Uveal melanoma arises from melanocytes located in the uveal tract of the eye and is the most common primary intraocular tumor in adults. Metastatic liver disease is the overwhelming cause of death in uveal melanoma patients, with almost 50% of patients developing liver metastases up to 15 years after diagnosis. Most of these patients do not present with any evidence of overt metastasis at the time of initial diagnosis although it is assumed that they have undetectable micrometastases. Currently, there are no therapeutic modalities to prevent or efficiently treat the metastatic disease in uveal melanoma patients. Recent discoveries have shed light on the molecular pathways that may contribute to the progression of liver metastasis. The aim of this review is to describe new insights into the genetic and molecular pathways that may play a role in the development of liver metastases in uveal melanoma patients.

Purpose:To examine the immunohistochemical profile of heat shock protein 90 (Hsp90) in uveal melanoma and the cytotoxicity of an Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in uveal melanoma cell lines. Experimental Design: Hsp90 expression was determined by immunohistochemistry in 44 paraffin-embedded sections of primary human uveal melanoma and in five uveal melanoma cell lines (92.1, OCM-1, MKT-BR, SP6.5, and UW-1). Sulforhodamine B^based proliferation assay was used to compare uveal melanoma cell growth with a range of concentrations of 17-AAG. Changes in cell migration, invasion, cell cycle fractions, and apoptotic activity were also evaluated. Expression of intracellular proteins was determined by Western blot analysis after 17-AAG exposure.Results: Immunohistochemical expression of Hsp90 was identified in 68% of the paraffinembedded sections and significantly associated with largest tumor dimension (P = 0.03). 17-AAG significantly reduced the proliferation rates of uveal melanoma cell lines, with concentrations of 100 to 0.1 Amol/L. 17-AAG also significantly reduced the migratory and invasive capabilities of uveal melanoma cell lines. Cell cycle analysis showed that 17-AAG induced accumulations of cells in G 1 . Caspase-3 protease activity analysis, a marker for apoptosis, showed a significant increase after drug exposure. The cytotoxic effect of 17-AAG was associated with decreased levels of phosphorylated Akt and cyclin-dependent kinase 4. Conclusions: The immunohistochemical expression of Hsp90 in uveal melanoma indicates worse prognosis.To the best of our knowledge, this is the first report showing the inhibitory effect on uveal melanoma cells using 17-AAG to target Hsp90. Therefore, Hsp90 may be used as a potential target for treatment of patients with uveal melanoma.

Aims: To compare the analgesic properties of lidocaine 2% jelly versus sub-Tenon's anaesthesia with lidocaine 2% without adrenaline (epinephrine) for trabeculectomy surgery. Methods: A prospective randomised clinical trial. 59 consecutive patients scheduled for trabeculectomy at the Toronto Western Hospital were randomly assigned to topical unpreserved lidocaine 2% jelly or sub-Tenon's anaesthesia with 2% lidocaine. Both groups received a standardised sedative consisting of midazolam, fentanyl. and/or propofol. The visual analogue scale was utilised to measure intraoperative pain. Patient comfort, physician assessment of intraoperative patient compliance, volume of local anaesthetic used, need for supplemental anaesthesia, and any complications were recorded. The two groups were compared using the Student's t test. Results: The sub-Tenon's anaesthesia group and the lidocaine 2% jelly group did not vary significantly in subjective pain score (18.3 (SD 16.2) v 19.8 (12.4) respectively, p = 0.739) and surgeons' satisfaction scale (3.6 (0.7) and 3.8 (0.6) respectively, p = 0.328). Four patients required additional anaesthesia, all of them in the sub-Tenon's group. Conclusion: Topical lidocaine 2% jelly is as effective as subTenon's anaesthesia for pain control in patients undergoing trabeculectomy. Lidocaine 2% jelly is similar to sub-Tenon's anaesthesia in patient comfort and surgeon satisfaction.

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