/globe receiving > 240 cGy/d despite the fact that much of the treatment volume receives 200 cGy/d or less.

Should this be the case, the radiation therapist should either design a more homogeneous plan, if possible, or suitably reduce the prescribed daily fraction size because of the critical impact of dose fraction on orbital and ocular complications. Use of three-dimensional planning and treatment approaches are therefore critical for these patients. and their routine use, when indicated, should lead to a significant reduction in complications. This three-dimensional approach also facilitates follow-up evaluation and analysis using a dose-volume histogram approach, which is essential for in-depth understanding of a variety of radiation therapy complications.

The critical importance of fraction size in optic nerve tolerance to irradiation cannot be overemphasized. It is now widely accepted that a single 800-cGy fraction of irradiation to the optic nerve or chiasm represents a tolerance dose when stereotactic radiosurgery approaches are being considered. This must be kept in mind when contemplating stereotactic approaches or "boosts" for certain skull base tumors.

Although almost never seen in a group of treated adults, second tumors of the orbit occur with some frequency in children, especially those with genetic abnormalities such as retinoblastoma. Moreover, as these children commonly survive their malignancy, they may be at risk for this complication for many decades. Orbital bony development abnormalities may, of course, also be expected.

Although the sclera appears to be remarkably resistant to irradiation, use of radioactive plaques attached to this structure for the treatment of retinal tumors, particularly choroid melanoma, necessarily deliver very large doses of irradiation to retinal vessels in order to deliver adequate doses to the "apex" of these tumors (due to the inverse-square law). Over time, most patients lose vision, often due to retinal hemorrhage. Proton-beam therapy can potentially obviate this ophthalmologic problem, and use of conventional dose-fraction treatment with newer hospital-based proton-beam units may allow equivalent tumor control while better preserving vision.


Overall, as emphasized in this paper, careful control of radiation fraction size to ocular structures and restriction of treatment volumes (especially to the lacrimal apparatus), when possible, are of greatest importance in achieving an optimal balance between tumor control and functional preservation. Newer techniques of hyperfractionation and three-dimensional treatment planning and innovative radiation delivery approaches, combined with careful attention to restricting lacrimal gland treatment, when possible, will minimize visual complications and maximize functional preservation. As the authors note, although surgical reports do not consider enucleation as a complication of the treatment of these malignancies, visual loss occurs rapidly and totally.


1. Leslie MD, Dische S: The early changes in salivary gland function during and after radiotherapy given for head and neck cancer. Radiother Oncol 30(1):26-32, 1994.

2. Cassady JR: Radiation therapy in pediatric oncology: Rhadomyosarcoma, in Cassady JR (ed): Medical Radiology-Diagnostic Imaging and Radiation Oncology, pp 281-304. Heidleberg, Springer-Verlag, 1994.

3. Dritschilo A, Weichselbaum R, Cassady JR, et al: The role of radiation therapy in the treatment of soft tissue sarcomas of childhood. Cancer 42:1192-1203, 1978.

4. Cassady JR, Sagerman RH, Tretter P: Radiation therapy in retinoblastoma: An analysis of 230 cases. Radiology 93:405-409, 1969.

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