Nonepibulbar tumors more often recur locally and are associated with a shorter survival independent of other risk factors. Tumor thickness is also an important predictor of regional and distant metastases, as well as survival. A prospective study is needed to compare the effect of excision with radiotherapy and excision with cryotherapy on the number of local recurrences, exenteration rate, and survival.

Cerebroretinal vasculopathy, hereditary vascular retinopathy, and hereditary endotheliopathy, retinopathy, nephropathy and stroke are neurovascular syndromes initially described as distinct entities. Recently they were shown to be one disease caused by C-terminal frame-shift mutations in TREX1, which was termed 'retinal vasculopathy with cerebral leukodystrophy'. Here we defined the genetic and clinicopathologic spectrum of this clinically and pathophysiologically poorly characterized and frequently misdiagnosed fatal neurovascular disorder. We identified five different TREX1 mutations in 78 members from 11 unrelated families and by using a standardized study protocol we retrospectively reviewed and aggregated the associated clinical, neuroimaging, and pathology data. Findings were similar across mutations and families. Sixty-four mutation carriers had vascular retinopathy. Neuroimaging revealed (i) punctate, hyperintense, white matter lesions with or without nodular enhancement in 97% of them; (ii) rim-enhancing mass lesions in 84%; and (iii) calcifications in the white matter in 52%. Ninety per cent had clinical manifestations of brain disease, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). One mutation carrier had enhancing brain lesions and neurological features but unknown retinopathy status. Additional systemic features included liver disease (78%), anaemia (74%), nephropathy (61%), hypertension (60%), mild Raynaud's phenomenon (40%), and gastro-intestinal bleeding (27%). Mean (AE standard deviation) age at diagnosis was 42.9 AE 8.3 years and at death 53.1 AE 9.6 years. Pathological examination revealed systemic vasculopathy with luminal narrowing and multi-laminated basement membranes. The 13 mutation carriers without retinopathy or brain lesions were on average 8 years younger (mean age: 35.1 AE 10.6 years). Of them, 54% had mild Raynaud's phenomenon, 42% had migraine, and 23% had psychiatric disturbances. Retinal vasculopathy with cerebral leukodystrophy is an autosomal dominant systemic small-vessel disease due to specific TREX1 mutations and clinically primarily characterized by (i) visual impairment from vascular retinopathy; and (ii) neurological decline and premature death due to progressive enhancing cerebral white matter lesions. Impaired liver and kidney function, anaemia sometimes associated with gastrointestinal bleeding, hypertension, migraine, and Raynaud's phenomenon appear to be part of the clinical spectrum as well. Penetrance

Monosomy 3 in uveal melanoma is associated with the presence of an inflammatory phenotype, consisting of a high HLA class I and II expression as well as an increased number of tumor-infiltrating macrophages. In a multivariate Cox regression analysis, the presence of monosomy 3 was one of the best prognostic markers of metastatic disease and survival, although the follow-up time was short.

Aims-The eVect of transpupillary thermotherapy (TTT) on human choroidal melanomas was investigated by means of histopathology. Methods-Before enucleation TTT was performed in 11 eyes with a xenon arc photocoagulator with a red filter or a diode laser at 810 nm. The exposure time was 1 minute; the estimated temperature at the top of the tumour was about 65°C. Results-Seven of 11 tumours developed necrosis to a maximum depth of 3.9 mm with a sharp demarcation between the necrotic and the viable part of the tumour. The depth correlated with penetration of heat into the tumour. Scattered small haemorrhages in the transitional zone between the necrotic and the viable part of the tumour were observed in three eyes but large haemorrhages were absent. Ocular media were not aVected owing to the low rate of absorption of radiation at 810 nm. TTT did not cause significant scleral damage. Intrascleral tumour cells with a viable appearance were observed in one eye, where the tumour was almost totally necrotic. Conclusion-Results show that TTT has potential as a conservative therapeutic treatment for choroidal melanomas. (Br J Ophthalmol 1997;81:234-239) Enucleation as treatment of choroidal melanomas is partly replaced by radiotherapy with charged particles or brachytherapy with ruthenium-106 or iodine-125. Irradiation is associated with failures and complications since approximately 50% of eyes develop late complications after brachytherapy.

Local application of 5-Fluorouracil was practised on 5 patients. In 3 patients with multiple premalignant oculo-cutaneous lesions, two of whom had also premalignant epibulbar lesions, local 5% 5-Fu cream and/or 1% 5-Fu eyedrops were applied. In 2 other patients who had only premalignant lesions on the cornea and conjunctiva, 1% 5-Fu eyedrops were used only. In animal experiments 1% 5-Fu was not found to cause any damage to normal corneal and conjunctival epithelium. The frequency of the applications and the duration of the treatment were dependent on the location and extent of the lesions. Except for easily treatable lesions, caused by the separation of the tumour epithelium, no complications of local 5-Fu treatment were seen. The visual acuity improved in all 4 patients in whom the cornea was affected. In these premalignant conditions the diagnosis and assessment of the therapy were based on exfoliative cytology and biopsies.