Transpupillary thermotherapy in choroidal melanomas.

OBJECTIVE: To determine safety and efficacy of transpupillary thermotherapy (TTT) as a new treatment for choroidal melanoma. METHODS AND PATIENTS: To perform TTT, diode laser energy at 810 nm was used with a beam diameter of 1.5 to 4.5 mm for a 1-minute exposure. All 12 patients had choroidal melanoma. Six had had insufficient response to ruthenium 106 (106Ru) brachytherapy. Three patients with tumors more than 5 mm in height were treated simultaneously with 106Ru and TTT. Three patients with juxtapapillary or macular tumors were treated by TTT only. RESULTS: All but one tumor exhibited a reduction of tumor height in a follow-up period of 3 to 14 months. Side effects were minimal. Severe visual loss occurred in two patients due to radiation retinopathy, in two patients whose foveas were included in the TTT area, and in one patient resulting from a serous retinal detachment that extended over the posterior pole. CONCLUSIONS: Treatment with TTT may be useful as a complementary modality to brachytherapy. A longer follow-up period is required for final evaluation.

Results of ruthenium irradiation of uveal melanoma.

The follow-up results are presented for the radiotherapeutic treatment of 49 patients with uveal eye melanoma using ruthenium-106 (106Ru/106Rh) applicators. Graded doses were applied and the degree of regression was found to be correlated with the dose at the top of the tumour. Complete regression is found in 66% of the patients treated with a top dose above 150 Gy, in which case the initial tumour prominence diminishes in about three years to a stable disease or to a flat scar. At this dose a marginal increase in complications was observed as compared with lower dose groups. Useful vision could be preserved in 75% of the eyes.

Transpupillary thermotherapy (TTT) by infrared irradiation of choroidal melanoma.

We studied the destructive effect of hyperthermia at sub-photocoagulation level of 45-60 degrees C on melanomas. Optimal conditions for spreading of heat into tissue are a wavelength of 700-900 nm, a temperature of 45-60 degrees C, an exposure time of 1 minute or more, and a beam diameter of several millimeters. In hamsters with subcutaneous melanomas we obtained a tumour necrosis of 6 mm depth at 60 degrees C and one minute exposure time. We performed transpupillary thermotherapy (TTT) with a diode laser at 810 nm in patients with choroidal melanomas prior to enucleation. Treatment is based on the fortunate situation that irradiation at this wavelength combines optimal tissue penetration with a low absorption by clear ocular media of 5% or less. In 3 TTT-treated eyes histopathology showed a depth of necrosis of 0.9, 3.4, and 3.9 mm. TTT may become a new useful treatment modality for choroidal melanoma but its ultimate value has yet to be assessed.

Iris nevi and melanomas: a clinical follow-up study.

A follow-up study of 113 patients with suspicious iris nevi who were referred to our clinic between 1973 and 1991 was carried out by: reviewing their clinical records, fluorescein angiography, obtaining recent data with cooperation of their own or the referring ophthalmologist and contacting patients for reexamination. After examination the diagnoses were: 64 suspicious nevi, 23 melanomas, 15 ciliary body tumors with iris involvement and 11 other pseudomelanomas. In the group of suspicious nevi 86% was localized in the inferior part and 66% in the temporal part of the iris; for the melanoma group these figures were 78% and 75% respectively. The chamber angle was more often involved in the melanoma group, 40% against 17% in the suspicious nevi group. In this group 11 cases (21.6%) showed growth during the follow-up (mean 10.6 years). In three cases the tumor was surgically removed, with as histopathologic diagnosis: 1 xanthogranuloma, 1 neurolemmoma and 1 possible melanoma. In the melanoma group 16 lesions (76%) showed growth during the follow-up (mean 7.2 years), in most cases within 5 years of the initial diagnosis. The lesion was surgically removed in 11 cases. The histopathologic diagnoses were: 8 melanomas, 1 xanthogranuloma, 1 possible melanoma and 1 metastasis of a skin melanoma. Our study shows that periodic ophthalmic check-ups are of great importance in the management of iris lesions suspect for melanoma.

MRI in eye tumors.

Thirty patients with intraocular tumors were examined with MRI. A clear demarcation was seen between the melanomas and other intraocular structures such as sclera, vitreous and ciliary body. Retinal detachment, hemorrhage or choroidal-retinal layer could be seen separated from the tumor. In all our patients investigated with MRI the absence of extraocular melanoma tissue was confirmed by histopathology or by the findings during surgery. The demarcation between tumor and sclera seemed more sensitive in MRI than in ultrasonography in establishing extrascleral extension. Our study showed that MRI can be a valuable addition to ultrasonography in detecting intraocular tumors or tumor simulating lesions.

[Immunoscintigraphy of choroid melanoma using monoclonal antibodies]. / Immunoscintigrafie van het choroideamelanoom met behulp van monoklonale antilichamen.

A prospective pilot study on immunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was performed in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma associated antigen were labelled with 740 mBq (20 MCi) of the radionuclide 99mTc and injected intravenously. Images were made with a gamma camera 6 hours after injection. With a double pinhole collimator radioactivity was counted thrice in both eyes 6 hours after injection. In 6 out of 17 patients (35.3%) the melanoma could be imaged with the gamma camera. With the double pinhole collimator a significantly higher activity was measured in the melanomatous eye in 13 out of 17 patients (76.5%). In four patients a false negative result was obtained. Considering these results immunoscintigraphy may be valuable in ocular melanoma diagnostics but its specific value still has to be assessed.

Radioimmunoscintigraphy with melanoma-associated monoclonal antibody fragments in choroidal melanoma.

A prospective pilot study on radioimmunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was carried out in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma-associated antigen were labeled with 740 mBq 99mTc and injected IV; images were made with a gamma camera at 6 h after injection. With a double-pinhole collimator, radioactivity was counted thrice in both eyes at 6 h after injection. In 6 of 16 patients (37.5%), the melanoma could be imaged with the gamma camera. With the double-pinhole collimator, a significantly higher activity was measured in the melanomatous eye in 13 of 16 patients (82.4%). In two patients a false negative result was obtained, and in one patient the difference between the left and right eye was not significant. Considering these results, radioimmunoscintigraphy may be valuable in ocular melanoma diagnostics, but the specificity of MoAb 225.28S needs to be assessed.

Ocular and orbital metastasis of cutaneous melanomas.

Two patients with orbital metastasis from cutaneous melanoma are described. In one patient the metastatic tumour was located in the iris, in the other one it was located in the lateral rectus muscle. Only symptomatic treatment is indicated as the term of survival is short.

Incorporation of [125I]-5-iodo-2-thiouracil in cultured hamster, rabbit, and human melanoma cells.

The incorporation of [2-14C]-2-thiouracil and a series of [125I]-5-iodo-2-thiouracils ([125I]ISUra(s)) into cultured Greene hamster melanoma cells was determined in order to establish their properties as false precursors in the melanin-biosynthetic pathway. The cold trichloroacetic acid-precipitable incorporation of [2-14C]-2-thiouracil as well as [125I]ISUra into melanoma cells after a 24- to 48-hr labeling period proved to be completely tyrosinase dependent (more than 99.5% inhibition could be achieved by 0.5 mM phenylthiourea). [125I]ISUra incorporation was 3-fold higher than was [2-14C]-2-thiouracil incorporation and was enhanced by 1 mM theophylline treatment. [125I]ISUra incorporation into hamster, rabbit, and human melanoma cells showed a linear relationship with cell melanin content. Methylation of the sulfur completely prevented the incorporation, while propylation but not methylation at position 6 resulted in lower incorporation. [125I]ISUra proved to be a marker for melanogenesis and may be useful in studies on the differentiation of cultured melanoma cells.