Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

Is tumour thickness measurement required for MOLES scoring of melanocytic choroidal tumours?

Introduction: It can be challenging to distinguish between choroidal naevi and melanomas in the community setting, particularly without access to ultrasonography, required to measure the thickness of melanocytic choroidal tumours. We aimed to determine whether thickness measurement is required for MOLES scoring of melanocytic choroidal tumours. Methods: The dataset of a recent MOLES evaluation was reviewed. Patients were selected for the present study if their MOLES tumour size category was determined by tumour thickness measured with ultrasonography (US). The largest basal tumour diameter and tumour thickness were then measured from ultra-widefield fundus images and optical coherence tomography (OCT) images, respectively. Results: The tumour size category was determined by tumour diameter in 203/222 (91.4%) with no influence of tumour thickness. The tumour thickness influenced the MOLES score in 19/222 (8.6%) patients. In 11/19 patients with OCT measurements of tumour thickness, the US measurement exceeded the OCT by more than 25% in 5 patients, more than 50% in 2 patients and more than 75% in 1 patient. As a result, the revised tumour thickness based on OCT determined the size category in 4/216 (1.8%) patients. The Optos measurements increased the diameter score by 1 in 5 patients. As a result, the revised tumour thickness determined the size category in 4/216 (1.8%) patients. If both the revised diameter and thickness scores were considered, the MOLES score reduced in 4 patients. If both the diameter and thickness scores were considered, the MOLES score reduced in 5 and increased in 1. Only 0.94% (2/211) of melanocytic choroidal tumours assessed with MOLES when using Optos ultra-widefield fundus images diameter and OCT to measure tumour diameter and thickness, respectively, required a change in management from a reduction in MOLES score from 1 to 0. Discussion/Conclusion: This study suggests that the MOLES category for size is influenced more by the tumour diameter, if it can be measured accurately, than by the thickness. This study suggests ignoring tumour thickness if this cannot be measured accurately with OCT, unless the tumour has a mushroom shape

Survival analysis following enucleation for uveal melanoma

OBJECTIVES: To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. SUBJECTS/METHODS: All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. RESULTS: In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p < 0.001) predicted metastatic mortality on multivariable regression analysis. Those who had an insufficient sample of cells gained during FNAB (n = 16) had no different prognosis. CONCLUSIONS: This study confirms, in this population, the poor survival of patients enucleated for uveal melanomas. It confirms the prognostic utility of adding AJCC grade to cytogenetic information. It demonstrates that the lack of sample in patients undergoing FNAB is not related to prognosis

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21–q24.3, 6p25.1–p21.2, 21q21.2–q21.3 and 21q22.13–q22.3 and loss of 1p36.33–p34.3, 1p31.1–p21.2, 6q16.2–q25.3 and 8p23.3–p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3–p22.3 and 8q23.2–q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM

Isocitrate dehydrogenase 1 mutations (IDH1) and p16/CDKN2A copy number change in conventional chondrosarcomas.

To determine whether IDH1 mutations are present in primary and relapsed (local and distal) conventional central chondrosarcomas; and secondly, to assess if loss of p16/CDKN2A is associated with tumour grade progression, 102 tumour samples from 37 patients, including material from presenting and relapse events, were assessed. All wild-type cases for IDH1 R132 substitutions were also tested for IDH2 R172 and R140 alterations. The primary tumour and the most recent relapse sample were tested for p16/CDKN2A by interphase fluorescence in situ hybridisation. An additional 120 central cartilaginous tumours from different patients were also tested for p16/CDKN2A copy number. The study shows that if an IDH1 mutation were detected in a primary central chondrosarcoma, it is always detected at the time of presentation, and the same mutation is detected in local recurrences and metastatic events. We show that p16/CDKN2A copy number variation occurs subsequent to the IDH1 mutation, and confirm that p16/CDKN2A copy number variation occurs in 75 % of high grade central chondrosarcomas, and not in low grade cartilaginous tumours. Finally, p16/CDKN2A copy number variation is seen in both the IDH1 wild-type and mutant cartilaginous central tumours

Efficacy and timing of adjunctive therapy in the anti-VEGF treatment regimen for macular oedema in retinal vein occlusion:12-month real-world result

PurposeVarious combination treatment regimens have been tried to improve the short-term efficacy of intravitreal monotherapy for the treatment of macular oedema (MO) secondary to retinal vein occlusion (RVO). Our study introduces the RandOL protocol (Ranibizumab and Ozurdex with Laser photocoagulation) of initial anti-VEGF therapy, controlling recurrent non-ischaemic MO with an intravitreal steroid and applying laser therapy to non-perfused retina. We describe our 12-month follow-up experience on timing for adjunctive therapy and real-world effectiveness and safety data.MethodsA retrospective analysis was carried out on 66 consecutive treatment-naive RVO patients with MO who received our RandOL treatment regimen. Baseline visual acuity (VA) and central retinal thickness (CRT) were compared with 12-month result.ResultsAt 12 months, 77% had significant VA improvement, 52% had ≥3-line improvement, and 15% were worse. Significant improvements in CRT were observed in 97% (baseline median CRT=531 μm (IQR 435-622) reduced to 245 μm (IQR 221-351, P<0.001) at 12 months); 76% achieved a dry fovea at 1 year. Mean number of total injections required was 5.5 (range 2-11) and 6% required ≥9 injections in 1 year. Although 70% received additional Ozurdex, 82% received ≥1 sessions of laser therapy. The BRVO subgroup achieved better VA and CRT improvement at 1 year, but small numbers limit definitive statistical conclusions.ConclusionsOur real-world results using a combination treatment protocol for RVO-related MO achieved similar desirable anatomical and visual outcomes as with a single-agent therapy with less intravitreal re-treatment rates at first year. Randomised controlled studies are needed to evaluate the role of laser and the ideal timing of combination therapy

“Multidimensional child sex rings”: a systematic review of the literature

Background: In 1983 Kennet Lanning began his studies dealing with sexual rituals, and in 1985 there calls “Multidimensional Child Sex Rings” identifying features and modes (Lanning, 1992). In his studies Lanning (1992), describes the types of offences related to the dimension of ritual abuse by claiming that there is no clear evidence about some of these crimes. On the basis of those statements Weir and Wheatcroft (1995) list as possible by declaring a false ritual abuse and then of false memories, the suggestion of special interest about the growing psychotherapists induced ritual abuse and who believe in the existence of these crimes.This systematic review of the literature, in the light of subsequent events and subsequent updates of methodology aims to analyze the relationship between “Ritual Abuse” and the false memory that can appear during psychotherapy. Materials and Methods: This study was carried out using the PRISMA guidelines, by conducting a systematic search of the literature on PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar, and ScienceDirect. The following keywords used were “ritual abuse” “AND” (i.e., Boolean operator) “psychotherapy” combined with “AND” Boolean operator and “false memory”.Results: The initial search identified n = 167 citations. Only one research report met the predefined inclusion criteria and was analysed.Conclusion: In case of false memories in ritual abuse, it is necessary to implement the research activities to avoid that results obtained can be rejected by health professionals or by theories not scientifically validated.Background: Nel 1983 Kennet Lanning inizia i suoi studi occupandosi di abusi sessuali rituali, e nel 1985 lì definisce “Multidimensional Child Sex Rings” identificandone caratteristiche e modalità (Lanning, 1992). Nei suoi studi Lanning (1992), descrive le tipologie di reato connesse alla dimensione dell’abuso rituale sostenendo che non esistono prove certe in merito ad alcuni di questi reati. Sulla base di tali affermazioni Weir and Wheatcroft (1995) elencano come possibili ipotesi di generazione di falsi abusi rituali e quindi di falsi ricordi, la suggestione indotta di psicoterapeuti che coltivano speciali interessi circa gli abusi rituali e che credono nell’esistenza di questi crimini. La presente analisi sistematica della letteratura, alla luce dei successivi accadimenti e di successivi aggiornamenti metodologici ha lo scopo di analizzare la relazione tra “Abuso Rituale” ed il falso ricordo che può manifestarsi durante la psicoterapia. Materiali e Metodi: Tale studio è stato effettuato utilizzando le linee guida per l’utilizzo della metodología PRISMA, effettuando una ricerca sistematica su PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar e ScienceDirect. Le parole chiave utilizzate per la ricerca sono state “ritual abuse” “AND” (i.e. operatore Boleano) “psychotherapy” “AND” “false memory”.Risultati: Sono stati inizialmente trovati n = 167 records. Un solo articolo ha poi soddisfatto i criteri di inclusione ed è stato analizzati.Conclusioni: Nel caso delle false memorie negli abusi rituali, sembra necessario implementare l’attività di ricerca per evitare che qualsiasi risultato ottenuto possa essere contrastato dai professionisti della salute o da teorie non validate scientificamente

Long-term visual outcomes after ruthenium plaque brachytherapy for posterior choroidal melanoma

BACKGROUND: To assess the long-term visual outcomes in patients with posteriorly located choroidal melanoma treated with ruthenium plaque brachytherapy between January 2013 and December 2015. METHODS: A retrospective review was conducted on consecutive patients treated with ruthenium plaque brachytherapy for post-equatorial choroidal melanoma with available Snellen visual acuity before and after treatment, and the development and treatment of radiation complications. RESULTS: There were 219 patients with posterior choroidal melanoma treated with ruthenium plaque brachytherapy. Median follow up was 56.5 months, range 12-81 months. Final visual acuity was ≥6/12 in 97 (44.3%) patients, 6/12 to 6/60 in 57 (26.0%), <6/60 in 55 (25.1%) and 10 (4.6%) eyes were enucleated. Radiation maculopathy was the most common radiation complication encountered, occurring in 53 (24.2%) patients. Of these, final visual acuity was 6/12 in 10 patients (18.9%), 6/12 to 6/60 in 26 (49.1%), <6/60 in 16 (30.2%) and 1 eye (1.9%) was enucleated. Twenty-five (47%) with radiation maculopathy were treated with intravitreal anti-angiogenic therapy, 27 (51%) were monitored and one (2%) was treated with scatter photocoagulation. Eyes treated with intravitreal anti-angiogenic therapy had better final vision than those observed or treated with retinal laser (chi-square, p = 0.04). On multivariate analysis, close proximity to the optic nerve and fovea, and large or notched plaque type was associated with final vision worse than 6/12. CONCLUSION: Most patients treated with ruthenium plaque brachytherapy for posterior choroidal melanoma retain 6/60 vision, with almost half retaining 6/12 vision at long term follow up

Uveal melanoma UK national guidelines

The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website