Management of choroidal metastases.

BACKGROUND: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS: A systematic review of literature was performed from 1974 to 2014. RESULTS: Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION: Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma.

BACKGROUND: Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma. METHODS: We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays. RESULTS: We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse. CONCLUSION: These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression.

Ultrasonographic follow-up of patients with choroidal melanoma following conservative treatment.

The authors assessed the regression of choroidal tumors, following irradiation treatment, by means of B scan sonography (Sonomed B 3000). Thirty-two patients were studied, 12 of whom underwent brachytherapy with 106Ru plaques and 20 of whom were treated with accelerated protons. After a follow-up period of 12 months, the following was observed: reduction of the thickness of the tumor (significantly greater in the tumors which underwent brachytherapy) and morphological and structural changes which consisted in a thinning of the tumor and an increased reflectivity.

Treatment of uncomplicated cases of rhegmatogenous retinal detachment with an expanding gas bubble.

We reviewed 55 consecutive cases of rhegmatogenous retinal detachment treated with pneumatic retinopexy as a primary procedure and followed up for a minimum of 1 year. 40 eyes were phakic, 11 aphakic and 4 pseudophakic. 0.6 ml of sulfur hexafluoride were injected into 42 eyes, while 0.3 ml of perfluoropropane were introduced into 13. Transconjunctival cryotherapy was performed in 51 eyes, while light coagulation was used as retinopexy after the retina was reattached in the remaining 4 cases. Of the 55 eyes undergoing treatment, 46 (83.6%) retinas were reattached with one operation. The benefits, complications and disadvantages of the procedure are reported.

[The proton radiotherapy of melanoma of the uvea. The technic, methodology and first clinical observations]. / La radioterapia del melanoma dell'uvea con protoni. Tecnica, metodologia e prime osservazioni cliniche.

Since June 1991, a Cyclotron unit with a proton beam of 65 MeV has been working at the Institute Antoine Lacassagne in Nice, France. An international cooperative group has been founded to guarantee the thorough exploitation of the facility through complete cooperation. From June 17 to December 20, 1991, 47 patients with uveal melanoma were treated; 4 of them entered the study by means of the Italian team and were treated in cooperation with the Cyclotron staff. Treatment modalities and preliminary observations are described.

Optimized macular recovery test for the early diagnosis and risk prediction of retinopathy in diabetics.

The authors present a clinical study on the macular recovery test, in a new optimized version, in normal subjects and in diabetic patients. The discriminating thresholds between normals and retinopathic diabetics and between non-retinopathic and retinopathic diabetics were statistically analyzed.

Classification of proliferative diabetic retinopathy.

Using panretinal fluorescein angiography, three patterns (A, B, C) of capillary nonperfusion were identified in 308 eyes with proliferative diabetic retinopathy. Statistical analysis showed that there was a significant association with different retinal complications and clinical parameters. Pattern A (83.7%: midperipheral location of capillary nonperfusion) occurs in type I and II diabetes and is associated with early retinal neovascularization and focal macular edema. Pattern B (8.1%: capillary exclusions disseminated on the whole retina) is typical of young type-I diabetics and is complicated by early disc new vessels and ischemic maculopathy. Pattern C (8.1%: capillary nonperfusion confined to the peripheral retina) is observed in type-I diabetic females and associated with multiple, retinal new vessels, without maculopathy. This study also demonstrated that eyes with pattern B retinal ischemia respond less well to laser treatment than eyes with other pattern types. Various pathogenetic factors could lead to these three distinct types of proliferative diabetic retinopathy.