The Silk Vista Baby - The UK experience.

BACKGROUND: The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB. MATERIALS AND METHODS: We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected. RESULTS: We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30-72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1-36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm).An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%).Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) - one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up. CONCLUSION: The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

Treatment of acute aneurysmal subarachnoid haemorrhage with primary flow diversion: 5-year single-centre experience.

AIM: To evaluate the safety and efficacy of treatment of patients presenting with acute aneurysmal subarachnoid haemorrhage (SAH) with primary flow-diverting stents (FDS; with or without adjuncts), with comparison to the published literature. MATERIALS AND METHODS: A retrospective single-centre review was undertaken of prospectively obtained data on patients treated for SAH over a 60-month period. Of 354 patients treated for SAH during that time period, 24 patients with a total of 25 aneurysms were identified. Baseline patient demographics were recorded and clinical and imaging outcomes assessed. RESULTS: Eighty-eight per cent (22/25) of the aneurysms were completely occluded (Raymond-Roy 1) at mean 12-month follow-up. The minor complication rate was 12.5% (3/24) without permanent morbidity. Mortality rate was 4% (1/25) after one patient died following aneurysmal rebleed on day 7 post-procedure. Forty-two per cent (10/24) of patients had a high-pressure shunt placed prior to endovascular treatment, no haemorrhagic complications of neurosurgical intervention were observed. CONCLUSION: The necessity of dual antiplatelet therapy (DAPT) therapy when deploying FDS will rightly continue to limit their use in the acutely ruptured setting to a case-by-case basis whereby other treatment options are deemed unsafe. Methods employed to minimise subsequent haemorrhagic risks from DAPT in these patients may be worthy of further investigation.

Fresh frozen amniotic membrane for conjunctival reconstruction after excision of neoplastic and presumed neoplastic conjunctival lesions.

PurposeSuspicious neoplastic conjunctival lesions often require wide excision with tumour-free margins, leaving significant conjunctival defects requiring reconstruction. In this study we report the results of using fresh frozen amniotic membrane grafts (AMG) after wide excision of potentially malignant lesions.MethodsRetrospective review of 53 patients; between January 2011 and April 2014. Conjunctival lesions were excised with a non-touch technique (2 mm margin) and sent for histopathological analysis. The surgical margins were treated with cryotherapy and a fresh frozen AMG was used to cover the defect. The main features examined were for any signs of recurrence, the conjunctivalisation of the AMG, complications and cosmetic appearance.ResultsFifty-three patients; 35 males and 18 females. Mean age was 54.9 (range 19-88). The mean follow up to January 2015 for all lesions was 21.4 months (range 8-48 months). The most common lesions were invasive malignant melanoma. There were no local surgical complications in 77.3% of patients; minimal scarring (11.3%), symblepharon (11.3%), and granuloma (7.5%). Five patients with conjunctival melanoma developed in-transit metastasis and orbital extension, none of it was at the site of the AMG.ConclusionOur case series is the largest reported to date, with the largest number of melanomas. The use of fresh frozen AMG has improved the local surgical outcomes by improving healing and reducing scarring as well as allowing for a wider surgical margin.

Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma.

AIM: To present our experience of the use of stereotactic radiosurgery and proton beam therapy to treat posterior uveal melanoma over a 10 year period. METHODS AND MATERIALS: Case notes of patients treated with stereotactic radiosurgery (SRS), or Proton beam therapy (PBT) for posterior uveal melanoma were reviewed. Data collected included visual acuity at presentation and final review, local control rates, globe retention and complications. We analysed post-operative visual outcomes and if visual outcomes varied with proximity to the optic nerve or fovea. RESULTS: 191 patients were included in the study; 85 and 106 patients received Stereotactic radiosurgery and Proton beam therapy, respectively. Mean follow up period was 39 months in the SRS group and 34 months in the PBT group. Both treatments achieved excellent local control rates with eye retention in 98% of the SRS group and 95% in the PBT group. The stereotactic radiosurgery group showed a poorer visual prognosis with 65% losing more than 3 lines of Snellen acuity compared to 45% in the PBT group. 33% of the SRS group and 54% of proton beam patients had a visual acuity of 6/60 or better. CONCLUSIONS: Stereotactic radiosurgery and proton beam therapy are effective treatments for larger choroidal melanomas or tumours unsuitable for plaque radiotherapy. Our results suggest that patients treated with proton beam therapy retain better vision post-operatively; however, possible confounding factors include age, tumour location and systemic co-morbidities. These factors as well as the patient's preference should be considered when deciding between these two therapies.

Failure of intravitreal bevacizumab in the treatment of choroidal metastasis.

BACKGROUND: Metastasis to choroid is the most common intraocular malignancy, arising most frequently from carcinoma of breast in women and lung in men. Recent case reports have described successful use of intravitreal bevacizumab to achieve local control of such tumours. MATERIALS AND METHODS: Five cases of choroidal metastases from varying primaries: breast, lung, and colon were treated with intravitreal bevacizumab, and tumour response observed and documented with serial photographs and B-scans. RESULTS: Four of the five tumours were seen to progress despite intravitreal bevacizumab treatment. CONCLUSIONS: Intravitreal bevacizumab as the primary treatment of choroidal metastases is not recommended and should not delay more effective alternative treatments.

Surpass flow diverter in the treatment of intracranial aneurysms: a prospective multicenter study.

BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study. MATERIALS AND METHODS: At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months. RESULTS: Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at ≤30 days, SAH at ≤7 days, and intraparenchymal hemorrhage at ≤7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%. CONCLUSIONS: Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.

Ocular surface foreign bodies: novel findings mimicking ocular malignant melanoma.

PURPOSE: Malignant melanoma of the eye is an uncommon condition that is important to recognise. We describe three cases in which ocular foreign bodies have masqueraded as ocular malignant melanoma. METHODS: Interventional case reports. RESULTS: Case 1 describes diathermy-induced carbon particle implantation, during plaque therapy for the treatment of uveal melanoma, mimicking recurrence with extra-scleral invasion. Case 2 shows a foreign body called 'mullite' mimicking conjunctival melanoma. Case 3 demonstrates a conjunctival foreign body called 'illite' that mimicked a limbal melanocytic lesion, clinically thought to be either melanocytoma or melanoma. CONCLUSION: This report highlights the importance of careful history taking, examination, and appropriate biopsy in cases of suspected malignant melanoma, to prevent unnecessary and potentially radical treatment.

An internal carotid artery aneurysm presenting with dysarthria.

A 72-year-old woman presented to her general practitioner with a 4-week history of right neck swelling. Clinical examination elicited a pulsatile mass consistent with a carotid artery aneurysm. Five days later the patient noticed her tongue movements had become awkward with associated dysarthria. Computed tomography confirmed a 4cm internal carotid artery aneurysm arising just distally to the carotid bifurcation. She proceeded to transfemoral diagnostic carotid angiography. Balloon occlusion of the right internal carotid artery origin was performed for a ten-minute period without any neurological deficit. The decision was taken to proceed to surgical ligation of the origin of the internal carotid artery. Her symptoms of dysarthria have resolved.

Three cases of intraocular mesectodermal leiomyoma expressing progesterone and androgen receptors.

BACKGROUND/AIMS: A prospective study identified three patients between 2004 and 2010 with mesectodermal leiomyoma. The study was conducted to analyse the presence or absence of sex steroid hormone receptors in mesectodermal leiomyomas. METHODS: The clinical features were collated. All three patients had operative procedures to either remove or sample the mesectodermal leiomyomas. The tissue was fixed in formalin and exposed to conventional histological processing. Immunohistochemistry using antibodies to androgen (AR), oestrogen (ER), and progesterone (PR) receptors was performed, followed by stain scoring to assess for expression status. RESULTS: All three cases were confirmed by histology to be examples of mesectodermal leiomyomas. All three expressed sex steroid hormone receptors. One case expressed both PR and AR, one case PR only and another case AR only. None of the cases expressed ER receptors. CONCLUSION: All three cases displayed some sex steroid hormone receptor expression. This is supportive evidence that sex steroid hormones may have a role in the pathogenesis of this tumour and suggest that it may be amenable to hormonal manipulation therapy, in a manner similar to conventional uterine leiomyomas.

Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia.

Uveal melanoma (UM) is unique among cancers in displaying reduced endogenous levels of sister chromatid exchange (SCE). Here we demonstrate that FANCD2 expression is reduced in UM and that ectopic expression of FANCD2 increased SCE. Similarly, FANCD2-deficient fibroblasts (PD20) derived from Fanconi anaemia patients displayed reduced spontaneous SCE formation relative to their FANCD2-complemented counterparts, suggesting that this observation is not specific to UM. In addition, spontaneous RAD51 foci were reduced in UM and PD20 cells compared with FANCD2-proficient cells. This is consistent with a model where spontaneous SCEs are the end product of endogenous recombination events and implicates FANCD2 in the promotion of recombination-mediated repair of endogenous DNA damage and in SCE formation during normal DNA replication. In both UM and PD20 cells, low SCE was reversed by inhibiting DNA-PKcs (DNA-dependent protein kinase, catalytic subunit). Finally, we demonstrate that both PD20 and UM are sensitive to acetaldehyde, supporting a role for FANCD2 in repair of lesions induced by such endogenous metabolites. Together, these data suggest FANCD2 may promote spontaneous SCE by influencing which double-strand break repair pathway predominates during normal S-phase progression.

Don't it make my blue eyes brown: heterochromia and other abnormalities of the iris.

Eye colour is one of the most important characteristics in determining facial appearance. In this paper I shall discuss the anatomy and genetics of normal eye colour, together with a wide and diverse range of conditions that may produce an alteration in normal iris pigmentation or form.

Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumour of adults, frequently metastasising to the liver. Hepatic metastases are difficult to treat and are mainly unresponsive to chemotherapy. To investigate why UM are so chemo-resistant we explored the effect of interstrand cross-linking agents mitomycin C (MMC) and cisplatin in comparison with hydroxyurea (HU). METHODS: Sensitivity to MMC, cisplatin and HU was tested in established UM cell lines using clonogenic assays. The response of UM to MMC was confirmed in MTT assays using short-term cultures of primary UM. The expression of cytochrome P450 reductase (CYP450R) was analysed by western blotting, and DNA cross-linking was assessed using COMET analysis supported by γ-H2AX foci formation. RESULTS: Both established cell lines and primary cultures of UM were resistant to the cross-linking agent MMC (in each case P<0.001 in Student's t-test compared with controls). In two established UM cell lines, DNA cross-link damage was not induced by MMC (in both cases P<0.05 in Students's t-test compared with damage induced in controls). In all, 6 out of 6 UMs tested displayed reduced expression of the metabolising enzyme CYP450R and transient expression of CYP450R increased MMC sensitivity of UM. CONCLUSION: We suggest that reduced expression of CYP450R is responsible for MMC resistance of UM, through a lack of bioactivation, which can be reversed by complementing UM cell lines with CYP450R.

Retinal vasoproliferative tumours.

Vasoproliferative tumours are uncommon retinal lesions that may occur in isolation (primary) or in association with another ocular condition (secondary). They may be unilateral or bilateral and have a predilection for the peripheral inferior temporal quadrant of the retina. Vasoproliferative tumours can be associated with abnormalities of the macular, including epiretinal membrane formation and cystoid macular edema. A number of modalities have been used to treat these tumours including cryotherapy and radiotherapy.

Conjunctival intra-epithelial neoplasia occurring in young patients with asthma.

BACKGROUND: Conjunctival intra-epithelial neoplasia (CIN) typically occurs in elderly individuals. A number of aetiological factors are implicated in CIN, including life-long exposure to ultra-violet light and immunodeficiency states, particularly HIV infection. Asthma is a common condition affecting more than 3.5 million individuals in the UK, and is associated with atopy in approximately 70% of cases. In this paper we describe CIN occurring in young patients with asthma. METHODS: Retrospective case series: A review of our ocular oncology database helped to identify 11 patients<55 years of age and presenting with CIN. Of these, seven (64%) were noted to have co-existent asthma. RESULTS: Seven patients were included in the study (six male and one female). Mean age at presentation was 44 years (range 36-54 years). Five patients showed unilateral disease, whereas two showed bilateral. Five patients showed local recurrence; however, there were no cases of metastasis. CONCLUSION: The occurrence of CIN, particularly bilateral CIN, in younger immunocompetent individuals is very unusual, and the presence of asthma in 64% of our patient cohort suggests that atopic asthma may be a further aetiological factor involved in the development of this rare neoplasm.

The in vivo modulatory effects of an anterior-chamber microenvironment on uveal melanoma.

BACKGROUND: Primary melanoma of the iris, for reasons unknown has a lower metastatic rate compared with primary ciliary-body melanoma. Six histology cases of ciliary-body melanoma were identified that had spread onto the iris surface and into the stroma, representing a change in tumour microenvironment from aqueous humour non-exposure (ciliary-body component) to aqueous humour exposure (iris surface component). This provided an ideal paradigm for investigating the effects of different environments on melanoma. METHOD: Conventional light microscopy was performed on stained paraffin sections of the identified cases, followed by immunohistochemistry to cell cycle proteins p27 and Cyclin D1. Fluorescence in situ hybridisation (FISH) analysis was conducted on the paraffin sections for changes of chromosomes 3 and 8, associated with poor uveal melanoma prognosis. RESULTS: Iris surface melanoma cells were smaller compared with the adjacent deeper iris stromal melanoma cells and with those in the ciliary body. Fewer iris surface melanoma cells expressed Cyclin D1 protein, but more expressed p27 protein, compared with the larger iris stromal melanoma cells (paired Wilcoxon signed ranks test: Cyclin D1 p = 0.028; p27 p = 0.046) and with the ciliary-body melanoma cells (paired Wilcoxon signed ranks test: Cyclin D1 p = 0.028; p27 p = 0.028). With FISH, chromosome 3 and 8 alterations were less common among the iris surface melanoma cells than the deeper iris stromal melanoma cells and the ciliary-body melanoma cells, which were consistently characterised by a relative genetic imbalance for chromosomes 3 and 8. CONCLUSIONS: These data suggest that there are tumour-modulatory factors within the anterior chamber environment that probably select populations of ciliary-body melanoma cells, with a less aggressive, better-differentiated status. Furthermore, it may help explain why iris melanomas generally have a less aggressive course than ciliary-body and choroidal melanomas.