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Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI-PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose-expansion study of patients with argininosuccinate synthetase (ASS1)-deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m

Retinoblastoma is the most common malignant tumour of the eye in childhood, with nearly all bilateral tumours and around 17-18% of unilateral tumours due to an oncogenic mutation in the RB1 gene in the germline. Genetic testing in all cases enables accurate risk assessment and optimal clinical management for the affected individual, siblings, and future offspring. We carried out the first UK-wide audit of understanding of genetic testing in individuals with retinoblastoma. A total of 292 individuals aged 16-45 years were included. Patients with bilateral disease were significantly more likely to understand the implications of retinoblastoma for siblings and children. There was a significant association between not knowing the results of genetic testing or not understanding the implications and not having children, particularly in women. Surprisingly, this was also true for individuals treated for unilateral disease with a low risk of retinoblastoma for their offspring. We are concerned that individuals may be making life choices based on insufficient information regarding risks of retinoblastoma and reproductive options. We suggest that improvement in transition care is needed to enable individuals to make informed reproductive decisions and to ensure optimal care for children born at risk of retinoblastoma.

Background Retinoblastoma is the most common primary intraocular malignancy of childhood. Systemic chemotherapy is a common treatment for intraocular retinoblastoma, and laser treatment is used as adjuvant therapy during or immediately after chemotherapy courses in selected cases. Objectives To compare the effectiveness and safety of adding focal laser therapy to systemically-delivered chemotherapy in treating intraocular retinoblastoma. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), MEDLINE Ovid (1946 to 20 October 2016), Embase Ovid (1980 to 20 October 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 20 October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 20 October 2016, ClinicalTrials.gov (www.clinicaltrials.gov); searched 20 October 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 20 October 2016. We did not use any date or language restrictions in the electronic searches for trials. Selection criteria We searched for randomised controlled trials (RCTs) of systemic chemotherapy with versus without adjuvant laser therapy for postequatorial retinoblastoma. Data collection and analysis We planned to use standard methodological procedures expected by Cochrane. We planned to meta-analyse the primary outcome, that is the proportion of eyes with recurrence of tumours within three years from treatment Main results No studies met the inclusion criteria for this review. Authors' conclusions No evidence from randomised controlled trials was found to support or refute laser therapy in addition to systemic chemotherapy for postequatorial retinoblastoma.

Purpose To assess the anatomic retinal and choroidal features of choroidal naevi using swept-source optical coherence tomography (SS-OCT) and enhanced-depth optical coherence tomography (EDI-OCT). DESIGN Observational case series. Methods Patients with choroidal lesions underwent clinical examination, B-scan ultrasound and imaging with SS-OCT and EDI-OCT. Location, dimensions, clinical and OCT retinal and choroidal features were recorded. Descriptive statistics were used. Results Case series included 31 patients. 27/31 naevi imaged were melanotic and 4/31 amelanotic with a an overall median thickness of 0.7 mm. Naevus configuration was plateau in 17/31 cases, dome in 10/31 cases and mixed in 4/31 cases. RPE and photoreceptor layer disruption were noted in 14/31 cases and 13/31 had no retinal changes. Subretinal fluid was noted in 6/31 cases. Bruch`s membrane was found intact in 26/31 cases on both modalities. Intrinsic hyperreflectivity was noted in 29/31 cases on EDI-OCT and 30/31 cases on SS-OCT with less optical shadowing. The posterior margin of the naevus was visualized in 11/31 cases with SS-OCT and in 6/31 cases with EDI-OCT. Intratumour vessels were visualized in 28/31 cases with SS-OCT and 23/31 cases with EDI-OCT. For both modalities choriocapillaris appeared compressed and abnormal in 20/31 cases. Conclusions These preliminary results indicate that imaging of choroidal naevi with SS-OCT enables better visualization of intratumour vessels and the posterior margin.

1. Truncated salamander rod photoreceptors were internally perfused to investigate the action of cytoplasmic Ca2+ on cGMP-activated channels in the outer segment. 2. Switching from 1 microM Ca2+ to 0 Ca2+ increased the cGMP-activated current by a factor of 7.1 +/- 0.5 when measured in the first 60 s after the outer segment was opened to the bath, but only 2-fold after 5 min or more. This was attributed to the loss from the outer segment of a soluble factor required for Ca2+ to inhibit the cGMP-activated channel. 3. Short exposures to 0 Ca2+ caused an irreversible increase in the cGMP-activated current measured in 1 microM Ca2+, indicating that lowering [Ca2+] accelerated the loss of the channel inhibitor from the outer segment. 4. Channel activation occurred with a half-time of 6.7 s on switching to 0 Ca2+. Replacing 1 microM Ca2+ inhibited the current again with a half-time of 11.0 s. 5. The inhibition of the cGMP-activated current by Ca2+ could be described by a Hill curve with half-maximal suppression at 55 +/- 13 nM Ca2+ and a Hill coefficient of 1.4 +/- 0.4. 6. Addition of calmodulin (1 microM), or the calmodulin inhibitors mastoparan and calmidazolium (5 microM), did not alter the action of Ca2+ on the cGMP-activated current. 7. The increased affinity of the cGMP-activated channels in response to a fall in [Ca2+] has the magnitude, speed and Ca2+ dependence to suggest that it will promote recovery of the cGMP-activated current in response to the light-induced fall in [Ca2+] that normally occurs inside the outer segment.

tion has an efficacy of about 85% using cryosurgery or laser surgery, NVG has been reported to persist in 1.6% of treated eyes (Fernandez-Vigo et al. 1997). A pharmacological treatment directed against the angiogenic stimulus for neovascularization may represent an alternative or an adjunctive treatment for ischaemic retinal diseases. In fact, promising results have been reported recently for intravitreal bevacizumab in iris neovascularization (Avery 2006; Davidorf et al. 2006). The current case demonstrates that intravitreal bevacizumab injection may be associated with rapid regression of iris and angle neovascularization in the setting of NVG associated with diabetic retinopathy. A single injection was associated with medically controlled IOP for at least 8 weeks. Although only a single bevacizumab injection was administered in this case, repeated injection(s) may be needed for longer-term treatment. Intravitreal bevacizumab injections may represent a useful alternative treatment for patients with NVG in whom inadequate visualization precludes treatment by retinal photocoagulation. References