Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

Purpose: To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. Methods: In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Results: Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg ± 0.23) than in the dorzolamide/timolol group (17.3 mmHg ± 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. Conclusions: The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.publishersversionPeer reviewe

So close, yet so far : discrepancies between uveal and other melanomas. A Position Paper from UM Cure 2020

Despite much progress in our understanding of uveal melanoma (UM) over the past decades, this rare tumour is still often misclassified. Although UM, like other melanomas, is very probably derived from melanocytes, it is drastically different from cutaneous melanoma and most other melanoma subtypes in terms of epidemiology, aetiology, biology and clinical features, including an intriguing metastatic hepatotropism. UM carries distinctive prognostic chromosome alterations, somatic mutations and gene expression profiles, allowing an active tailored surveillance strategy and dedicated adjuvant clinical trials. There is no standard systemic treatment for disseminated UM at present. In contrast to cutaneous melanoma, UMs are not BRAF-mutated, thus curtailing the use of B-Raf inhibitors. Although these tumours are characterised by some immune infiltrates, immune checkpoint inhibitors are rarely effective, possibly due to a low mutation burden. UM patients across the world not only face rare cancer-related issues (e.g., specific management strategies, access to information and to expert centres), but also specific UM problems, which can be exacerbated by the common misconception that it is a subtype of cutaneous melanoma. As a European Consortium dedicated to research on UM and awareness on the disease, “UM Cure 2020” participants urge medical oncologists, pharmaceutical companies, and regulatory agencies to acknowledge UM as a melanoma with specific issues, in order to accelerate the development of new therapies for patients

The Pediatric Choroidal and Ciliary Body Melanoma Study A Survey by the European Ophthalmic Oncology Group

Purpose: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. Design: Retrospective, multicenter observational study. Participants: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. Methods: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. Main Outcome Measures: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. Results: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. Conclusions: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

Indocyanine green as a prospective sensitizer for photodynamic therapy of melanomas

Spectroscopic, photochemical and biological properties of indocyanine green (ICG) are presented. Light over 800 nm is effectively absorbed by ICG. This property as well as photochemical behaviour of ICG make it a very suitable dye for photodynamic treatment of melanoma cells. Cytotoxicity of ICG itself and the effect of photodynamic therapy (PDT) were evaluated by following the growth of human (SKMEL 188) and mouse (S91) melanoma cells. The surviving fraction of the cells irradiated (lambda(ex) = 830 nm) vs non-irradiated, treated with the same dose of ICG, is significantly decreased (5- to 10-fold). These results show that ICG is a very promising dye for photodynamic therapy of melanomas

Downregulation of Polo-like kinase-1 (PLK-1) expression is associated with poor clinical outcome in uveal melanoma patients

Introduction. Uveal melanoma (UM) is the most common primary eye tumour in adults. Distant metastases are seen in 50% of cases regardless of treatment, which contributes to high mortality rates. Polo-like kinase-1 (PLK-1) is a protein regulator of mitotic entry and cytokinesis. Increased PLK-1 expression has been shown in different tumours, which makes its inhibition a potential treatment target. To date, no study has been published to discuss the prognostic role of PLK-1 expression in patients with uveal melanoma. Material and methods. We assessed by immunohistochemistry PLK-1 expression in uveal melanoma cells collected in 158 patients treated by primary enucleation. We determined the correlation between PLK-1 levels evaluated by the immunoreactivity scale (IRS) method and detailed clinical as well as histological parameters. Additionally, we determined the association between PLK-1 expression levels and long-term prognosis. Results. Elevated PLK-1 expression in tumour cells, defined as IRS > 2, was observed in 70% (111/158) of cases, whereas low expression or no expression was seen in the remaining 30% (47/158) of patients. There was a significant correlation between low PLK-1 expression and a higher clinical tumour stage (pT, p = 0.04) as well as a higher AJCC prognostic stage group (p = 0.037). We observed an inverse correlation between PLK-1 expression and tumour cell pigment content (p = 0.0019). There was no correlation between PLK-1 expression and other histological parameters such as mitotic rate or histological subtype. The Kaplan-Meier’s analysis demonstrated that low PLK-1 expression was associated with significantly reduced overall survival (p = 0.0058). A similar trend, albeit not significant, was observed for disease-free survival (p = 0.088). Conclusions. Downregulated PLK-1 expression is a negative prognostic factor in uveal melanoma. It warrants further, multicentre research on prognostic role of PLK-1 expression and possibility of PLK-1 inhibition in uveal melanoma

A diagram showing all proteins regulated in proton-irradiated BLM cells.

<p>The level of 17 proteins changed (>1.5×) in comparison with control. Thirteen proteins were upregulated (in black) and 4 were downregulated (in red). Here they are presented in four, not exclusive, groups: i) DNA repair and stress, ii) proliferation and survival control, iii) metabolic and iv) connected to motility and the cytoskeleton. ACTN 4 - α Actinin 4, Caprin-1 - Cytoplasmic activation/proliferation-associated protein-1, FAB-2 - Far upstream element binding protein 2, G3BP1 - RasGAP SH3-domain-binding protein 1, GADPH - Glyceraldehyde 3-phosphate dehydrogenase, MCM-7– Minichromosome Maintenance Protein 7, Moesin - Actin-regulatory protein, MVP - Major Vault Protein, PDCD6 - Programmed cell death 6, or apoptosis-linked gene-2, STRAP - Serine-threonine kinase receptor-associated protein, TIM - Triosephosphate isomerase, VCP – Transitional endoplasmic reticulum ATPase.</p

List of differentially regulated proteins from a comparison of proton beam irradiated and unirradiated BLM cells.

<p>Spots were compared by 2D stained with Colloidal Coomassie and proteins were identified using LC-MS/MS.</p><p>^a The spot location is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084621#pone-0084621-g002" target="_blank">Figure 2</a> ad 3.</p><p>^b Protein accession number from the UniProtKB/Swiss-Prot nonredundant protein database.</p><p>^c obtained sequence coverage.</p><p>^d Ratio calculated in relation to unirradiated control group.</p

The zoomed changes in the level of spots identified by MS in the two groups.

<p>Left panel – control group, Right panel –3 Gy irradiated group. Spot numbers as listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084621#pone-0084621-t001" target="_blank">Table 1</a>.</p