AUSTRALIAN AND NEW ZEALAND STUDY OF PHOTODYNAMIC THERAPY IN CHOROIDAL AMELANOTIC MELANOMA.

PURPOSE: To evaluate the safety and efficacy of primary photodynamic therapy (PDT) for posterior choroidal amelanotic melanomas. METHODS: Patients with posterior choroidal amelanotic melanomas up to 6 mm in height were treated with PDT using verteporfin as the photosensitizing agent. Treatment was repeated every 3 months until the tumor was flat up to a maximum of 6 treatments. Tumor response and recurrence was assessed by clinical examination, photography, and ultrasonography. Patients were monitored 3 monthly for a minimum of 3 years. RESULTS: Thirty-six of 41 (88%) patients had complete regression after an initial course of PDT. Of them, 20 (56%) had no recurrence, 3 (8%) had recurrences that were successfully treated with further PDT, and 13 (36%) had recurrences that failed or were not amenable to further PDT. None of the measured baseline characteristics predicted treatment outcomes. There was no reduction in visual acuity due to PDT. The mean follow-up time was 3.5 years. CONCLUSION: In this large series, primary PDT was highly effective in achieving initial regression of posterior choroidal amelanotic melanomas. Photodynamic therapy is a vision-preserving treatment option for these tumors; however, patients need to be followed up closely because there is a significant rate of recurrence.

Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4.

Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors), supporting its role as a novel driver mutation in UM. PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ, consistent with PLCB4 being the canonical downstream target of the former gene products. Taken together these data suggest that the PLCB4 hotspot mutation is similarly a gain-of-function mutation leading to activation of the same signaling pathway, promoting UM tumorigenesis.

Seasonal variation in trachoma and bush flies in north-western Australian Aboriginal communities.

BACKGROUND: Among younger age groups trachoma (Chlamydia trachomatis) has been identified as a major cause of morbidity in Australian Aboriginal communities. North-western Australia has two seasons, referred to as the wet and the dry, and until recently most trachoma screening programmes were conducted during the dry season. This study compared the prevalence of trachoma between three Aboriginal communities, two in the west and one in the east Kimberleys with differences in adult bush fly (Musca vetustissima) populations between the wet and dry seasons. METHODS: All preschool and school-aged children in each community were screened for trachoma in February and July 1996 using the World Health Organization method for clinical assessment of trachoma. Flies were trapped fortnightly from September through to May (inclusive) using a wind-orientated fly trap. RESULTS: Two communities in the west Kimberleys had a significantly higher rate of trachoma during the wet season (14-59% in dry season compared with 46-69% in wet season). One community showed no difference but this was probably due to the reduced re-screening rate. Further-more, it was demonstrated that fly populations are so low during the dry season that they were untrappable; however, populations of bush fly significantly increased during the wet season (ranging from 6 to 146 flies per hectare per month). CONCLUSIONS: If bush fly populations are correlated with increased levels of trachoma, then measures aimed at augmenting public health plans for bush fly control may decrease the cross-infection rate. Additionally, based on the results of this study, wet season trachoma screening trips should be considered.