Microwave diathermy of the retina and choroid.

Microwaves were used to induce chorioretinal scar formation in normal rabbit eyes. We have developed a directional 6.8-gigahertz microwave applicator with a rectangular aperture. It was designed to mimic the shape and function of a T-shaped scleral depressor. For treatment, the applicator was placed on the conjunctiva over the sclera. Then, indentation was used to visualize probe placement during indirect ophthalmoscopy. Thermocouple-controlled heating was initiated such that conjunctival temperatures in a range of 51 degrees C to 65 degrees C were induced for 10 seconds per treatment. We found that treatment at temperatures of 51 degrees C or 52 degrees C for 10 seconds produced circular areas of acute retinal whitening. From these microwave-induced lesions, there evolved chorioretinal attenuation with and without evidence of retinal pigment epithelial hyperplasia. No evidence of scleral damage was noted at these thermal doses.

Photodynamic therapy for experimental intraocular melanoma using chloroaluminum sulfonated phthalocyanine.

Chloroaluminum sulfonated phthalocyanine (CASPc), a novel photosensitizing dye, was evaluated for treatment of experimental intraocular melanoma in 33 rabbit eyes. An argon ion pumped dye laser, operating at an emission of 675 nm, was used in a nonthermal mode to irradiate iris tumors in rabbits 24 hours after they received in intravenous dye injection (23 eyes). The effects of laser irradiation alone and dye alone were examined in ten control eyes. A threshold tumoricidal dose was established for photodynamic therapy with CASPc and laser irradiation. Vascular occlusion was produced in a well-circumscribed area corresponding to the boundaries of laser irradiation after CASPc injection. Tumors successfully treated with CASPc and laser irradiation were arrested in growth and exhibited no viable tumor cells on histologic examination. Control tumors continued rapid growth, unaffected by dye or laser. Our data indicate that CASPc demonstrates a strong photosensitizing effect on both tumor and normal tissue. These results suggest that CASPc is a potential photosensitizing compound that may be useful in the treatment of choroidal melanoma.

Hyperthermic treatment of intraocular tumors.

A 5.8-gigahertz (GHz) ophthalmic microwave applicator was used to treat choroidal melanoma (Green strain) in rabbits. High-frequency electromagnetic radiation provides a favorable dose distribution to induce local hyperthermia in the treatment of intraocular tumors. Heating of the neoplasm, while sparing normal ocular structures, is best accomplished by a transscleral approach. A hyperthermia plaque is placed on the sclera at the base of the intraocular tumor. Contact (resistive) heating and electromagnetic radiation (radiofrequency and microwave) are best suited to a plaque technique. The advantages of electromagnetic heat induction, as compared with contact heating, are twofold: the depth of hyperthermic penetration can be modulated by frequency selection, and the tissues with low water content (sclera) remain relatively unaffected by microwaves. The 5.8-GHz ophthalmic microwave applicator satisfies the requirements for local hyperthermic treatment of intraocular tumors.

Thermoradiotherapy for intraocular tumors.

We have developed and used a thermoradiotherapy (TRT) plaque to treat choroidal melanoma (Greene strain) in rabbits. A dual-therapy scleral plaque delivers localized hyperthermia (4.8-gigahertz microwave) and ionizing radiation (iodine I 125). Transscleral treatment involves placement of a TRT plaque on bare sclera at the base of an intraocular tumor. Therapeutic doses of ionizing and hyperthermic radiation are then simultaneously delivered to the intraocular tumor. Sparing of normal ocular structures outside the treatment area after the combined therapy has been noted on clinical, gross, and histologic examinations. Our study suggests that the TRT plaque described satisfies the requirements for dual-modality treatment of choroidal melanoma.

Proton beam irradiation and hyperthermia. Effects on experimental choroidal melanoma.

Ultrasonically induced hyperthermia (4.75 MHz) and proton irradiation (160 meV) were evaluated alone and combined to treat experimental choroidal melanoma in 58 rabbit eyes. Threshold tumoricidal doses were established for each modality. Therapy was performed combining subthreshold doses of heat and radiation. Focused ultrasonic energy via an external beam was found to deliver well-localized heat to an intraocular tumor. Ectopic temperature elevations due to soft-tissue-bone interfaces were alleviated by modifying beam alignment. The results indicate that hyperthermia (43 degrees C for one hour) potentiated the tumoricidal effects of radiation, while sparing normal ocular structures. Therefore, we believe that experimental hyperthermia is suitable as an adjuvant treatment modality. This shows that ultrasound hyperthermia has the potential to increase the efficacy of proton irradiation by lowering radiation doses and thus decreasing posttreatment ocular morbidity in human intraocular malignancies.

Scleral hyperplasia induced by heat.

We evaluated low-level heating as a stimulus to induce hyperplasia of normal rabbit sclera. Heat treatments were administered by placing an etched-element heater on bare sclera. Contact thermotherapy with a conductive device provided a favorable dose distribution for local scleral heating. A purely conductive heat source was selected to minimize intraocular heat penetration and to determine whether the scleral reaction was a primary thermal effect. Histologic examination of treated specimens showed thickening of normal rabbit sclera with preservation of the underlying normal ocular structures. Electron microscopic examination of treated sclera showed newly formed collagen fibrils adjacent to sclerocytes. These fibroblasts were activated, as manifested by well-developed rough-surfaced endoplasmic reticulum and hypertrophic Golgi complexes.

Effect of hyperthermia on experimental choroidal melanoma.

Thirty-five rabbit eyes were implanted subchoroidally with Greene's hamster melanoma. When the tumours reached a base diameter of 5 mm, they were treated with ultrasonically induced hyperthermia with a range of temperatures and exposure durations (43-67 degrees C and 75 s to 60 min). Of the 23 treated eyes examined two months after treatment eight showed complete regression of the tumour. Seven showed initial tumour regression, but there was subsequent regrowth of tumour round the margins of the original mass. In eight eyes the tumour continued to grow, though in some cases the rate of growth appeared to be slower than in the controls. In contrast, in all untreated animals the tumour grew to fill the vitreous cavity. These preliminary findings indicate that ultrasonically induced hyperthermia can be an effective local treatment of this intraocular tumour model.

Proton beam irradiation for treatment of experimental human retinoblastoma.

Proton beam irradiation was used to treat human retinoblastoma (Y-79 cell line) grown subcutaneously in the athymic "nude" mouse. Thirty-four tumors were included in the experimental groups, of which twenty-three were irradiated and eleven served as controls. Tumors were irradiated with protons produced at the 160 megavolts Harvard cyclotron. The dose delivered to the tumor ranged from 7.5 to 27.5 proton gray in a single treatment, and 25.0 proton gray delivered in two fractions separated by 24 hours. Reduction of tumor growth was significantly greater than controls (p less than 0.001) with treatment doses greater than or equal to 17.5 proton gray. Histologic examination revealed a marked decrease of mitotic activity in all specimens examined 48 hours after treatment at these higher doses. Total regression without evidence of remaining malignant cells was noted in three tumors treated at 17.5 proton gray or above. Our results indicate that human retinoblastoma in a murine host, with a tumor mass similar to that seen in a clinical setting, is sensitive to radiation by high energy protons.

[Sub-choroidal implanted Greene melanoma: an animal experiment model for malignant choroid melanoma]. / Das subchorioidal implantierte Greene-Melanom: Ein tierexperimentelles Modell für das maligne Adherhautmelanom.

A modified technique for subchoroidal transplantation of amelanotic Greene melanoma cells and the intraocular growth patterns of this tumor in rabbit eyes are described. Tumor fragments were implanted via a scleral tunnel in 71 rabbit eyes, with 64 successful tumor growths, producing a prominent, circumscribed choroidal mass within 12-14 days of surgery. Choroidal Greene melanoma in rabbits resembles human epithelioid uveal melanoma in both its growth patterns and morphologic characteristics. The authors' implantation technique guarantees reliable growth of choroidal tumors with easily reproducible size and location. The experimental choroidal melanoma model is particularly valuable in clinical studies where a large number of tumors, with limited variation, is necessary for different experimental groups.