Paul Rundle

Photodynamic therapy of circumscribed choroidal haemangioma

Aim: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma. Design: Prospective non-randomised, interventional case series and critical review of previously published studies. Methods: 10 consecutive patients (seven primary, two failed transpupillary thermotherapy (TTT), and one failed external beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10 minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50 J/cm2) was applied 5 minutes after completion of infusion. Single or multiple partially overlapping spots were applied based on the tumour basal dimensions. Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. Results: All 10 patients showed evidence of regression with flattening of tumour, resolution of subretinal fluid, and reduction of choroidal vasculature on angiograms. The visual acuity either improved or remained stable in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in two patients. Conclusions: Although verteporfin PDT is an effective treatment for management of symptomatic circumscribed choroidal haemangioma, delayed treatment related effects can lead to visual loss.

A critical appraisal of the prognostic and predictive factors for uveal malignant melanoma

The intraocular uveal tract comprises the iris, ciliary body and choroid. It contains a well-characterized population of melanocytes, from which uveal malignant melanoma takes origin. In adults uveal melanoma is the commonest primary intraocular malignant tumour. The estimated annual incidence ranges from 7.9 cases per million per year in the USA to 10 cases per million per year in Europe. Uveal melanoma is commoner in Caucasian males, with a median age of presentation of around 60 years. The incidence amongst whites is eight times greater than in blacks. The cause of uveal malignant melanoma is unknown, but several risk factors have been associated with disease development. Some personal characteristics, such as fair complexion, light irides, uveal naevi, dysplastic naevus syndrome, oculodermal and ocular melanocytosis and neurofibromatosis type 1 (NF1) have been associated with an increased risk of uveal melanoma. Furthermore, familial uveal melanoma is recognized and accounts for 0.6% of all uveal melanoma cases, with a proposed autosomal dominant mode of inheritance. The mortality due to uveal melanoma has remained relatively unchanged, despite earlier detection and consequently smaller primary tumour burdens. Metastasis occurs via the blood, classically to the liver, and around 1% of patients have clinically demonstrable liver metastases at presentation. Ultimately, 40% of patients will go on to develop liver metastases, which occur, on average, 10 years after diagnosis and treatment of the primary neoplasm. This probably reflects subclinical hepatic metastasis at the time of the initial diagnosis. Once liver metastases are clinically apparent, the outlook is poor (survival on average 5–9 months).

Survival and complications following Gamma Knife radiosurgery or enucleation for ocular melanoma: a 20-year experience

BackgroundWe present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20xa0years.MethodWe analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70xa0Gy for 24 patients, 45xa0Gy for 71 patients, 35xa0Gy for 62 patients.FindingsThere was no significant difference in survival between the 35-Gy, 45-Gy and 50– to 70-Gy groups when compared between themselves (pu2009=u20090.168) and with the enucleation group (pu2009=u20090.454). The 5-year survival rates were: 64% for 35xa0Gy, 62.71% for 45xa0Gy, 63.6% for 50–70xa0Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (pu2009=u20090.014) and location (median 66.4 vs 37.36xa0months for juxtapapillary vs peripheral tumours, respectively; pu2009=u20090.001), while age and gender did not prove significant. Regarding complications, using 35xa0Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45xa0Gy to 31.4% for 35xa0Gy (pu2009=u20090.006), as well as post-radiosurgery enucleation: 23.9% for 45xa0Gy vs 6.45% for 35xa0Gy (pu2009=u20090.018). Visual acuity, recorded up to 5xa0years post-radiosurgery, was significantly better preserved for 35xa0Gy than for 45xa0Gy (pu2009=u20090.0003).ConclusionsUsing 35xa0Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

Ocular surface squamous neoplasia: analysis of 78 cases from a UK ocular oncology centre

Background/aims Ocular surface squamous neoplasia (OSSN) is a spectrum of disease, on which few large series have been published, none in particular, from the UK. The purpose of this study is to describe experience of this condition from a UK national ocular oncology centre, including statistical analysis to elucidate factors significant in recurrence. Methods Retrospective review of case notes, clinical photographs and histopathology reports. Results 78 cases were included, of which 10 (12.8%) recurred during the follow-up time (mean 37u2005months). The 1-year recurrence rate was 10.9%, and 5-year recurrence rate was 18.5% using Kaplan-Meier analysis, with a mean time to recurrence of 9.5u2005months. Significant factors in recurrence were tumour size and first treatment given. Grade of OSSN, including presence of invasive disease and positive biopsy margins were not found to be statistically significant in recurrence. Conclusions OSSN in an uncommon disease in the UK population. However, when managed appropriately in a specialist centre, it is associated with good outcomes, even in recurrence situations.

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 pu200a=u200a0.028; p27 pu200a=u200a0.046) and with the ciliary-body melanoma cells (paired Wilcoxon signed ranks test: Cyclin D1 pu200a=u200a0.028; p27 pu200a=u200a0.028). 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.

Congenital hypertrophy of retinal pigment epithelium: a clinico-pathological case report

Congenital hypertrophy of retinal pigment epithelium (CHRPE) is a peculiar congenital anomaly of the retinal pigment epithelium (RPE) diagnosed by its characteristic ophthalmoscopic appearance.1 It is now realised that sporadic CHRPE is distinct from the similar appearing retinal lesions described in patients with Gardner’s syndrome.2–4 We recently enucleated an eye with a choroidal melanoma that also had a distinct area of solitary CHRPE with lacunae formation. This provided us with a unique opportunity to correlate clinical and histopathological features of a solitary CHRPE.nnA 62 year old woman with a large cilio-choroidal melanoma was observed to have an elliptical retinal pigment epithelial lesion about 1 mm temporal to the foveola (fig 1A). The lesion was about 3 mm×2 mm in basal dimension and appeared flat. The lesion was depigmented in the nasal aspect with scalloped hyperpigmentation temporally. The eye was enucleated and processed routinely for histological examination.nnnn Figure 1 nu2003(A) Fundus photograph of the left eye showing an elliptical area of congenital retinal pigment epithelial (RPE) lesion temporal …

Adenoma of ciliary pigment epithelium: a case series

Adenoma of ciliary pigment epithelium is a rare tumour. Many are diagnosed retrospectively either after excision or enucleation, as malignant melanoma is suspected.1 We report a series of four patients found to have adenoma of ciliary pigment epithelium and discuss the clinical features and unusual behaviour of these neoplasms.nnWe reviewed the histopathological reports in the ophthalmic pathology archive dating from 1980 to date and identified four patients who had the histopathological diagnosis of adenoma of ciliary pigment epithelium. We crosschecked the details with the clinical oncology database. We reviewed their notes for features that would help us to identify this ciliary body tumour clinically. The salient features of these patients are given in Table 1.nnView this table:nn Table 1 nClinical details of the patients with adenoma of the pigment epithelium of ciliary bodynnnnPatient 1 was reported elsewhere in 1994.2 He had a dark brown multinodular mass in the inferotemporal anterior chamber angle of the left eye. His tumour was a relatively small but invasive lesion. Patient 2 was the only non-white patient with this condition in our series. Her tumour was an incidental finding when she presented to an ophthalmologist with allergic conjunctivitis. The tumour was small and dark brown. The tumour had invaded the anterior chamber angle and the root of the iris occupying one clock hour of the angle (Fig 1A, B, and C). Adenoma of the ciliary body was suspected, as she was non-white and the degree of anterior chamber invasion appeared disproportionate to the size of the tumour.nnnn Figure 1 n(A) A small ciliary body adenoma invading the …

Bovine pericardium (Ocuguard) wrap for hydroxyapatite implants

Hydroxyapatite implant becomes vascularised and integrated in the orbital tissues. In view of the rough hard external surface, wrapping materials are used to enclose the hydroxyapatite implant that facilitate attachment of extraocular muscles. Various wrapping materials have been tried including donor human sclera,1 acellular dermis,2 rectus abdominis sheath,3 posterior auricular muscle,4 polyglactin mesh,5 and bovine pericardium.6 In this report, we present our 5 year experience with the use bovine pericardium wrap. The wrap is presterilised using glutaraldehyde, ethanol, and propylene oxide to minimise the risk of transmission of bacterial and viral infections.nnAll patients undergoing primary enucleation for large choroidal melanoma with the insertion of hydroxyapatite implant wrapped in processed bovine pericardium were included in the study. Patients with less than 3 months’ postoperative follow up or radiotherapy …

Uveal MALT lymphoma with extensive AL‐type amyloid production mimicking uveal melanoma

zetto M. Interferon treatment for multiple sclerosis: autoimmune complications may be lethal. Neurology 1998; 50; 570–571. 4. Pietrosi G, Mandala L, Vizzini GB et al. Fulminant hepatic failure and autoimmune disorders in patient with multiple sclerosis on interferon beta 1a: a fatal combination? Transpl. Int. 2008; 21; 502–504. 5. Wallack EM, Callon R. Liver injury associated with the beta-interferons for MS. Neurology 2004; 63; 1142–1143. 6. Yoshida EM, Rasmussen SL, Steinbrecher UP et al. Fulminant liver failure during interferon beta treatment of multiple sclerosis. Neurology 2001; 56; 1416.

Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential

PURPOSEnUveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi.nnnDESIGNnMulticenter, retrospective case series.nnnPARTICIPANTSnPatients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment.nnnMETHODSnNext-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples.nnnMAIN OUTCOME MEASURESnMutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis.nnnRESULTSnIn 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi.nnnCONCLUSIONSnMutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of BAP1 expression as seen in choroidal melanoma. Consequently, iris melanoma is a distinct molecular subgroup of UM. Histologic borderline malignant iris nevixa0can harbor BAP1 mutations and may be designated iris melanocytic tumors of uncertain malignant potential.