Outcome Measures of New Technologies in Uveal Melanoma: Review from the European Vision Institute Special Interest Focus Group Meeting.

Uveal Melanoma (UM) is the most common primary intra-ocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "Outcome Measures of New Technologies in Uveal Melanoma", addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient's wellbeing. This review highlights the meeting's presentations in the context of the published literature.

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Porous Versus Nonporous Orbital Implants After Enucleation for Uveal Melanoma: A Randomized Study.

PURPOSE: To compare hydroxyapatite with acrylic implants after enucleation for uveal melanoma with respect to eyelid position, ocular motility, implant complications, and patient satisfaction. METHODS: Patients undergoing primary enucleation for uveal melanoma between May 2005 and November 2012 at the Liverpool Ocular Oncology Centre, United Kingdom, were randomized between hydroxyapatite and acrylic implants. Questionnaires were sent to patients and ocularists to comment on the main outcomes. RESULTS: A total of 416 patients were recruited in the study, of whom 281 were included, with 49.5% (139/281) and 50.5% (142/281) receiving a hydroxyapatite (HA) or acrylic (AC) implant. Mailed questionnaires completed at ≥18 months by patients showed no significant differences between the groups in eyelid position, prosthetic motility, socket complications, and patient satisfaction. Complications included implant extrusion (1% vs 4%), enophthalmos (26% vs 26%), and superior sulcus deformity (24% vs 24%) with HA and AC implants, respectively, (Fisher exact test p > 0.0125 in all, Bonferroni correction). Questionnaires completed by ocularists indicated no significant differences in eyelid opening, prosthetic motility, and other complications at 6 months (Fisher exact test, p > 0.05 in all); there was a higher prevalence of ptosis with AC than HA implants (46% vs 25%, p = 0.03) and a greater need for ocularists' treatment with HA than AC (50% vs 28%, p = 0.03). CONCLUSIONS: Patient-reported outcomes after enucleation for uveal melanoma indicate no major differences between hydroxyapatite and acrylic implants in surgical outcomes and patient satisfaction. There was a higher prevalence of ptosis with AC and a greater need of ocularists' visits with HA at around 6 months observed by ocularists.

Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma.

PURPOSE: To determine underlying correlations in multiplex ligation-dependent probe amplification (MLPA) data and their significance regarding survival following treatment of choroidal melanoma (CM). METHODS: MLPA data were available for 31 loci across four chromosomes (1p, 3, 6, and 8) in tumor material obtained from 602 patients with CM treated at the Liverpool Ocular Oncology Center (LOOC) between 1993 and 2012. Data representing chromosomes 3 and 8q were analyzed in depth since their association with CM patient survival is well-known. Unsupervised k-means cluster analysis was performed to detect latent structure in the data set. Principal component analysis (PCA) was also performed to determine the intrinsic dimensionality of the data. Survival analyses of the identified clusters were performed using Kaplan-Meier (KM) and log-rank statistical tests. Correlation with largest basal tumor diameter (LTD) was investigated. RESULTS: Chromosome 3: A two-cluster (bimodal) solution was found in chromosome 3, characterized by centroids at unilaterally normal probe values and unilateral deletion. There was a large, significant difference in the survival characteristics of the two clusters (log-rank, p<0.001; 5-year survival: 80% versus 40%). Both clusters had a broad distribution in LTD, although larger tumors were characteristically in the poorer outcome group (Mann-Whitney, p<0.001). Threshold values of 0.85 for deletion and 1.15 for gain optimized the classification of the clusters. PCA showed that the first principal component (PC1) contained more than 80% of the data set variance and all of the bimodality, with uniform coefficients (0.28±0.03). Chromosome 8q: No clusters were found in chromosome 8q. Using a conventional threshold-based definition of 8q gain, and in conjunction with the chromosome 3 clusters, three prognostic groups were identified: chromosomes 3 and 8q both normal, either chromosome 3 or 8q abnormal, and both chromosomes 3 and 8q abnormal. KM analysis showed 5-year survival figures of approximately 97%, 80%, and 30% for these prognostic groups, respectively (log-rank, p<0.001). All MLPA probes within both chromosomes were significantly correlated with each other (Spearman, p<0.001). CONCLUSIONS: Within chromosome 3, the strong correlation between the MLPA variables and the uniform coefficients from the PCA indicates a lack of evidence for a signature gene that might account for the bimodality we observed. We hypothesize that the two clusters we found correspond to binary underlying states of complete monosomy or disomy 3 and that these states are sampled by the complete ensemble of probes. Consequently, we would expect a similar pattern to emerge in higher-resolution MLPA data sets. LTD may be a significant confounding factor. Considering chromosome 8q, we found that chromosome 3 cluster membership and 8q gain as traditionally defined have an indistinguishable impact on patient outcome.

Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival.

Metastatic death from uveal melanoma occurs almost exclusively with tumors showing monosomy of chromosome 3. However, approximately 5% of patients with a disomy 3 uveal melanoma develop metastases, and a further 5% of monosomy 3 uveal melanoma patients exhibit disease-free survival for >5 years. In the present study, whole-genome microarrays were used to interrogate four clinically well-defined subgroups of uveal melanoma: i) disomy 3 uveal melanoma with long-term survival; ii) metastasizing monosomy 3 uveal melanoma; iii) metastasizing disomy 3 uveal melanoma; and iv) monosomy 3 uveal melanoma with long-term survival. Cox regression and Kaplan-Meier survival analysis identified that amplification of the CNKSR3 gene (log-rank, P = 0.022) with an associated increase in its protein expression (log-rank, P = 0.011) correlated with longer patient survival. Although little is known about CNKSR3, the correlation of protein expression with increased survival suggests a biological function in uveal melanoma, possibly working to limit metastatic progression of monosomy 3 uveal melanoma cells.

Vitreoretinal surgery for complications of choroidal tumor biopsy.

OBJECTIVE: To determine the outcomes of vitreoretinal surgery after choroidal tumor biopsy. DESIGN: Retrospective, single-center, consecutive case series. PARTICIPANTS: A total of 739 consecutive patients undergoing choroidal tumor biopsy. METHODS: All subjects who underwent transretinal or transscleral choroidal tumor biopsy for diagnostic or prognostic purposes between May 1993 and May 2013 were identified in our database. We then reviewed patients who subsequently required secondary vitreoretinal surgery for complications arising from such biopsies. MAIN OUTCOME MEASURES: Reason for vitreoretinal surgery, association with biopsy procedure, best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR]), intraocular or extrascleral tumor dissemination, resolution of vitreous hemorrhage, reattachment of the retina with a single vitreoretinal procedure, number of additional vitrectomies undertaken, and number of enucleations. RESULTS: A total of 20 of 739 eyes (2.7%) underwent vitreoretinal surgery for complications arising from choroidal tumor biopsy. The tumors consisted of choroidal melanoma in all 20 eyes. The reasons for the secondary surgery included persistent vitreous hemorrhage in 1.9% (14/739), rhegmatogenous retinal detachment in 0.7% (5/739), and endophthalmitis in 0.14% (1/739). Median BCVA improved from 2.0 logMAR (mean, 1.92 logMAR; range, 0.8-2.7 logMAR) before vitrectomy to 0.72 logMAR (mean, 0.88 logMAR; range, -0.14 to 2.7 logMAR) after vitrectomy and 0.76 logMAR (mean, 1.14 logMAR; range, 0.1-3.0 logMAR) at the final visit (P < 0.0001, t test). Permanent resolution of vitreous hemorrhage was achieved in 6 of 14 patients, and reattachment of the retina was achieved in 2 of 5 patients after the first vitrectomy. A median of 1 (mean, 1.5; range, 1-3) additional vitrectomy was performed. Enucleation was necessary in 3 of 20 eyes (15%). There were no cases of intraocular invasion or extrascleral extension after vitrectomy. CONCLUSIONS: Vitrectomy for complications of choroidal tumor biopsy is rare. Such corrective surgery is complex and is best undertaken by specialized ocular oncologists or vitreoretinal surgeons with experience in managing this problem.

Assessment of Remote Training, At-Home Testing, and Test-Retest Variability of a Novel Test for Clustered Virtual Reality Perimetry.

OBJECTIVE: To assess the feasibility of remotely training glaucoma patients to take a 10-session clustered virtual reality (VR) visual field (VF) test (Vivid Vision Perimetry [VVP-10]) at home, analyze results for test-retest variability, and assess correspondence with conventional perimetry. DESIGN: Cross-sectional study. SUBJECTS: Twenty-one subjects with glaucoma were enrolled and included in the feasibility assessment of remote training. Thirty-six eyes were used for test-retest analysis and determination of concordance with the Humphrey Field Analyzer (HFA). METHODS: Subjects were provided with a mobile VR headset containing the VVP-10 test software and trained remotely via video conferencing. Subjects were instructed to complete 10 sessions over a 14-day period. MAIN OUTCOME MEASURES: Feasibility was determined by the number of subjects who were able to independently complete VVP-10 over the 14-day period after 1 remote training session. The intraclass correlation coefficient (ICC) for average fraction seen across 10 sessions and the standard error (SE) of the mean were primary outcome measures for assessing test-retest variability. Correlation with HFA mean sensitivity (MS) across eyes, was a secondary outcome measure. RESULTS: Twenty subjects (95%) successfully completed the VVP-10 test series after 1 training session. The ICC for VVP-10 was 0.95 (95% confidence interval [CI], 0.92-0.97). The mean SE in units of fraction seen was 0.012. The Spearman correlations between VVP-10 average fraction seen and HFA MS were 0.87 (95% CI, 0.66-0.98) for moderate-to-advanced glaucoma eyes, and decreased to 0.67 (95% CI, 0.28-0.94) when all eyes were included. CONCLUSIONS: Remote training of patients at home is feasible, and subsequent remote clustered VF testing using VVP-10 by patients on their own, without any further interactions with caregivers or study staff, was possible. At-home VVP-10 results demonstrated low test-retest variability. Future studies must be conducted to determine if VVP-10, taken at home as convenient for the patient, may be a viable supplement to provide equivalent or complementary results to that of standard in-clinic assessment of visual function in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Intraocular collision tumour: case report and literature review.

BACKGROUND: "Collision" tumours consist of different neoplasms coexisting within a single lesion. Whilst quite common in the skin, the gastrointestional tract, and the ovaries, intraocular collision tumours are exceedingly rare. We describe an exceptional case of a combined uveal melanoma and intraocular plasmacytoma. METHODS: Observational case report. A 61-year-old woman underwent enucleation for rubeotic glaucoma and cells in the anterior chamber after proton-beam radiotherapy of a cilio-choroidal melanoma of the right eye. Examination of the enucleated eye was performed with immunohistochemistry, multiplex ligation dependent probe amplification (MLPA), and polymerase chain reaction (PCR) for immunoglobulin heavy- and light-chain gene rearrangements. A review of the literature on ocular collision tumours and uveal involvement by plasma cell neoplasms was also performed. RESULTS: Morphological, immunophenotypical, and genotypical examination of the tumour revealed the co-existence of both a melanoma and a plasmacytoma within the choroid and ciliary body. The glaucoma was caused by extensive infiltration of the iris and trabecular meshwork by the plasmacytoma cells. Review of the literature revealed only four collision tumours involving the eyelid and three involving the choroid. All three intraocular collision tumours consisted of uveal melanoma and choroidal non-Hodgkin lymphoma. Uveal involvement by plasma cell neoplasms is also extremely rare, with only six reported cases. CONCLUSIONS: This is the first documented intraocular collision tumour consisting of a uveal melanoma and isolated plasmacytoma. If a patient presents with 'uveitis' after proton-beam radiotherapy of a cilio-choroidal melanoma, there may be scope for performing biopsies to determine whether the lymphoid infiltrate is reactive or neoplastic.

Can the MOLES acronym and scoring system improve the management of patients with melanocytic choroidal tumours?

It can be difficult for practitioners to determine the likelihood of malignancy in melanocytic choroidal tumours. This author has therefore devised the MOLES acronym to highlight the most informative clinical features, which comprise mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. Each of these is scored 0 if absent, 1 if subtle or uncertain, and 2 if present. Tumours are categorised as 'common naevus', 'low-risk naevus', 'high-risk naevus' and 'probable melanoma' according to whether the sum of these five scores is 0, 1, 2 or 3 or more, respectively. Tentative recommendations, subject to future studies, include: review of 'common naevi' by a community optometrist whenever the patient attends for another reason, such as a two-yearly 'check-up' (i.e., 'self-care'); non-urgent referral of patients with 'low-risk naevi' or 'high-risk naevi' to an ophthalmologist to plan long-term surveillance (i.e., determining the frequency of assessments and whether these should be undertaken by an ophthalmologist or a community optometrist); and urgent referral of patients with a MOLES score >2 (i.e., 'probable melanoma') to an ophthalmologist for immediate referral to an ocular oncologist if a suspicion of malignancy is confirmed. The MOLES system does not require assessment of internal acoustic reflectivity by ultrasonography. MOLES scores correlate well with diagnosis of choroidal naevi and melanomas by ocular oncologists; however, further evaluation of this aid in routine optometric practice and other situations is needed. MOLES should prevent unnecessary referral of patients with naevi for second opinion and non-essential monitoring of these patients at hospital eye services.

Adenoma of the nonpigmented ciliary epithelium presenting as glaucoma.

Purpose: We describe a case of adenoma of the nonpigmented ciliary epithelium in a 58-year-old male, who presented with glaucoma. Observations: A healthy White male was incidentally found to have an elevated intraocular pressure in his left eye (25 mmHg) during a visit to a local optometrist. After further investigations he was diagnosed with a primary open angle glaucoma (POAG) and treated with drops for two years until he developed a sectorial cataract. During the first dilated eye exam, a pale tan tumor was discovered, that seemed to originate from the superior ciliary body, causing a sectorial-cortical cataract and subluxation of the lens. The eye was enucleated on the suspicion of a rare adult medulloepithelioma, because of multicystic features on B-scan ultrasonography. However, histopathological examination revealed an adenoma of the nonpigmented ciliary epithelium that grew in trabecular papillary patterns, with smaller areas of solid and microcystoid growth. As this is a benign tumor without metastatic potential, the patient was referred back to his home clinic without requirement for radiological staging or screening. Conclusion and Importance: Adenomas of the nonpigmented ciliary epithelium (NPCE adenomas) are benign tumors that are often mistaken for malignant counterparts. Thus, this case report expands on the available literature of this rare entity.

The MOLES system to guide the management of melanocytic choroidal tumours: can optometrists apply it?

CLINICAL RELEVANCE: Although melanocytic choroidal tumours of the choroid are a common eye pathology, no standardised protocol exists for their management in the community. BACKGROUND: Choroidal naevi are found in approximately 6% of the adult White population, whereas choroidal melanomas are rare, with an annual incidence of 5-10/million/year. Multimodal imaging has advanced the understanding of malignancy imaging biomarkers, but distinguishing between a small melanoma and naevus remains difficult and an algorithm for their management by community practitioners has not been uniformly adopted. One of the authors (BD) devised the MOLES scoring system, which indicates malignancy likelihood according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. When applied by ocular oncologists, the system accurately distinguishes choroidal naevi from melanomas. The aim of this study was to evaluate whether community optometrists can appropriately manage patients with melanocytic choroidal tumours using this system. METHODS: Clinical images of 25 melanocytic choroidal tumours were presented in an online survey, including colour fundus photographs, fundus autofluorescence, optical coherence tomography, and B-scan ultrasound images. Using the MOLES system, 39 optometrists diagnosed tumours as naevus or probable melanoma and decided between community monitoring and ophthalmologist referral. Responses were compared to MOLES grading of the same clinical images by ocular oncologists. RESULTS: Using MOLES, optometrists correctly identified 389/406 probable melanomas (95.8% sensitivity) and 331/516 choroidal naevi (64.1% specificity); correctly referred 773/778 tumours to an ophthalmologist (99.4% sensitivity); and correctly managed 80/144 lesions (55.6% specificity) in the community. CONCLUSION: Optometrists safely applied the MOLES scoring system in this survey. Further measures are indicated to reduce choroidal naevi over-referral and evaluate MOLES system usage in clinical optometric practice, where some imaging modalities may not be readily available.

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.

Detection and time to treatment of uveal melanoma in the United Kingdom: an evaluation of 2,384 patients.

PURPOSE: To determine the mode of detection of uveal melanoma and time to treatment in the United Kingdom. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 2384 patients diagnosed with uveal melanoma at the Liverpool Ocular Oncology Center between 1996 and early 2011. METHODS: A questionnaire was completed with every new patient, and the results were correlated with clinical features and treatment. MAIN OUTCOME MEASURES: Tumor detection, practitioner initiating referral, referral pathway, time to treatment, baseline clinical features, and primary ocular treatment. RESULTS: The referral process was initiated by an optometrist, family doctor, or ophthalmologist in 68.0%, 18.2%, and 13.8% of patients, respectively. On referral, 30.2% of patients were asymptomatic. Twenty-three percent of patients reported that their tumor was initially missed; these tended to have a more advanced tumor when they reached our center. The time from referral to treatment had a median of 49 days, exceeding 6 months in 19.8% of patients. This delay was longer in patients who reported that their tumor was missed (median, 92 vs. 40 days; Mann-Whitney, P<0.001). Ophthalmologists delayed the referral process by more than 6 months in 10.9% of patients. Primary enucleation was performed in 33.3% of patients and was more likely in those who reported that their tumor was missed (44.8% vs. 29.8%; chi-square, P<0.001). CONCLUSIONS: Many patients with uveal melanoma experience long delays in treatment because their tumor was missed or misdiagnosed. Such patients tend to have a more advanced tumor by the time they reach an oncology center and are more likely to require enucleation.

Proteomic analyses of the vitreous humour.

The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. In the last decade, proteomics analyses have been performed to characterise the proteome of the human VH and explore networks of functionally related proteins, providing insight into the aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent proteomic studies on the VH from animal models of autoimmune uveitis have identified new signalling pathways associated to autoimmune triggers and intravitreal inflammation. This paper aims to guide biological scientists through the different proteomic techniques that have been used to analyse the VH and present future perspectives for the study of intravitreal inflammation using proteomic analyses.

Small High-Risk Uveal Melanomas Have a Lower Mortality Rate.

Our aim was to determine whether size impacts on the difference in metastatic mortality of genetically high-risk (monosomy 3) uveal melanomas (UM). We undertook a retrospective analysis of data from a patient cohort with genetically characterized UM. All patients treated for UM in the Liverpool Ocular Oncology Centre between 2007 and 2014, who had a prognostic genetic tumor analysis. Patients were subdivided into those with small (≤2.5 mm thickness) and large (>2.5 mm thickness) tumors. Survival analyses were performed using Gray rank statistics to calculate absolute probabilities of dying as a result of metastatic UM. The 5-year absolute risk of metastatic mortality of those with small monosomy 3 UM was significantly lower (23%) compared to the larger tumor group (50%) (p = 0.003). Small disomy 3 UM also had a lower absolute risk of metastatic mortality (0.8%) than large disomy 3 UM (6.4%) (p = 0.007). Hazard rates showed similar differences even with lead time bias correction estimates. We therefore conclude that earlier treatment of all small UM, particularly monosomy 3 UM, reduces the risk of metastatic disease and death. Our results would support molecular studies of even small UM, rather than 'watch-and-wait strategies'.

Detecting Progression of Treated Choroidal Melanomas: Is Ultrasonography Necessary?

Prompt detection and treatment of local treatment failure after radiotherapy for choroidal melanoma optimises any opportunities for conserving vision and the eye, possibly reducing an increased risk of metastatic disease. Long-term surveillance is therefore required but is hampered by the perceived need to perform ultrasonography, which may not be available at a patient's local hospital. The aim of this study was to determine whether local treatment failure can reliably be detected with colour fundus photography alone, and, if so, in which patients. Patients were included in the study if diagnosed with local treatment failure between April 2016 and February 2021 after eye-conserving therapy for choroidal melanoma. Wide-field colour and fundal autofluorescence (FAF) images, optical coherence tomography (OCT), and ultrasonography (US) were analysed by two of the authors (GN and UH). The cohort included 87 patients with local treatment failure. In 75 patients with clear media, tumour progression was detected by colour photography alone in 74 (98.7%) patients. Sensitivity was not increased by the addition of either OCT or AF. One patient with clear media developed extraocular extension detected with US without visible change in the intraocular part of the tumour. In the other 12 patients, US was required because of opaque media and a consequently poor fundal view. Local treatment failure after radiotherapy for choroidal melanoma is detected in 98.7% of cases with colour photography when the media are clear. Ultrasonography is useful when photography is prevented by opaque media or tumours having locations in the far periphery.

Cost-utility analysis of a decade of liver screening for metastases using the Liverpool Uveal Melanoma Prognosticator Online (LUMPO).

This paper outlines a method for cost-utility analysis of liver screening for metastases in patients with posterior uveal melanoma (UM). A semiparametric model of the cumulative incidence of onset of liver metastases was fitted to a retrospective data set of 615 subjects with clinical follow-up with respect to liver surveillance imaging and outcome. The model was internally validated via bootstrap resampling in terms of its discrimination and calibration performance. Receiver operating characteristics (ROC) were derived at different time points. The discrimination performances are consistent across time. The area under the ROC curve at 5 years post treatment was 0.85 [95% CI: 0.81-0.88]. A goodness-of-fit test gives χ2(10)=5.3,p=0.9 demonstrating no evidence against the null hypothesis of zero difference between observed and expected onset of metastatic events. Results showed that at 80% sensitivity, 87% of UM patients will avoid unnecessary radiological scans. This provides potential cost savings of between £46,000 and £97,000 per year to the National Health Service assuming 600 new cases per year.