[en] Prognostic indicators for the development of metastasis following proton beam irradiation of uveal melanomas were evaluated for 510 patients treated from 1975 to 1984. Thirty-three patients developed metastasis (6.5%) from 3 to 51 months following treatment. The primary site of metastasis was the liver in 28 cases (85%). Both demographic and clinical factors were considered. The three leading predictors of survival without metastasis after proton beam irradiation in order of importance were: (1) largest diameter of the tumor; (2) location of the anterior margin of the tumor; and (3) age at treatment. Worse prognosis was associated with largest tumor diameter greater than 15.0 mm, tumor involvement of the ciliary body and age at treatment older than 59 years

[en] Prognostic factors for visual loss following proton irradiation of uveal melanoma were evaluated for 440 eyes treated from 1975 to 1984, with visual acuity 20/200 or better before treatment. Analysis involved Kaplan-Meier survival curves and Cox proportional hazards analysis with visual outcome defined as worse than 20/200. Prognostic factors were tumor height: rate ratio (ratio of rate of visual loss for one category of the variable relative to the rate of visual loss for a reference category of that variable) of 5.26 (95% confidence interval, 2.66-10.39) for tumors greater than 5 mm compared to tumors 3.0 mm or less in height; distance of tumor from the optic disc and fovea: rate ratio 2.59 (1.63-4.11) for tumors 2DD or less from both the optic disc and fovea compared to those greater than 2 DD from these structures. Also predictive of visual loss were tumor location close to disc only, or close to fovea only, macular detachment, worse pretreatment vision, and higher radiation doses delivered to both the disc and fovea, and lens. Regression analysis using a visual acuity scale gave similar results

No abstract available

[en] Proton beam irradiation is one of the radiotherapeutic techniques currently used to manage uveal melanomas. Although this therapeutic modality has been in use for a decade and although nearly 500 patients have been so treated, there are only two published reports of the pathologic examination of these eyes. Key features found on pathologic examination of our patient's enucleated eye included vascular alterations in the tumor's blood supply, lymphocytic infiltrates, and lipoidal degeneration of tumor cells. The interval from therapy to enucleation in our patient was much longer than in the several previously reported cases, a factor allowing for the development of a more cumulative radiation effect on the tumor. The extent and degree of radiation-induced necrosis in our patient's tumor were more profound than in previous reports

[en] Fifteen owl monkeys (30 eyes) that received proton irradiation of discrete areas of the retina and choroid have been observed for 3 1/2 years or more after irradiation. The dose delivered to the retina varied from a single dose of 1600 to 4750 proton rads and from 10,250 to 18,250 rads delivered in five fractions over a period of one month. Fundus examination, fluorescein angiography, and light and electron microscopy revealed chorioretinal changes at the area of irradiation. The results of this study suggest that proton beam irradiation may markedly reduce delayed ocular complications, especially radiation retinopathy, which is common to other forms of radiotherapy in the treatment of intraocular tumors

[en] Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers

[en] Proximity to the disc and fovea is a risk factor for visual loss after proton beam irradiation of uveal melanomas. Of 562 eyes treated over a 10-year period with pretreatment visual acuity of 20/200 or better, 363 (64.6%) contained tumors within 2 disc diameters (DD) of the disc or fovea. Rates of visual loss after treatment to worse than 20/200 and causes of visual decline were evaluated using Kaplan-Meier analysis. Cumulative rates of visual loss among subjects with tumors near the disc or fovea were 33 and 47% 1 and 2 years after treatment compared to 17 and 28%, respectively, for subjects with tumors located farther from both structures. The leading cause of visual loss in the first year among eyes with tumors near the disc or fovea was retinal detachment. Controlling for other predictors of visual loss to worse than 20/200, location near the disc or fovea was independently related to visual loss primarily due to retinal detachment, cataract, and radiation retinopathy. Despite the unfavorable location of these tumors, over half of patients with 20/200 or better pretreatment visual acuity had useful vision 2 years after treatment

[en] Proton magnetic resonance imaging (¹H MRI) has emerged as a clinically useful tool for the diagnosis of intraocular tumors. During the last four years 1H MRI characteristics, including spin-lattice relaxation times (T1) and spin-spin relaxation times (T2), have been established for several types of tumors. The introduction of surface coils to the imaging process has significantly improved the quality of intraocular MR images, leading some clinicians to suggest that 1H MR images are preferable to CT scans. Another MRI technique, in which sodium-23 (²³Na) is imaged rather than protons, is now under development as tool for intraocular diagnosis. The potential of ²³Na MRI depends upon the high concentration and visibility of sodium in the vitreous body, and upon the apparent differences in sodium behavior in normal cells vs. tumor cells. The metabolism of normal ocular tissues and intraocular tumors may be probed noninvasively with phosphorus-31 MR spectroscopy (³¹P MRS). Much progress has been made during the last few years in understanding the appearance of ³¹P MR spectra of many types of healthy and diseased cells and tissues. Clinical application of this technique to the diagnosis and monitoring of intraocular tumors following conservative treatment will be dependent upon the development of spectroscopy techniques that collect information from the volume of interest (tumor) only. 54 references

[en] Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression

[en] A comparison was made of survival experiences for three groups with uveal melanoma: (1) 120 patients treated by proton beam irradiation from 1975 to 1981; (2) 235 patients treated by enucleation from 1953 to 1973 (enucleation group 1); and (3) 161 patients treated by enucleation from 1975 to 1981 (enucleation group 2). The following variables were predictive of melanoma-related deaths. Treatment: rate ratio (ratio of the rate of death for one category of the variable relative to the rate of death for another category) of 6.32 (95% confidence interval 1.70 to 23.51) for enucleation group 1 vs proton beam, 3.06 (0.81 to 11.54) for enucleation group 2 vs proton beam, and 2.07 (1.05 to 4.07) for enucleation group 1 vs enucleation group 2. Size: rate ratio of 3.61 (1.51 to 8.64) for large (16+ mm) vs small (less than 11 mm) tumors. Location: rate ratio of 3.19 (1.56 to 6.53) for tumors anterior vs posterior to the equator. When death from all causes was evaluated as the outcome, the estimated rate ratios were similar. When melanoma metastasis was evaluated as the outcome, the estimated rate ratios were reduced in magnitude