Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

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.

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.

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.

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.

Management of symptomatic choroidal naevi with photodynamic therapy.

BACKGROUND/AIMS: To describe the use of photodynamic therapy (PDT) in the management of symptomatic serous retinal detachment associated with choroidal naevi. METHODS: Interventional case series. The records of seven patients with choroidal naevus and associated serous retinal detachment, treated with PDT were reviewed retrospectively. Main outcome measures were Snellen visual acuity, clinical appearance, and ocular tomographic findings. RESULTS: All seven patients showed a reduction in the degree of serous detachment and symptomatic improvement. Five patients showed a corresponding improvement in visual acuity that persisted over a mean period of 9 months. CONCLUSION: PDT appears to be effective in the management of serous retinal detachment associated with choroidal naevus.

Proton beam therapy for iris melanoma: a review of 15 cases.

AIM: To report results of proton beam therapy for iris melanoma. METHODS: A retrospective case series of 15 patients with nonresectable iris melanomas treated with proton beam therapy between August 1998 and August 2004. The main outcome measures were (1) local tumour control, (2) complications, and (3) eye retention. RESULTS: Of the 15 cases, 11 patients showed documented growth (including two cases of local recurrence following iridocyclectomy) while a further three cases were biopsy-proven melanoma. One patient presented with a newly acquired vascular nodule of the iris associated with angle seeding and glaucoma. Tumour control at mean follow-up of 34 months was 93% (14 of 15 eyes). Common complications included glaucoma in 53% (five patients had glaucoma prior to irradiation), dry eye (27%) and cataract in three patients (20%). Eye retention was possible in 80% (12 cases). CONCLUSION: Proton beam therapy is an effective treatment for cases of nonresectable iris melanoma. The major complications are cataract and glaucoma.

Bovine pericardium (Tutopatch) wrap for hydroxyapatite implants.

PURPOSE: To evaluate bovine pericardium (Tutopatch) as a wrapping material for hydroxyapatite implants in patients undergoing enucleation for uveal melanoma. METHOD: Prospective cohort study of patients who had enucleation for uveal melanoma between January 2003 and August 2003 were included in the study. Any patient with less than 3 months follow-up was excluded. Enucleation was performed under general anaesthesia followed by insertion of hydroxyapatite implants wrapped in bovine pericardium (Tutopatch). The recti muscles were sutured directly to the wrap. The tenon's capsule and conjunctiva were closed in two layers. A conformer was inserted at 1 week and artificial eye at 2-3 months. The patients were followed up regularly and were assessed for cosmetic result, exposure of implant, and the need for any further surgical procedures. RESULTS: A total of 19 patients (seven male and 12 female) were included in the study. Median age at diagnosis was 63 years (range 38-80 years). Median follow-up was 26 months (range 22-30 months). No patient developed postoperative complications of wound dehiscence. The overall cosmetic result was excellent in all the patients. The rate of postoperative complications compared favourably with published data using other wrapping materials/implants. CONCLUSION: Tutopatch is a safe wrapping material for hydroxyapatite orbital implants in patients undergoing enucleation for uveal melanoma.

A simulation-based approach to forecasting the next great San Francisco earthquake.

In 1906 the great San Francisco earthquake and fire destroyed much of the city. As we approach the 100-year anniversary of that event, a critical concern is the hazard posed by another such earthquake. In this article, we examine the assumptions presently used to compute the probability of occurrence of these earthquakes. We also present the results of a numerical simulation of interacting faults on the San Andreas system. Called Virtual California, this simulation can be used to compute the times, locations, and magnitudes of simulated earthquakes on the San Andreas fault in the vicinity of San Francisco. Of particular importance are results for the statistical distribution of recurrence times between great earthquakes, results that are difficult or impossible to obtain from a purely field-based approach.