Differences in uveal melanomas between men and women from the British Isles

and showed more circumferential spread in ciliary body (Po0.001) and iris (P ¼ 0.003). Tumours in men were more likely to extend to within 3 mm of optic disc or fovea (46.3 vs 39.0%, Po0.001), showing more extensive optic-disc involvement (Po0.001). The median largest basal tumour diameter was 12.2 mm in men and 11.9 mm in women (P ¼ 0.001). The tumour thickness had a median of 4.4 mm and 3.8 mm in men and women, respectively (P ¼ 0.015). The 180 ciliary body tumours occurred in 112 women and 68 men. In these, the prevalence of extraocular spread was higher in women (19.6 vs 8.8%; P ¼ 0.052). The 175 iris melanomas were more common in women than men (103 vs 72, respectively). Conclusions In men, UMs tend to be larger and more posterior than in women

Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21–q24.3, 6p25.1–p21.2, 21q21.2–q21.3 and 21q22.13–q22.3 and loss of 1p36.33–p34.3, 1p31.1–p21.2, 6q16.2–q25.3 and 8p23.3–p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3–p22.3 and 8q23.2–q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM

Efficacy and timing of adjunctive therapy in the anti-VEGF treatment regimen for macular oedema in retinal vein occlusion:12-month real-world result

PurposeVarious combination treatment regimens have been tried to improve the short-term efficacy of intravitreal monotherapy for the treatment of macular oedema (MO) secondary to retinal vein occlusion (RVO). Our study introduces the RandOL protocol (Ranibizumab and Ozurdex with Laser photocoagulation) of initial anti-VEGF therapy, controlling recurrent non-ischaemic MO with an intravitreal steroid and applying laser therapy to non-perfused retina. We describe our 12-month follow-up experience on timing for adjunctive therapy and real-world effectiveness and safety data.MethodsA retrospective analysis was carried out on 66 consecutive treatment-naive RVO patients with MO who received our RandOL treatment regimen. Baseline visual acuity (VA) and central retinal thickness (CRT) were compared with 12-month result.ResultsAt 12 months, 77% had significant VA improvement, 52% had ≥3-line improvement, and 15% were worse. Significant improvements in CRT were observed in 97% (baseline median CRT=531 μm (IQR 435-622) reduced to 245 μm (IQR 221-351, P<0.001) at 12 months); 76% achieved a dry fovea at 1 year. Mean number of total injections required was 5.5 (range 2-11) and 6% required ≥9 injections in 1 year. Although 70% received additional Ozurdex, 82% received ≥1 sessions of laser therapy. The BRVO subgroup achieved better VA and CRT improvement at 1 year, but small numbers limit definitive statistical conclusions.ConclusionsOur real-world results using a combination treatment protocol for RVO-related MO achieved similar desirable anatomical and visual outcomes as with a single-agent therapy with less intravitreal re-treatment rates at first year. Randomised controlled studies are needed to evaluate the role of laser and the ideal timing of combination therapy

Uveal melanoma UK national guidelines

The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours

Converting simulated total dry matter to fresh marketable yield for field vegetables at a range of nitrogen supply levels

Simultaneous analysis of economic and environmental performance of horticultural crop production requires qualified assumptions on the effect of management options, and particularly of nitrogen (N) fertilisation, on the net returns of the farm. Dynamic soil-plant-environment simulation models for agro-ecosystems are frequently applied to predict crop yield, generally as dry matter per area, and the environmental impact of production. Economic analysis requires conversion of yields to fresh marketable weight, which is not easy to calculate for vegetables, since different species have different properties and special market requirements. Furthermore, the marketable part of many vegetables is dependent on N availability during growth, which may lead to complete crop failure under sub-optimal N supply in tightly calculated N fertiliser regimes or low-input systems. In this paper we present two methods for converting simulated total dry matter to marketable fresh matter yield for various vegetables and European growth conditions, taking into consideration the effect of N supply: (i) a regression based function for vegetables sold as bulk or bunching ware and (ii) a population approach for piecewise sold row crops. For both methods, to be used in the context of a dynamic simulation model, parameter values were compiled from a literature survey. Implemented in such a model, both algorithms were tested against experimental field data, yielding an Index of Agreement of 0.80 for the regression strategy and 0.90 for the population strategy. Furthermore, the population strategy was capable of reflecting rather well the effect of crop spacing on yield and the effect of N supply on product grading

Clinical application of genetic testing for posterior uveal melanoma

Uveal melanoma is the most common primary intraocular tumor in adults, and it has a strong potential to metastasize. Traditionally, clinicopathological features of these tumors were used to provide a limited prediction of the metastatic risk. However, early genetic studies using karyotype analysis, fluorescence in situ hybridization, and comparative genetic hybridization of posterior uveal melanoma samples identified multiple chromosomal abnormalities associated with a higher risk of fatal metastasis. This correlation between specific genetic abnormalities in uveal melanoma and a patient’s risk for development of metastasis has recently been widely studied, and the development of new prognostic tests has allowed clinicians to predict this metastatic risk with increased accuracy. Such novel tests include gene expression profiling, which analyzes the RNA expression patterns of tumor cells, and multiplex ligation-dependent probe amplification, which detects deletions or and amplifications of DNA in tumor cells. This review discusses the current status of prognostic testing techniques available to clinicians and patients for posterior uveal melanomas