[Treatment of intraocular melanoma: new concepts]. / Traitement du mélanome intraoculaire: nouveaux concepts.

The management of posterior uveal melanoma has evolved tremendously for the past decades and, more recently, there is a trend toward more focal conservative treatment. Transpupillary thermotherapy (TTT) with infrared diode laser (810 nm.) is the newest modality used as primary treatment or as complementary method to radiotherapy or surgical resection in very selected cases of choroidal melanoma. Plaque radiotherapy or charged-particle irradiation is particularly recommended for medium- or small-sized uveal melanoma not suitable to TTT or resection. Special custom-designed plaque radiotherapy (iodine-125) can be used for iris, ciliary body or juxta-paillary choroidal melanoma. The tumor control rate after plaque or charged-particle radiotherapy appears to be similar, but charged-particle irradiation may produce worse anterior segment complications than plaque radiotherapy. Stereotatic radiation therapy for choroidal melanomas may be effective in controlling tumor growth but the number of patients treated with the approach is too small to draw strong conclusions. Local tumor resection using trans-scleral resection is mainly suitable for selected iris, ciliary body, or anterior choroidal melanoma, particularly with smaller basal dimensions and greater thickness. Combined therapies (radiotherapy plus TTT, tumor resection plus TTT) appears to be more effective in decreasing the incidence of intraocular tumor recurrence. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.

[Transpupillary thermotherapy for treatment of choroidal melanomas]. / Thermothérapie transpupillaire dans le traitement du mélanome de la choroïde.

PURPOSE: To report the results of transpupillary thermotherapy (TTT) for selected posterior pole choroïdal melanomas. MATERIAL AND METHODS: Prospective study including 56 patients (mean age of 61 years) with choroidal melanoma treated with TTT. All treated tumors had either documented growth or clinical risk factors for future growth and for metastasis. The injection of infracyanine green (I CG) was randomized. RESULTS: The mean initial tumor basal diameter was 7.8 mm and tumor thickness was 3 mm. Twenty-seven tumors (48%) touched the optic disc and sixteen (29%) were under the fovea. Among these 56 patients with choroidal melanoma, 47 patients (84%) presented with primary choroidal melanoma. 9 tumors (16%) were late recurrences after conservative treatment. A mean of three treatment sessions was delivered. After a mean follow-up of 30 months, tumor regrowth was documented in 4 patients (7%) and the visual acuity was the same than the pretreatment acuity in 26 eyes (47%). The mean final thickness was 1.8 mm (percent reduction of tumor thickness was 39%). Intraocular complications included retinal fibrosis and/of retinal striae in 12 eyes (22%) and vascular occlusion in 14 eyes (25%). No statistical impact of ICG administration on the tumor regression was demonstrated. CONCLUSIONS: This series confirms the efficacy of transpupillary thermotherapy in the management of selected posterior pole choroïdal melanomas.

[Choroidal melanoma: current therapeutic approaches]. / Approches thérapeutiques actuelles du mélanome de la choroïde.

The management of posterior uveal melanoma has evolved tremendously over the past decades and more recently there has been a trend toward more focal conservative treatment. Transpupillary thermotherapy (TTT) with infrared diode laser (810nm) is the newest modality used as primary treatment or as a complement to radiotherapy or surgical resection in selected cases of choroidal melanoma. Plaque radiotherapy or charged-particle irradiation is particularly recommended for medium- or small-sized uveal melanoma not suitable to TTT or resection. Special custom-designed plaque radiotherapy (iodine-125) can be used for the iris and ciliary body, or in juxtapaillary choroidal melanoma. The tumor control rate after plaque or charged-particle radiotherapy appears to be similar but charged-particle irradiation may produce worse anterior-segment complications than plaque radiotherapy. Stereotactic radiation therapy for choroidal melanoma may be effective in controlling tumor growth, but the number of patients treated with this approach is too small to draw solid conclusions. Local tumor resection using trans-scleral resection is mainly suitable for selected iris, ciliary body, or anterior choroidal melanoma, particularly with smaller basal dimensions and greater thickness. Endoresection may preserve central vision or temporal field when radiotherapy would be expected to cause optic neuropathy. Longer follow-up is necessary to establish the efficacy of tumor control. Combined therapies (radiotherapy plus TTT or tumor resection plus TTT) appear to be more effective in decreasing the incidence of intraocular tumor recurrence. Enucleation is still performed for large uveal melanoma when there is no hope of regaining useful vision. Based on the published ophthalmology literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.

[Transpupillary thermotherapy in the treatment of choroid melanoma]. / Thermothérapie transpupillaire dans le traitement du mélanome de la choroïde.

PURPOSE: To report the results of primary transpupillary thermotherapy (TTT) for selected posterior pole choroidal melanomas. MATERIAL AND METHODS: Prospective non randomized study including 34 patients with choroidal melanoma treated with TTT using near-infrared radiation (810 nm) delivered from the diode laser. All treated tumors had either documented growth or clinical risk factors for future growth and/or metastasis. The treatment was delivered using a specially modified infrared diode laser through a slit lamp adaptor. A contact lens was placed on the cornea to view the fundus and focus the laser beam. Treatment was initiated using a 60-second exposure and a low energy level at 300 mW with a 3.0 mm beam width. The energy was raised stepwise by 50 to 100 mW until the surface of the tumor develop a light grayish discoloration. The TTT sessions were delivered at 3-month intervals. RESULTS: Among these 34 patients with choroidal melanoma, 29 patients presented with primary choroidal melanoma. Five tumors (15%) were late recurrences after conservative treatment. The mean initial tumor basal diameter was 7.2 mm and tumor thickness was 2.9 mm. Seventeen tumors (50%) touched the optic disc and 10 (29%) were under the fovea. After a mean of three treatment sessions and 20 months of follow-up, the mean tumor thickness gradually decreased to 2.3 mm at month 3 and 2.0 mm at month 6 after the initial TTT. The percent reduction of tumor thickness was 20% at month 3 and 29% at month 6. The mean final thickness was 1.7 mm. Treatment was successful in 33 patients (97%). Tumor regrowth was documented in one patient (3%) and required plaque radiotherapy. After treatment, visual acuity was the same or better than the pretreatment visual acuity in 21 eyes (62%) and worse in 13 eyes (38%). Intraocular complications included retinal traction in 12 eyes (34%) and vascular occlusion in 3 eyes (9%). CONCLUSION: This series confirms the efficacy of transpupillary thermotherapy in the management of selected posterior pole choroidal melanomas. Longer follow-up is still required to assess late local recurrence and the impact on metastatic disease.

Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma.

OBJECTIVE: The purpose of the study is to investigate chemoreduction and adjuvant treatment (AT) for retinoblastoma and its effect on complete retinal tumor control, vitreous seed control, and subretinal seed control. DESIGN: The study design was a prospective, nonrandomized clinical trial. PARTICIPANTS: There were 130 intraocular retinoblastomas in 52 eyes of 32 consecutive patients observed for at least 1 year after initiation of treatment. INTERVENTION: Treatment with chemoreduction using vincristine, etoposide, and carboplatin (VEC) and adjuvant treatment (+ AT) (cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, plaque radiation therapy, or external beam radiation therapy) were assessed. MAIN OUTCOME MEASURES: The effect of chemoreduction for 6 cycles (VEC x 6) versus fewer than 6 cycles (VEC x <6) on retinoblastoma control was analyzed. Furthermore, the impact of adjuvant treatment (+ AT) versus no adjuvant treatment (no AT) on retinoblastoma control was analyzed. RESULTS: Retinal tumors showed favorable initial regression with chemoreduction. Adjuvant treatment was applied to 93% of the retinal tumors after chemoreduction and only 2% recurred over the mean follow-up of 17 months (range 13-27 months). Vitreous seeds and subretinal seeds showed initial regression and often complete disappearance with chemoreduction. In those eyes with seeds before treatment, the addition of AT to VEC for 6 cycles decreased the vitreous seed recurrence from 75% to 0% (P = 0.04) and also decreased the subretinal seed recurrence from 67% to 0% (P = 0.003). More important, when considering that enucleation or external beam radiation therapy was the only other treatment option for these 52 eyes, the authors were successful in avoiding these methods in 42% of cases. Of the 36 eyes classified as Reese-Ellsworth group 5, there was 78% ocular salvage, and external beam radiation therapy was avoided in 25% of these eyes. There was a 100% ocular salvage in the group 5 eyes that received VEC for 6 cycles + AT to retinal tumors and seeds. CONCLUSIONS: Chemoreduction and AT to intraocular retinoblastoma and its seeds provides good retinal tumor control, even in eyes with advanced disease. Chemoreduction alone generally is not adequate to achieve complete tumor seed control. Cautious follow-up of affected patients is recommended because the risk for recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye.

Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture.

To our knowledge, there are no articles that describe the specific step-by-step details of the surgical removal of premalignant and malignant conjunctival tumors. We describe our current approach to the surgical management of squamous cell carcinoma (intraepithelial or invasive), localized melanoma, and primary acquired melanosis of the conjunctiva. The surgical method differs with limbal tumors, extralimbal tumors, and primary acquired melanosis. Limbal lesions are managed by localized alcohol corneal epitheliectomy, removal of the main mass by a partial lamellar scleroconjunctivectomy, and supplemental cryotherapy. Tumors located in the extralimbal conjunctiva are managed by alcohol application, wide circumferential surgical resection, and cryotherapy. Primary acquired melanosis is managed by alcohol epitheliectomy, removal of suspicious foci, quadrantic staging biopsies, and cryotherapy from the underside of the conjunctiva. In all cases, a "no touch" method is used and direct manipulation of the tumor is avoided to prevent tumor cell seeding into a new area. We have employed this technique on 109 patients with conjunctival squamous neoplasms and 137 patients with conjunctival melanoma, about 80 of which neoplasms were associated with primary acquired melanosis. Our observations suggest that well-planned initial surgical management using this technique decreases the chance of tumor recurrence for conjunctival melanoma and squamous cell carcinoma. We describe a detailed stepwise approach to the surgical management of conjunctival neoplasms. It requires meticulous clinical evaluation and complete removal of the tumor in one operation using a specific technique.

Diagnosis and treatment of uveal melanoma.

Most malignant melanomas in the ocular region arise in the uveal tract (iris, ciliary body, and choroid). Uveal melanoma generally has characteristic clinical features and the diagnosis can usually be made by an experienced ophthalmologist using slit lamp biomicroscopy or indirect ophthalmoscopy. Ancillary studies such as fluorescein angiography, ultrasonography, magnetic resonance imaging, and fine needle biopsy can occasionally be used to establish the diagnosis in atypical cases. Today, most affected patients are managed by specialists in ocular oncology. The management of uveal melanoma has been the subject of considerable controversy. Iris melanoma can usually be excised without enucleation of the affected eye. With regard to posterior uveal melanoma (ciliary body and choroid), enucleation of the affected eye was once the undisputed method of treatment. More recently, however, removal of the eye is performed less often and alternatives to enucleation have gained popularity. Several years ago, laser photocoagulation and plaque brachytherapy were the most popular alternatives to enucleation. Now, techniques of local tumor excision and transpupillary thermotherapy are gaining popularity in selected cases. Even more recently, various combinations of these methods have been judiciously used in many instances. The selected method of treatment in a given case depends on a number of complex clinical factors. Philosophies regarding the management of these lesions continue to change. This review covers the current diagnosis and management of uveal melanoma with emphasis on methods of management.

Chemoreduction in the initial management of intraocular retinoblastoma.

BACKGROUND: Chemoreduction is a method of reducing tumor volume to allow for more focused, less damaging therapeutic measures. OBJECTIVE: To determine whether chemoreduction could be used to decrease the size of retinoblastoma so that enucleation or external beam radiotherapy could be avoided and more conservative modalities employed. METHODS: A prospective pilot study was performed to assess the effectiveness of a 2-month chemoreduction regimen of vincristine sulfate, etoposide, and carboplatin in patients with retinoblastoma. The study included 20 patients with 54 tumors in 31 eyes. RESULTS: At the initial examination, the mean tumor base was 12 mm and the thickness, 7 mm. Vitreous seeds were present in 14 eyes (45%). A secondary retinal detachment was present in 24 eyes (77%) and, when present, involved a mean of 71% of the retina. In 11 eyes (36%) the retina was totally detached with serous subretinal fluid. After 2 months of chemoreduction, all 54 tumors showed regression in size, and 48 (89%) showed evidence of calcification. The mean tumor base was 8 mm and the thickness, 4 mm. Overall, there was a mean 35% decrease in base and 49% decrease in thickness of the tumor at the end of the treatment period. A complete response was found in 25 tumors (46%) and a partial response in 29 (54%). The subretinal fluid had resolved completely in 50% of the cases (12/24 eyes), and, in the 11 eyes with total retinal detachment, the subretinal fluid had completely resolved, leaving flat retina, in 6 eyes (54%). The vitreous seeds demonstrated some degree of regression in all cases, and in 5 eyes there was 90% to 100% calcification of the seeds. Short-term systemic toxic effects were mild (transient bone marrow suppression). Enucleation was avoided in all cases; external beam radiotherapy was necessary in 9 eyes because of diffuse vitreous seeds. The remaining 22 eyes were treated with local methods after chemoreduction. CONCLUSION: Tumor shrinkage with chemoreduction may allow treatment with less invasive measures, such as cryotherapy, laser photocoagulation, thermotherapy, or plaque radiotherapy, thereby avoiding enucleation and external beam radiotherapy.

Plaque radiotherapy for juxtapapillary choroidal melanoma. Visual acuity and survival outcome.

OBJECTIVES: To assess the effect of plaque radiotherapy on the visual acuity of patients with juxtapapillary choroidal melanoma and to determine the clinical predictive factors for radiation retinopathy, radiation papillopathy, local tumor recurrence, and distant metastasis. DESIGN: A retrospective review of the medical records of 93 patients with juxtapapillary choroidal melanoma who were treated initially with plaque radiotherapy. RESULTS: During a mean follow-up of 78 months, radiation retinopathy developed in 81 patients (87%) and radiation papillopathy developed in 48 patients (52%) after a mean interval of 21 and 27 months, respectively. The univariate variables that were significant predictors of radiation retinopathy were history of diabetes mellitus (P = .05) and use of a notched radioactive plaque (P = .04). The factors predictive of radiation papillopathy were age (> 45 years; P = .01), history of diabetes mellitus (P = .05), mushroom-shaped tumor configuration (P = .006), and nasal location of the tumor (P = .04). By using Kaplan-Meier survival curves, we found that the proportion of the 93 patients with radiation retinopathy was 87 (94%) at 5 years and with radiation papillopathy was 53 (57%) at 5 years. By using life-table analysis, we found that the proportion of the 93 patients who experienced a decrement of at least 3 lines of visual acuity was 67 (72%) by 50 to 60 months. Local tumor recurrence was documented in 14 patients (15%) after a mean interval of 41 months. The age of the patient (< 35 years; P = .02) and the superior (P = .004) and inferior (P = .05) locations of the tumor were predictive of local tumor recurrence. Distant metastasis developed in 11 patients (12%) after a mean interval of 44 months. The factors predictive of distant metastasis were a tumor with a basal diameter larger than 6.0 mm (P = .05), the superior location of the tumor (P = .01), and local tumor recurrence (P < .001). CONCLUSION: Based on these observations, plaque radiotherapy remains a potential option vs enucleation for the management of juxtapapillary choroidal melanoma.

New treatment modalities for retinoblastoma.

The management of retinoblastoma has evolved tremendously for the past century, and recently there is a trend toward focal conservative treatments. This trend is due primarily to the earlier detection of the disease when the tumors are in a smaller stage of development as well as to advanced, more focused treatment modalities. Enucleation is still used for advanced retinoblastoma, especially when there is a concern that there may be invasion of the optic nerve, choroid, or orbit. The hydroxyapatite implant has provided improved cosmetic rehabilitation of the socket after enucleation. External-beam radiotherapy continues to be an important method of treating advanced retinoblastoma, especially when there is diffuse vitreous seeding. Plaque radiotherapy is a useful tool for controlling medium or small retinoblastomas, especially tumors with focal vitreous seeding or those that recur after other methods have failed. Cryotherapy and photocoagulation provide excellent control of small tumors, and advanced laser delivery systems have improved the visualization and ease of treatment of retinoblastoma. Thermotherapy and chemothermotherapy are the newest focal methods that are showing promising results for small to medium-sized retinoblastoma. Recent developments with chemotherapy regimens have allowed dramatic control of intraocular retinoblastoma, and they play an important role in the initial management of many cases.

New treatment modalities for uveal melanoma.

The management of uveal melanoma has evolved tremendously for the past century, and more recently there is a trend toward more focal conservative treatment. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision with conservative treatment. Plaque radiotherapy is particularly recommended for medium- or small-sized uveal melanoma. Special custom-designed plaque radiotherapy can be used for iris, ciliary body, or juxtapapillary choroidal melanoma. Charged-particle irradiation constitutes an alternative treatment modality for posterior uveal melanoma. However, charged-particle therapy is limited by the availability of appropriate therapeutic facilities. Local tumor resection using lamellar sclerouvectomy is mainly suitable for selected iris, ciliary body, or anterior choroidal tumors with smaller basal dimension and greater thickness. Ablative laser photocoagulation is indicated for very selected cases of small posterior choroidal uveal melanoma. Combined plaque radiotherapy with indirect ophthalmoscope laser therapy appears to be a more effective local tumor treatment plan than plaque radiotherapy alone. Transpupillary thermotherapy is the newest modality used as primary treatment or as complementary method to brachytherapy for treatment of selected choroidal melanomas. Hyperthermia with infrared irradiation below photocoagulation level produces tumor necrosis with few ocular complications. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.