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Visual Results Following Cobalt Plaque Radiotherapy for Posterior Uveal Melanomas
Visual Results Following Cobalt Plaque Radiotherapy
for Posterior Uveal Melanomas
ALAN F. CRUESS, MD,* JAMES J. AUGSBURGER, MD,* JERRY A. SHIELDS, MD,* LARRY A. DONOSO, MD, PhD, * JONATHAN AMSEL, SeDt
Abstract: Visual results of cobalt plaque radiotherapy on the eyes of 77 patients with posterior uveal melanoma in one eye and pretreatment visual acuity of 20/25 or better in both eyes were analyzed using actuarial methods. The study demonstrated that eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years. It also showed that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss than those treated for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy. [Key words: cobalt plaque radiotherapy, posterior uveal melanoma, radiation retinopathy.] Ophthalmology 91:131-136, 1984
Enucleation has long been considered the standard form of therapy for patients with a posterior uveal melanoma. However, Zimmerman and co-workers have recently questioned the advisability of enucleation on the basis of their demonstration of an unexpected increase in tumorrelated metastatic mortality within 2 years after enucleation.I,2 As a result, there has been renewed interest in alternative forms of management, including observation, 3 photocoagulation,4 various forms of tumor resection,5 Cobalt-606 and Iodine-125 plaque radiotherapy,1 and proton beam8 and helium ion irradiation. 9 Since the initial report by R.F. Moore lO regarding the use of radioactive plaques in the treatment of choroidal From the Oncology Service' and the Department of Epidemiology,t Division of Research, Wills Eye Hospital, Thomas Jefferson University, Philadelphia. Presented at the annual meeting of the American Academy of Ophthalmology, San Francisco, Califomia, October 3D-November 5, 1982. Supported in part by the Retina Research and Development Foundation, the Ocular Oncology Research Fund, Wills Eye Hospital, the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Inc., and the Ministry of Health of Ontario. Reprint requests to James Augsburger, MD, Oncology Service, Wills Eye Hospital, Ninth and Walnut Streets, Philadelphia, PA 19107.
melanomas, several authors have reported favorable results using cobalt plaques. I1,12 However, since these reports, radiotherapy has been widely criticized because of the radiation retinopathy and resultant visual loss that occurs in some eyes treated with this technique. 13-15 To determine more accurately the rates of visual loss among our patients treated with cobalt plaque radiotherapy, we analyzed follow-up visual acuities using actuarial table methods.
PATIENTS AND METHODS We reviewed the records of all patients treated by Cobalt-60 plaque radiotherapy for a posterior uveal melanoma between May 1976 and December 1981. We selected those patients who had visual acuity of 20/25 or better in both eyes at the time of treatment as the basis of this study. Clinical methods of evaluation of each tumor included indirect ophthalmoscopy, fundus drawing, contact and/or Hruby lens examination and, where applicable, transconjunctival transillumination. Fundus photography and fluorescein angiography were performed in eyes with clear media, and ocular ultrasonography, using A and B scan, was performed in every case. Cobalt plaque 131
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radiotherapy was carried out uniformly. We attempted to deliver, when possible, a minimum of 8,000 rad to the tumor apex but not more than 45,000 rad to the tumor base. Computer-generated isodose curves indicated the approximate radiation doses within the tumor and at all sites within the eye. The surgical technique of plaque application, including tumor localization, has been previously described. 16 Follow-up studies performed at 3-, 4-, or 6-month intervals included ophthalmoscopy, fundus drawing, Hruby lens, and/or contact lens fundus biomicroscopy, 45 0 and 180+ 0 fundus photography in eyes with clear media, Aand B-scan ultrasonography and in some cases, intravenous fluorescein angiography. In analyzing the records of each patient, the visual acuity and the reason for any decrease in acuity were determined at each follow-up visit. The dimensions, volume and location of each tumor relative to the fovea, optic disc and lens were calculated from the photographs, ultrasonograms and fundus drawings. The dose of radiation received by the fovea, optic disc and lens was determined from the computer-printed isodose curves. Actuarial table techniques 17 were used to study the rates of visual loss for treated eyes as a function of the dose of radiation to the fovea, disc, and lens. Severe visual loss was defined for this study as a reduction of visual acuity to 20/200 or worse. The normal fellow eyes served as controls.
RESULTS Seventy-seven of237 patients treated with cobalt plaque therapy from May 1976 to December 1981 qualified for our study because their pretreatment visual acuities were 20/25 or better in both eyes. All 77 patients were Caucasian. Forty-one were male, 36 were female. Their ages ranged from 25 to 77 years, (mean, 52.5 years). The right eye was affected in 33 patients while the left eye was affected in 44. Sixty patients had a choroidal melanoma while 17 had a ciliochoroidal melanoma. The maximal basal diameter of the 77 tumors ranged from 5 to 22 mm, (mean, 10.8 mm). Thickness of the 77 tumors ranged from 1.5 to 12.4 mm, (mean, 5.6 mm). Cubic volume of the 77 tumors ranged from 62.0 to 3583.6 mm 3, (mean, 667 mm 3). Seven of the 77 tumors were categorized as small (greater than or equal to 5 mm in maximal basal diameter or 2 mm in thickness or both, but less than or equal to 10 mm in maximal basal diameter and 3 mm in thickness). Thirty of the 77 were categorized as medium (larger than small tumors but less than or equal to 15 mm in maximal basal diameter and 5 mm in thickness). Forty of the 77 were categorized as large (greater than 15 mm in maximal basal diameter or 5 mm in thickness or both). The sizes of the 60 choroidal melanomas ranged from 5.0 mm to 17.0 mm (mean, 10.2 mm) maximal basal diameter, from 1.5 mm to 10.1 mm (mean, 4.9 mm) thickness, and from 214 mm 3 to 3584 mm 3 (mean, 1233.2 mm 3) cubic volume. The location of the margin of each 132
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of the 60 choroidal tumors relative to the fovea ranged from the edge of the fovea to 18 mm from the fovea (mean, 6.0 mm), and the location of the margin of each of these tumors relative to the optic disc ranged from 0.75 mm to 18.0 mm from the optic disc (mean, 7.5 mm). The location of the point at the tumor base nearest the center of the lens ranged from 8 mm to 17 mm from the lens (mean, 13.1 mm). Calculated radiation doses to the fovea for the 60 eyes containing a choroidal tumor ranged from 950 rad to 32,000 rad (mean, 6,339 rad). Doses to the optic disc ranged from less than 1,000 rad to 15,000 rad (mean, 4,653 rad), and to the lens from 700 rad to 6,000 rad (mean, 1,867 rad). Six of these 60 eyes (10.0%) experienced severe visual loss during the period of follow-up. Five of these six eyes demonstrated macular nonproliferative radiation retinopathy as the principal mechanism of their visual loss. One of these eyes also developed radiationinduced optic neuropathy and three of them developed a shallow exudative retinal detachment. The sixth eye sustained a vitreous hemorrhage secondary to tumor necrosis. One patient developed a nuclear sclerotic cataract in the treated eye and a similar cataract in her fellow eye during the period of follow-up. She regained visual acuity of20/25 in each eye following bilateral cataract extraction. The radiation doses to the fovea in these six eyes, which experienced severe visual loss, ranged from 2,300 rad to 32,000 rad (mean, 16,071 rad). Doses to the optic disc ranged from 3,500 rad to 12,700 rad (mean, 6,885 rad), and to the lens from 700 rad to 4,800 rad (mean, 1,950 rad). In contrast, for the 53 eyes with a choroidal melanoma which did not experience severe visual loss during the period of follow-up, the radiation doses to the fovea ranged from 950 rad to 29,000 rad (mean, 5003 rad). Doses to the optic disc ranged from 1,100 rad to 15,000 rad (mean, 4,346 rad), and to the lens from 750 rad to 6,000 rad (mean, 1,854 rad). The sizes of the 17 ciliochoroidal melanomas ranged from 7 mm to 22 mm (mean, 13.1 mm) in maximal basal diameter, from 4.2 mm to 12.4 mm (mean, 8.0 mm) in thickness, and from 214.2 mm 3 to 3583.6 mm 3 (mean, 1233.2 mm 3) in cubic volume. In these 17 eyes the location of the point at the tumor base nearest the center of the lens ranged from 8 mm to 10.5 mm from the lens (mean, 9.3 mm). The location of the margin of each of these tumors relative to the fovea ranged from 9 mm to 18 mm (mean, 14.2 mm), and the location of their margins relative to the optic disc ranged from 6 mm to 21 mm (mean, 13.3 mm). Calculated radiation doses to the lens for the 17 ciliochoroidal tumors ranged from 3,150 rad to 17,500 rad (mean, 6,903 rad). Doses to the fovea ranged from 1,140 to 6,500 rad (mean, 2,334 rad) and to the optic disc from 1,000 to 14,000 rad (mean, 3,241 rad). Two of these 17 eyes (11.7%) experienced severe visual loss in the treated eye during the interval of follow-up. The mechanism of visual loss in these two eyes was exudative retinal detachment involving the macula. The lens remained clear in both eyes. The radiation doses to the fovea in the two eyes which experienced severe visual loss ranged from 2,100 rad to 3,000 rad
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(mean, 2,550 rad). Doses to the optic disc ranged from 1,700 rad to 5,300 rad (mean, 3,500 rad), and to the lens from 3,100 rad to 4,500 rad (mean, 3,800 rad). In contrast, the radiation doses to the fovea in the 15 eyes with a ciliochoroidal melanoma which did not experience severe visual loss during the period of follow-up ranged from 1,140 rad to 6,500 rad (mean, 2,816 rad). Doses to the optic disc ranged from 1,000 rad to 14,000 rad (mean, 3,207 rad), and to the lens from 2,300 rad to 8,000 rad (mean, 3,877 rad). Figure 1 presents the actuarial curves of the rates of preservation of visual acuity better than 20/200 and better than 20/50 for the 77 eyes with posterior uveal melanoma managed by cobalt plaque radiotherapy. At the 36-month follow-up point on the graph, 81 % (cumulative actuarial percentage) of the eyes retained visual acuity better than 20/200, but only 62% (cumulative actuarial percentage) retained visual acuity better than 20/50. Figure 2 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 following cobalt plaque radiotherapy for the 40 of these 77 eyes which contained a large posterior uveal melanoma, as well as for the 37 eyes which contained a medium or small posterior uveal melanoma. At the 36-month followup point on the graph, 95% (cumulative actuarial percentage) of the eyes containing a small or medium posterior uveal melanoma retained visual acuity better than 20/200, but only 48% (cumulative actuarial percentage) of those containing a large posterior uveal melanoma retained visual acuity better than 20/200. Figure 3 shows foveal radiation dose and Figure 4 shows the optic disc radiation dose as a function of tumor location relative to the fovea and disc, respectively, for the entire group of77 eyes managed by cobalt plaque therapy. These figures illustrate that treatment of an eye containing a posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations almost invariably resulted in a radiation dose greater than 5000 rad to the fovea and/or disc if the margin of the tumor was located within 5 mm of these structures. Figures 5-
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7 show the relationship between the location of the tumor margin relative to the fovea and the foveal dose of radiation obtained according to whether the tumor was large (Fig 5), medium (Fig 6) or small (Fig 7). These figures illustrate that treatment of an eye containing a large posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations is much more likely to result in a foveal radiation dose greater than 5000 rad than is treatment of a medium or small tumor located the same distance from the fovea. Figure 8 shows radiation dose to the lens as a function of tumor location relative to the lens for the entire group of 77 eyes managed by cobalt plaque therapy. This figure illustrates that treatment of an eye containing a posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations generally results in a radiation dose to the lens greater than 2500 rad if the distance between the point at the tumor base nearest the center of the lens is less than 10 mm. Figure 9 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 for the 133
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56 of the 77 eyes containing a posterior uveal melanoma which received a foveal radiation dose of less than 5,000 rad, as well as for the other 21 eyes which received a foveal radiation dose of more than 5000 rad. At the 36month follow-up point on the graph, 91 % (cumulative actuarial percentage) of the eyes which received less than 5,000 rad to the foveal retained visual acuity better than 20/200, but only 52% (cumulative actuarial percentage) of those which received more than 5,000 rad to the fovea retained visual acuity better than 20/200. Figure 10 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 for the 51 of the 77 eyes containing a posterior uveal melanoma which received a radiation dose of less than 5,000 rad to the optic disc, as well as for the other 26 eyes which received a disc radiation dose of more than 5,000 rad. At the 36-month follow-up point on the graph, 92% (cumulative actuarial percentage) of the eyes which received less than 5,000 rad to the optic disc retained visual acuity better than 20/200, but only 65% (cumulative actuarial percentage) of those which received more than 5,000 rad to the disc retained visual acuity better than 20/200.
Seven additional eyes experienced temporary severe visual loss during the period of follow-up. Six of these eyes developed a serous retinal detachment which extended to involve the fovea, but the subretinal fluid resolved spontaneously with visual recovery in every case. One eye developed a vitreous hemorrhage, which also resolved spontaneously with visual recovery. None of the 77 treated eyes in this series required secondary enucleation because of continued tumor growth or complications of radiation. Two of these patients died of metastatic uveal melanoma. No appreciable change in visual acuity occurred in any of the 77 fellow (control) eyes during the period of follow-up.
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DISCUSSION Although the reports by Stallard II and others 12,16 regarding the use of cobalt plaque radiotherapy for the treatment of posterior uveal melanomas indicate a high rate of local tumor control and systemic cure, several
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recent reports have stressed the frequent need for secondary enucleation and the common occurrence of radiation retinopathyl3-15 with resultant loss of visual acuity. The most comprehensive report to date of visual acuity data following cobalt plaque radiotherapy is MacFaul's follow-up report l8 of 107 patients treated in the Moorfield's Oncology Clinic between 1960 and 1975. Seventyeight of these patients were still living at the time of this follow-up and 51 still retained their eye. MacFaul found 4 of these 51 eyes (8%) had no light perception, 4 (8%) had light perception vision, 10 (20%) perceived hand motions, 13 (25%) had visual acuity between 20/200 and 20/120, and 20 (39%) retained visual acuity between 20/ 60 and 20/20. Of Stallard's first 100 patients treated by cobalt plaque therapy, 23 required secondary enucleation of the treated eye. The 5-year survival rate among these patients was 86%.19 Since these results are not corrected for unequal periods offollow-up by actuarial table meth-
ods, they are not directly comparable to the results of our study. Our study demonstrates that eyes containing medium and large posterior uveal melanomas with margins closer than 5 mm to the fovea and/or optic disc almost invariably receive a radiation dose to these sites of greater than 5,000 rad (Fig 1). Eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years, but the visual prognosis appears to be relatively good for eyes receiving a radiation dose less than 5000 rad to these sites. Our study also shows that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss within the first 3 years of follow-up than are those treated by cobalt plaque radiotherapy for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy. If the trend in visual loss that we have demonstrated during the first three years following cobalt plaque radiotherapy of posterior uveal melanomas continues, more patients will eventually lose a substantial portion of their pretreatment vision.
REFERENCES 1. Zimmerman lE, Mclean IW, Foster WD. Does enucleation of an eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells? Br J Ophthalmol 1978; 62:420-5. 2. Zimmerman lE, Mclean IW. An evaluation of enucleation in the management of uveal melanomas. Am J Ophthalmol1979; 87:74160. 3. Gass JOM. Observation of suspected choroidal and ciliary body melanomas for evidence of growth prior to enucleation. Ophthalmology 1980; 87:523-8. 4. Vogel MH. Treatment of malignant choroidal melanomas with photocoagulation. Evaluation of 1O·year follow-up data. Am J Ophthalmol 1972; 74:1-11.
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5. Peyman GA, Raichand M. Full-thickness eye wall resection of choroidal neoplasms. Ophthalmology 1979; 86:1024-36. 6. Ellsworth RM. Cobalt plaques for melanoma of the choroid. In: Jakobiec FA, Ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 76-9. 7. Packer S, Rotman M. Radiotherapy of choroidal melanoma with iodine125. Ophthalmology 1980; 87:582-90. 8. Gragoudas ES, Goitein M, Verhey L, et al. Proton beam irradiation: an altemative to enucleation for intraocular melanomas. Ophthalmology 1980; 87:571-81. 9. Char DH, Castro JR, Quivey JM, et al. Helium ion charged particle therapy for choroidal melanoma. Ophthalmology 1980; 87:565-70. 10. Moore RF. Choroidal sarcoma treated by intraocular insertion of radon seeds. Br J Ophthalmol 1930; 14:145-52. 11. Stallard HB. Radiotherapy for malignant melanoma of the choroid. Br J Ophthalmol 1966; 50:147-55. 12. Long RS, Galin MA, Rotman M. Conservative treatment of intraocular melanomas. Trans Am Acad Ophthalmol Otolaryngol1971; 75:8493.
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13. MacFaul PA, Bedford MA. Ocular complications after therapeutic irradiation. Br J Ophthalmol 1970; 54:237-47. 14. Bedford MA, Bedotto C, MacFaul PA. Radiation retinopathy after the application of a cobalt plaque; report of three cases. Br J Ophthalmol 1970; 54:505-9. 15. Chat DH, Lonn L1, Margolis LW. Complications of cobalt plaque therapy of choroidal melanomas. Am J Ophthalmol 1977; 84:53641. 16. Shields JA, Augsburger JJ, Brady LW, Day JL. Cobalt plaque therapy of posterior uveal melanomas. Ophthalmology 1982; 89:1201-7. 17. Hillis A. Improving reporting of follow-up data. Am J Ophthalmol1982; 93:250-3. 18. MacFaul PA. Local radiotherapy in the treatment of malignant melanoma of the choroid. Trans Ophthalmol Soc U K 1977; 97:421-7. 19. MacFaul PA, Morgan G. Histopathological changes in malignant melanomas of the choroid after cobalt plaque therapy. Br J Ophthalmol 1977; 61:221-8.
for Posterior Uveal Melanomas
ALAN F. CRUESS, MD,* JAMES J. AUGSBURGER, MD,* JERRY A. SHIELDS, MD,* LARRY A. DONOSO, MD, PhD, * JONATHAN AMSEL, SeDt
Abstract: Visual results of cobalt plaque radiotherapy on the eyes of 77 patients with posterior uveal melanoma in one eye and pretreatment visual acuity of 20/25 or better in both eyes were analyzed using actuarial methods. The study demonstrated that eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years. It also showed that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss than those treated for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy. [Key words: cobalt plaque radiotherapy, posterior uveal melanoma, radiation retinopathy.] Ophthalmology 91:131-136, 1984
Enucleation has long been considered the standard form of therapy for patients with a posterior uveal melanoma. However, Zimmerman and co-workers have recently questioned the advisability of enucleation on the basis of their demonstration of an unexpected increase in tumorrelated metastatic mortality within 2 years after enucleation.I,2 As a result, there has been renewed interest in alternative forms of management, including observation, 3 photocoagulation,4 various forms of tumor resection,5 Cobalt-606 and Iodine-125 plaque radiotherapy,1 and proton beam8 and helium ion irradiation. 9 Since the initial report by R.F. Moore lO regarding the use of radioactive plaques in the treatment of choroidal From the Oncology Service' and the Department of Epidemiology,t Division of Research, Wills Eye Hospital, Thomas Jefferson University, Philadelphia. Presented at the annual meeting of the American Academy of Ophthalmology, San Francisco, Califomia, October 3D-November 5, 1982. Supported in part by the Retina Research and Development Foundation, the Ocular Oncology Research Fund, Wills Eye Hospital, the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Inc., and the Ministry of Health of Ontario. Reprint requests to James Augsburger, MD, Oncology Service, Wills Eye Hospital, Ninth and Walnut Streets, Philadelphia, PA 19107.
melanomas, several authors have reported favorable results using cobalt plaques. I1,12 However, since these reports, radiotherapy has been widely criticized because of the radiation retinopathy and resultant visual loss that occurs in some eyes treated with this technique. 13-15 To determine more accurately the rates of visual loss among our patients treated with cobalt plaque radiotherapy, we analyzed follow-up visual acuities using actuarial table methods.
PATIENTS AND METHODS We reviewed the records of all patients treated by Cobalt-60 plaque radiotherapy for a posterior uveal melanoma between May 1976 and December 1981. We selected those patients who had visual acuity of 20/25 or better in both eyes at the time of treatment as the basis of this study. Clinical methods of evaluation of each tumor included indirect ophthalmoscopy, fundus drawing, contact and/or Hruby lens examination and, where applicable, transconjunctival transillumination. Fundus photography and fluorescein angiography were performed in eyes with clear media, and ocular ultrasonography, using A and B scan, was performed in every case. Cobalt plaque 131
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radiotherapy was carried out uniformly. We attempted to deliver, when possible, a minimum of 8,000 rad to the tumor apex but not more than 45,000 rad to the tumor base. Computer-generated isodose curves indicated the approximate radiation doses within the tumor and at all sites within the eye. The surgical technique of plaque application, including tumor localization, has been previously described. 16 Follow-up studies performed at 3-, 4-, or 6-month intervals included ophthalmoscopy, fundus drawing, Hruby lens, and/or contact lens fundus biomicroscopy, 45 0 and 180+ 0 fundus photography in eyes with clear media, Aand B-scan ultrasonography and in some cases, intravenous fluorescein angiography. In analyzing the records of each patient, the visual acuity and the reason for any decrease in acuity were determined at each follow-up visit. The dimensions, volume and location of each tumor relative to the fovea, optic disc and lens were calculated from the photographs, ultrasonograms and fundus drawings. The dose of radiation received by the fovea, optic disc and lens was determined from the computer-printed isodose curves. Actuarial table techniques 17 were used to study the rates of visual loss for treated eyes as a function of the dose of radiation to the fovea, disc, and lens. Severe visual loss was defined for this study as a reduction of visual acuity to 20/200 or worse. The normal fellow eyes served as controls.
RESULTS Seventy-seven of237 patients treated with cobalt plaque therapy from May 1976 to December 1981 qualified for our study because their pretreatment visual acuities were 20/25 or better in both eyes. All 77 patients were Caucasian. Forty-one were male, 36 were female. Their ages ranged from 25 to 77 years, (mean, 52.5 years). The right eye was affected in 33 patients while the left eye was affected in 44. Sixty patients had a choroidal melanoma while 17 had a ciliochoroidal melanoma. The maximal basal diameter of the 77 tumors ranged from 5 to 22 mm, (mean, 10.8 mm). Thickness of the 77 tumors ranged from 1.5 to 12.4 mm, (mean, 5.6 mm). Cubic volume of the 77 tumors ranged from 62.0 to 3583.6 mm 3, (mean, 667 mm 3). Seven of the 77 tumors were categorized as small (greater than or equal to 5 mm in maximal basal diameter or 2 mm in thickness or both, but less than or equal to 10 mm in maximal basal diameter and 3 mm in thickness). Thirty of the 77 were categorized as medium (larger than small tumors but less than or equal to 15 mm in maximal basal diameter and 5 mm in thickness). Forty of the 77 were categorized as large (greater than 15 mm in maximal basal diameter or 5 mm in thickness or both). The sizes of the 60 choroidal melanomas ranged from 5.0 mm to 17.0 mm (mean, 10.2 mm) maximal basal diameter, from 1.5 mm to 10.1 mm (mean, 4.9 mm) thickness, and from 214 mm 3 to 3584 mm 3 (mean, 1233.2 mm 3) cubic volume. The location of the margin of each 132
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of the 60 choroidal tumors relative to the fovea ranged from the edge of the fovea to 18 mm from the fovea (mean, 6.0 mm), and the location of the margin of each of these tumors relative to the optic disc ranged from 0.75 mm to 18.0 mm from the optic disc (mean, 7.5 mm). The location of the point at the tumor base nearest the center of the lens ranged from 8 mm to 17 mm from the lens (mean, 13.1 mm). Calculated radiation doses to the fovea for the 60 eyes containing a choroidal tumor ranged from 950 rad to 32,000 rad (mean, 6,339 rad). Doses to the optic disc ranged from less than 1,000 rad to 15,000 rad (mean, 4,653 rad), and to the lens from 700 rad to 6,000 rad (mean, 1,867 rad). Six of these 60 eyes (10.0%) experienced severe visual loss during the period of follow-up. Five of these six eyes demonstrated macular nonproliferative radiation retinopathy as the principal mechanism of their visual loss. One of these eyes also developed radiationinduced optic neuropathy and three of them developed a shallow exudative retinal detachment. The sixth eye sustained a vitreous hemorrhage secondary to tumor necrosis. One patient developed a nuclear sclerotic cataract in the treated eye and a similar cataract in her fellow eye during the period of follow-up. She regained visual acuity of20/25 in each eye following bilateral cataract extraction. The radiation doses to the fovea in these six eyes, which experienced severe visual loss, ranged from 2,300 rad to 32,000 rad (mean, 16,071 rad). Doses to the optic disc ranged from 3,500 rad to 12,700 rad (mean, 6,885 rad), and to the lens from 700 rad to 4,800 rad (mean, 1,950 rad). In contrast, for the 53 eyes with a choroidal melanoma which did not experience severe visual loss during the period of follow-up, the radiation doses to the fovea ranged from 950 rad to 29,000 rad (mean, 5003 rad). Doses to the optic disc ranged from 1,100 rad to 15,000 rad (mean, 4,346 rad), and to the lens from 750 rad to 6,000 rad (mean, 1,854 rad). The sizes of the 17 ciliochoroidal melanomas ranged from 7 mm to 22 mm (mean, 13.1 mm) in maximal basal diameter, from 4.2 mm to 12.4 mm (mean, 8.0 mm) in thickness, and from 214.2 mm 3 to 3583.6 mm 3 (mean, 1233.2 mm 3) in cubic volume. In these 17 eyes the location of the point at the tumor base nearest the center of the lens ranged from 8 mm to 10.5 mm from the lens (mean, 9.3 mm). The location of the margin of each of these tumors relative to the fovea ranged from 9 mm to 18 mm (mean, 14.2 mm), and the location of their margins relative to the optic disc ranged from 6 mm to 21 mm (mean, 13.3 mm). Calculated radiation doses to the lens for the 17 ciliochoroidal tumors ranged from 3,150 rad to 17,500 rad (mean, 6,903 rad). Doses to the fovea ranged from 1,140 to 6,500 rad (mean, 2,334 rad) and to the optic disc from 1,000 to 14,000 rad (mean, 3,241 rad). Two of these 17 eyes (11.7%) experienced severe visual loss in the treated eye during the interval of follow-up. The mechanism of visual loss in these two eyes was exudative retinal detachment involving the macula. The lens remained clear in both eyes. The radiation doses to the fovea in the two eyes which experienced severe visual loss ranged from 2,100 rad to 3,000 rad
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(mean, 2,550 rad). Doses to the optic disc ranged from 1,700 rad to 5,300 rad (mean, 3,500 rad), and to the lens from 3,100 rad to 4,500 rad (mean, 3,800 rad). In contrast, the radiation doses to the fovea in the 15 eyes with a ciliochoroidal melanoma which did not experience severe visual loss during the period of follow-up ranged from 1,140 rad to 6,500 rad (mean, 2,816 rad). Doses to the optic disc ranged from 1,000 rad to 14,000 rad (mean, 3,207 rad), and to the lens from 2,300 rad to 8,000 rad (mean, 3,877 rad). Figure 1 presents the actuarial curves of the rates of preservation of visual acuity better than 20/200 and better than 20/50 for the 77 eyes with posterior uveal melanoma managed by cobalt plaque radiotherapy. At the 36-month follow-up point on the graph, 81 % (cumulative actuarial percentage) of the eyes retained visual acuity better than 20/200, but only 62% (cumulative actuarial percentage) retained visual acuity better than 20/50. Figure 2 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 following cobalt plaque radiotherapy for the 40 of these 77 eyes which contained a large posterior uveal melanoma, as well as for the 37 eyes which contained a medium or small posterior uveal melanoma. At the 36-month followup point on the graph, 95% (cumulative actuarial percentage) of the eyes containing a small or medium posterior uveal melanoma retained visual acuity better than 20/200, but only 48% (cumulative actuarial percentage) of those containing a large posterior uveal melanoma retained visual acuity better than 20/200. Figure 3 shows foveal radiation dose and Figure 4 shows the optic disc radiation dose as a function of tumor location relative to the fovea and disc, respectively, for the entire group of77 eyes managed by cobalt plaque therapy. These figures illustrate that treatment of an eye containing a posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations almost invariably resulted in a radiation dose greater than 5000 rad to the fovea and/or disc if the margin of the tumor was located within 5 mm of these structures. Figures 5-
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7 show the relationship between the location of the tumor margin relative to the fovea and the foveal dose of radiation obtained according to whether the tumor was large (Fig 5), medium (Fig 6) or small (Fig 7). These figures illustrate that treatment of an eye containing a large posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations is much more likely to result in a foveal radiation dose greater than 5000 rad than is treatment of a medium or small tumor located the same distance from the fovea. Figure 8 shows radiation dose to the lens as a function of tumor location relative to the lens for the entire group of 77 eyes managed by cobalt plaque therapy. This figure illustrates that treatment of an eye containing a posterior uveal melanoma with cobalt plaque radiotherapy according to our dose recommendations generally results in a radiation dose to the lens greater than 2500 rad if the distance between the point at the tumor base nearest the center of the lens is less than 10 mm. Figure 9 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 for the 133
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56 of the 77 eyes containing a posterior uveal melanoma which received a foveal radiation dose of less than 5,000 rad, as well as for the other 21 eyes which received a foveal radiation dose of more than 5000 rad. At the 36month follow-up point on the graph, 91 % (cumulative actuarial percentage) of the eyes which received less than 5,000 rad to the foveal retained visual acuity better than 20/200, but only 52% (cumulative actuarial percentage) of those which received more than 5,000 rad to the fovea retained visual acuity better than 20/200. Figure 10 presents the actuarial curve of the rate of preservation of visual acuity better than 20/200 for the 51 of the 77 eyes containing a posterior uveal melanoma which received a radiation dose of less than 5,000 rad to the optic disc, as well as for the other 26 eyes which received a disc radiation dose of more than 5,000 rad. At the 36-month follow-up point on the graph, 92% (cumulative actuarial percentage) of the eyes which received less than 5,000 rad to the optic disc retained visual acuity better than 20/200, but only 65% (cumulative actuarial percentage) of those which received more than 5,000 rad to the disc retained visual acuity better than 20/200.
Seven additional eyes experienced temporary severe visual loss during the period of follow-up. Six of these eyes developed a serous retinal detachment which extended to involve the fovea, but the subretinal fluid resolved spontaneously with visual recovery in every case. One eye developed a vitreous hemorrhage, which also resolved spontaneously with visual recovery. None of the 77 treated eyes in this series required secondary enucleation because of continued tumor growth or complications of radiation. Two of these patients died of metastatic uveal melanoma. No appreciable change in visual acuity occurred in any of the 77 fellow (control) eyes during the period of follow-up.
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DISCUSSION Although the reports by Stallard II and others 12,16 regarding the use of cobalt plaque radiotherapy for the treatment of posterior uveal melanomas indicate a high rate of local tumor control and systemic cure, several
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recent reports have stressed the frequent need for secondary enucleation and the common occurrence of radiation retinopathyl3-15 with resultant loss of visual acuity. The most comprehensive report to date of visual acuity data following cobalt plaque radiotherapy is MacFaul's follow-up report l8 of 107 patients treated in the Moorfield's Oncology Clinic between 1960 and 1975. Seventyeight of these patients were still living at the time of this follow-up and 51 still retained their eye. MacFaul found 4 of these 51 eyes (8%) had no light perception, 4 (8%) had light perception vision, 10 (20%) perceived hand motions, 13 (25%) had visual acuity between 20/200 and 20/120, and 20 (39%) retained visual acuity between 20/ 60 and 20/20. Of Stallard's first 100 patients treated by cobalt plaque therapy, 23 required secondary enucleation of the treated eye. The 5-year survival rate among these patients was 86%.19 Since these results are not corrected for unequal periods offollow-up by actuarial table meth-
ods, they are not directly comparable to the results of our study. Our study demonstrates that eyes containing medium and large posterior uveal melanomas with margins closer than 5 mm to the fovea and/or optic disc almost invariably receive a radiation dose to these sites of greater than 5,000 rad (Fig 1). Eyes receiving a radiation dose in excess of 5,000 rad to the fovea and/or optic disc commonly lose a substantial amount of vision within 2 to 3 years, but the visual prognosis appears to be relatively good for eyes receiving a radiation dose less than 5000 rad to these sites. Our study also shows that eyes treated by cobalt plaque radiotherapy for a large posterior uveal melanoma are more likely to suffer profound visual loss within the first 3 years of follow-up than are those treated by cobalt plaque radiotherapy for a medium or small melanoma. The predominant cause of severe visual loss in these patients appeared to be foveal radiation retinopathy. If the trend in visual loss that we have demonstrated during the first three years following cobalt plaque radiotherapy of posterior uveal melanomas continues, more patients will eventually lose a substantial portion of their pretreatment vision.
REFERENCES 1. Zimmerman lE, Mclean IW, Foster WD. Does enucleation of an eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells? Br J Ophthalmol 1978; 62:420-5. 2. Zimmerman lE, Mclean IW. An evaluation of enucleation in the management of uveal melanomas. Am J Ophthalmol1979; 87:74160. 3. Gass JOM. Observation of suspected choroidal and ciliary body melanomas for evidence of growth prior to enucleation. Ophthalmology 1980; 87:523-8. 4. Vogel MH. Treatment of malignant choroidal melanomas with photocoagulation. Evaluation of 1O·year follow-up data. Am J Ophthalmol 1972; 74:1-11.
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5. Peyman GA, Raichand M. Full-thickness eye wall resection of choroidal neoplasms. Ophthalmology 1979; 86:1024-36. 6. Ellsworth RM. Cobalt plaques for melanoma of the choroid. In: Jakobiec FA, Ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 76-9. 7. Packer S, Rotman M. Radiotherapy of choroidal melanoma with iodine125. Ophthalmology 1980; 87:582-90. 8. Gragoudas ES, Goitein M, Verhey L, et al. Proton beam irradiation: an altemative to enucleation for intraocular melanomas. Ophthalmology 1980; 87:571-81. 9. Char DH, Castro JR, Quivey JM, et al. Helium ion charged particle therapy for choroidal melanoma. Ophthalmology 1980; 87:565-70. 10. Moore RF. Choroidal sarcoma treated by intraocular insertion of radon seeds. Br J Ophthalmol 1930; 14:145-52. 11. Stallard HB. Radiotherapy for malignant melanoma of the choroid. Br J Ophthalmol 1966; 50:147-55. 12. Long RS, Galin MA, Rotman M. Conservative treatment of intraocular melanomas. Trans Am Acad Ophthalmol Otolaryngol1971; 75:8493.
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13. MacFaul PA, Bedford MA. Ocular complications after therapeutic irradiation. Br J Ophthalmol 1970; 54:237-47. 14. Bedford MA, Bedotto C, MacFaul PA. Radiation retinopathy after the application of a cobalt plaque; report of three cases. Br J Ophthalmol 1970; 54:505-9. 15. Chat DH, Lonn L1, Margolis LW. Complications of cobalt plaque therapy of choroidal melanomas. Am J Ophthalmol 1977; 84:53641. 16. Shields JA, Augsburger JJ, Brady LW, Day JL. Cobalt plaque therapy of posterior uveal melanomas. Ophthalmology 1982; 89:1201-7. 17. Hillis A. Improving reporting of follow-up data. Am J Ophthalmol1982; 93:250-3. 18. MacFaul PA. Local radiotherapy in the treatment of malignant melanoma of the choroid. Trans Ophthalmol Soc U K 1977; 97:421-7. 19. MacFaul PA, Morgan G. Histopathological changes in malignant melanomas of the choroid after cobalt plaque therapy. Br J Ophthalmol 1977; 61:221-8.