Vitrectomy as an Adjunct to Treat-and-Extend Anti-VEGF Injections for Diabetic Macular Edema: The Vitrectomy in Diabetic Macular Oedema (VIDEO) Randomized Clinical Trial.

Importance: There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy. Objective: To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME). Design, Setting, and Participants: This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 µm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023. Interventions: Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization. Main Outcomes and Measures: Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate. Results: Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] µm for the control group vs -32 [-48 to 25] µm for the vitrectomy group; difference, 62 µm; 95% CI, -110 to 11; P = .11). Conclusions and Relevance: Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME. Trial Registration: isrctn.org Identifier: ISRCTN59902040.

Deferral of Treatment for Small Choroidal Melanoma and the Risk of Metastasis: An Investigation Using the Liverpool Uveal Melanoma Prognosticator Online (LUMPO).

BACKGROUND: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. METHODS: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. RESULTS: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. CONCLUSIONS: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year.

Associations between empirically proportionate and disproportionate fears of cancer recurrence and anxiety and depression in uveal melanoma survivors: Five-year prospective study.

OBJECTIVE: Fear of cancer recurrence (FCR) may develop into elevated anxiety or depression symptoms, but few risk factors for this development are known. Objective recurrence risk estimation is possible in some cancers. Using theories of risk communication and phobias, we examined whether the proportionality of FCR to known objective recurrence risk influences the development of anxiety and depression symptoms. METHOD: Uveal melanoma (UM) patients can opt for reliable prognostic testing. Patients experience either a 'good' or 'poor' prognostic outcome, whereby 10-year mortality due to metastatic disease is, respectively, low or high. In a five-year prospective study of a consecutive sample of 589 UM survivors, we used random intercept cross lagged panel analyses to examine whether proportionality differentially influences whether FCR progresses to anxiety and depression. RESULTS: Positive cross paths predicting anxiety from FCR were stronger in the poor prognosis group than the good prognosis and not tested groups. Prognostic group differences were not evident for depression. CONCLUSIONS: FCR was more likely to progress to elevated anxiety symptoms when proportionate to the known objective recurrence risk. Objective evidence may play a prominent role in the development and structure of fear because it assumes a high epistemic weight that activates a wide range of emotional and cognitive responses. Interventions that assist survivors to tolerate FCR in the presence of higher recurrence risks may be important in reducing anxiety symptoms.

Prevalence, temporal course and risk factors for phantom eye symptoms in uveal melanoma.

BACKGROUND: Phantom eye symptoms (PES), particularly phantom visual sensations (PVS) and phantom eye pain (PEP), are common in enucleated patients and can lead to psychological distress. Current cross-sectional studies cannot examine the temporal course of symptoms, nor can they identify dynamic risk factors or consequences of PES. METHODS: Cohort study of 105 enucleated uveal melanoma patients returning self-report questionnaires, within 4 weeks of diagnosis and 6-, 12- and 24-months post-treatment. Questionnaires measuring PVS and PEP symptoms in the week prior to completion, pain severity, Hospital Anxiety and Depression Scale scores and the Functional Assessment of Cancer Therapy scale (FACT-G) measuring quality of life. RESULTS: PVS and PEP emerged after 6 months, were relatively stable over the study and did not remit. PVS showed 6-, 12- and 24-month prevalence rates of 44.6%, 48.2% and 30.2%, and PEP 16.1%, 18.4% and 17.5% respectively. PVS were generally elementary, with only 10-15% of the total cohort experiencing complex sensations. PEP was generally neither prolonged nor intense, except in a small proportion. PVS and PEP were showed moderate associations but did not predict each other prospectively. Anxiety within 4 weeks of diagnosis was a risk factor for the initiation of PEP. Neither PVS nor PEP prospectively predicted anxiety, depression or quality of life. CONCLUSIONS: PES were prevalent and non-remitting, beginning within 6 months of enucleation. PVS and PEP may not represent symptoms of a coherent syndrome. We discuss findings with reference to theories of phantom sensations, and directions for clinical practise and research.

Tumor-Associated Retinal Pigmentation in Choroidal Melanoma.

PURPOSE: To report a previously unrecognized choroidal melanoma clinical feature termed tumor-associated retinal pigmentation (TARP) and determine any correlation with tumor biology. DESIGN: Imaging and histologic analysis of a retrospective cohort of patients. PARTICIPANTS: Patients with choroidal melanoma identified as having TARP on funduscopy at the Liverpool Ocular Oncology Centre (LOOC), United Kingdom, from January 2020 through January 2023. METHODS: Clinical and imaging characteristics of patients diagnosed with choroidal melanoma and exhibiting TARP on fundoscopy were documented. Details of these choroidal melanomas were collated and correlated with histopathology and molecular genetic reports. The chromosome 3 status of each tumor was assessed. In enucleated samples, immunostaining was undertaken to determine the nature of the TARP using specific markers (CD68 and MelanA). MAIN OUTCOME MEASURES: Features of TARP on widefield fundus color imaging, fundus autofluorescence (FAF), and OCT were described. Tumor chromosome 3 status and the immunoprofile of the TARP also were collated. RESULTS: Tumor-associated retinal pigmentation had a prevalence rate of 7.47 per 100 cases of choroidal melanoma at the LOOC. Twenty-three eyes with TARP were analyzed, with a mean age of 71.4 years (range, 51-88 years). The median largest basal diameter was 16.10 mm (range, 9.17-21.32 mm), and the mean tumor thickness was 8.04 mm (range, 1.40-13.80 mm). Tumor-associated retinal pigmentation was observed on widefield color fundus imaging, with hypofluorescence on FAF images and represented hyperreflective foci located in intraretinal and subretinal spaces on OCT scans. Seventeen patients (73.9%) underwent enucleation, and 6 patients (26.1%) underwent globe-sparing treatment. Molecular genetic analysis of 20 choroidal melanomas (after enucleation or radiotherapy biopsy) revealed monosomy 3 in 18 tumors (90%). Immunostaining of the TARP in enucleated eyes showed CD68+ melanophages in all 17 patients appearing as scattered cells and aggregates; MelanA findings were negative. CONCLUSIONS: Tumor-associated retinal pigmentation represents tumor-associated macrophages, not melanocytes, within intraretinal and subretinal spaces of larger choroidal melanomas. Radiation treatments need not involve this area in the treatment plan, minimizing radiation-related complications. This novel clinical sign seems to be linked to tumors of high metastatic-risk clinical and genetic characteristics, with a preponderance having monosomy 3 anomalies. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Sensitivity and Specificity of Different Prognostic Systems in Guiding Surveillance for Metastases in Uveal Melanoma.

Uveal melanoma (UM) metastasises in ~50% of patients, most frequently to the liver. Surveillance imaging can provide early detection of hepatic metastases; however, guidance regarding UM patient risk stratification for surveillance is unclear. This study compared sensitivity and specificity of four current prognostic systems, when used for risk stratification for surveillance, on patients treated at the Liverpool Ocular Oncology Centre (LOOC) between 2007-2016 (n = 1047). It found that the Liverpool Uveal Melanoma Prognosticator Online III (LUMPOIII) or Liverpool Parsimonious Model (LPM) offered greater specificity at equal levels of sensitivity than the American Joint Committee on Cancer (AJCC) system or monosomy 3 alone, and suggests guidance to achieve 95% sensitivity and 51% specificity (i.e., how to detect the same number of patients with metastases, while reducing the number of negative scans). For example, 180 scans could be safely avoided over 5 years in 200 patients using the most specific approach. LUMPOIII also offered high sensitivity and improved specificity over the AJCC in the absence of genetic information, making the result relevant to centres that do not perform genetic testing, or where such testing is inappropriate or fails. This study provides valuable information for clinical guidelines for risk stratification for surveillance in UM.

Side Effects of Proton Beam Radiotherapy Treatment on Iris Melanoma.

PURPOSE: This study evaluated the functional outcome and ocular side effects of patients receiving proton beam radiotherapy (PBR) for the treatment of iris melanoma (IM). DESIGN: This retrospective study analyzed prospectively collected data. PARTICIPANTS: Patients with IM who underwent PBR as a primary treatment. METHODS: Treatment was given in the form of whole PBR (wPBR: n = 51) or segmental PBR (sPBR: n = 98). MAIN OUTCOME MEASURES: Visual acuity (VA) and side effects were divided into ocular surface disease (OSD), secondary glaucoma, or cataract development. RESULTS: A total of 149 eyes of 149 patients with a mean age of 53.9 ± 16.0 years were included. Tumor recurrence developed in 3 patients (wPBR: 1/51; sPBR: 2/98). Ocular surface disease was observed in 78.4% of the wPBR group (40/51) and 25.5% of the sPBR group (25/98) (P < 0.001) after 0.7 ± 1.2 years and 1.1 ± 0.9 years, respectively. The main side effect was dry eye syndrome in both groups, but severe side effects such as limbal stem cell failure were found only in the wPBR group (4/51; 7.8%). Secondary glaucoma developed in 31.4% of the wPBR group (16/51) compared with 1.0% in the sPBR group (1/98; P < 0.001). Glaucoma control was generally achieved with eye drops, whereas surgery was necessary in 5 patients (wPBR: 4/51, 7.8%; sPBR: 1/98, 1%). Cataract surgery was performed in 47.9% of the wPBR group (23/48) and 19.8% of the sPBR group (19/96) (P < 0.001). Before treatment, VA was 0.14 ± 0.27 logarithm of the minimum angle of resolution (logMAR) in the wPBR group and 0.04 ± 0.19 logMAR in the sPBR group. A worsening was seen in the wPBR group (0.55 ± 0.16 logMAR; P < 0.001) 6 months after radiotherapy, which normalized after 12 months (0.15 ± 0.30 logMAR; P = 0.17). In the sPBR group, no such decrease in VA was observed (6 months: 0.03 ± 0.22 logMAR, P = 0.54; 12 months: 0.04 ± 0.21 logMAR, P = 0.98). CONCLUSIONS: Our results demonstrate that PBR is a very successful treatment option for patients with IM, showing a high tumor control rate and relatively low complication profile. Tumor recurrence was a rare event, and secondary enucleation was not necessary in any patient. Side effects are commonly seen, but severe side effects such as limbal stem cell failure or secondary glaucoma mainly developed after wPBR. These results are important for clinical decision making and discussion with the patient regarding this form of radiotherapy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Conjunctival Pigmentation Following Pars Plana Vitrectomy (PPV) for Rhegmatogenous Retinal Detachment: Risk Factors and Outcomes.

PURPOSE:  To investigate the incidence and the risk factors for conjunctival pigmentation at the sclerotomy sites following valved and non-valved cannula pars plana vitrectomy (PPV) performed by different surgical techniques. METHODS:  This is a prospective observational study which included 70 eyes of 70 patients who underwent PPV for rhegmatogenous retinal detachment with follow-up visits at 1, 3, 6, 12, and 24 months. Twenty-eight eyes were operated using 25G non-valved cannulas (Group A), 22 eyes using 25G non-valved cannulas (Group B), and 20 eyes using 25G valved cannulas (Group C). The evaluated clinical parameters include the surgical technique, the patients' age, the number of retinal tears, the tamponade agent, the presence of residual sub-retinal fluid (SRF), and the duration of postoperative posturing. RESULTS:  Group A was associated with significant conjunctival pigmentation at up to 6 months after PPV. Sulfur hexafluoride (SF6) gas tamponade was associated with less conjunctival pigmentation at 3 months follow-up visit [odds ratio, OR 0.09 (95% confidence interval, CI 0.01; 0.67)], whereas the presence of residual SRF was a significant risk factor for postoperative pigmentation at 1-year follow-up visit [OR 5.89 (95% CI 1.84; 23.12)]. The area of measured pigmentation was also positively correlated to the number of retinal tears at all follow-up visits over 2 years. Six patients presented with conjunctival pigmentation at 2 years follow-up visit. CONCLUSION:  New vitrectomy techniques with valved cannulas prevent the postoperative appearance of conjunctival pigmentation. The number of retinal tears, the presence of SRF, and the use of long-standing tamponade agents were the most significant predisposing factors. The post-vitrectomy conjunctival pigmentation gradually reduces over time.

Diagnostic imaging of retinal astrocytomas: A case-series.

OBJECTIVES: To use multimodal imaging techniques to characterise features of retinal astrocytomas (RA) which would aid practitioners distinguish them from other causes of non-pigmented fundal lesions. METHODS: Retrospective analysis of notes and imaging of 17 patients diagnosed with RA at a single centre between January 2012 and June 2021 was conducted. Demographics, examination findings and imaging including colour fundus photography, optical coherence tomography (OCT), infra-red (IR) and ultrasound (US) were analysed. These were compared to differential diagnoses, including retinoblastomas, amelanotic choroidal melanomas, choroidal metastases and idiopathic scleromas. RESULTS: Fourteen patients (82%; 14/17) had idiopathic RA and three (18%; 3/17) were associated with tuberous sclerosis. Mean age at presentation was 43 years. Twelve patients (71%; 12/17) were asymptomatic. Thirteen (76%; 13/17) had better than 6/12 vision, with 41% (7/17) better than 6/6. All lesions were creamy-white. There were two distinct appearances, seven (39%; 7/18) were poorly-defined translucent retinal elevations and eleven (61%; 11/18) were well-defined solid opaque retinal masses. Six (33%; 6/18) displayed clustered, calcified spherules giving them the pathognomonic 'mulberry-like' appearance. On OCT, all appeared as dome-shaped retinal thickening with disruption of the inner retinal layers and nine (60%; 9/15) had intra-retinal cystic spaces giving a 'moth-eaten' appearance. Mean basal diameter and thickness on OCT was 2.93 mm and 0.86 mm, respectively. High internal reflectivity on US was noted in 92% (11/12). CONCLUSIONS: RAs display characteristic clinical, demographic and imaging features which can aid differentiating them from other non-pigmented fundal lesions. We advise using multiple imaging modalities when diagnosing these lesions.

Fear of cancer recurrence and adverse cancer treatment outcomes: predicting 2- to 5-year fear of recurrence from post-treatment symptoms and functional problems in uveal melanoma survivors.

OBJECTIVE: The fear of cancer recurrence (FCR) in later survivorship can lead to poorer mental health, quality of life and physical and functional recovery. Later-occurring FCR may be a consequence of late-emerging physical symptoms and functional problems from cancer or its treatment. Based on the self-regulation model, we predicted that persistent or escalating symptoms and functional problems would prospectively predict FCR observed 2-5 years after diagnosis and treatment. METHODS: This is a five-year study of 708 uveal melanoma (UM) patients, measuring self-reported visual and ocular symptoms, functional problems and FCR at 6, 12, 24, 36, 48 and 60 months post-diagnosis. A mixed measures design over four levels with observations staggered to represent prospective prediction. Criterion variables were FCR at 24, 36, 48 and 60 months. Predictors were symptom and function scores measured at the previous two observations to FCR. Controls were FCR measured at the previous observation to the criterion FCR measure and demographic, clinical and treatment variables. RESULTS: Linear mixed modelling showed that FCR was uniquely predicted by enduring symptoms, those that emerged two observations previously, but not symptoms arising at the previous observation. FCR was predicted by functional problems, which emerged in the observation prior to FCR, but not the observation previous to that. CONCLUSIONS: Persistent or emerging post-treatment symptoms and functional limitations are probable risk factors for late-occurring FCR in UM survivors. IMPLICATIONS FOR CANCER SURVIVORS: Monitoring symptoms and functional limitations assists in identifying at-risk survivors and targeting preventive interventions. Self-regulation theory suggests that helping survivors to more realistically appraise symptoms and functional problems may prevent FCR.

A Retrospective Analysis of 10 Years of Liver Surveillance Undertaken in Uveal Melanoma Patients Treated at the Supraregional "Liverpool Ocular Oncology Centre", UK.

PURPOSE: To determine liver screening frequency and modality in UM patients following primary treatment, and the characteristics of detected metastases. METHODS: A 10-year retrospective study of 615 UM patients undergoing liver surveillance in Liverpool. Information was collected from liver scan reports of these patients. RESULTS: Of 615 UM patients analyzed, there were 337 men (55%) and 278 women (45%). Median age at primary treatment was 61 years (range, 22-94). At study end, median follow-up was 5.1 years, with 375 patients (61%) alive and 240 deceased (39%). Of the deceased patients, 187 (78%) died due to metastatic UM; 24 (10%) deaths were due to other causes; and 29 (12%) patients died of unknown conditions. In total, 3854 liver scans were performed in the 615 UM patients, with a median of 6.2 scans per patient (range, 1-40). Liver MRI was most frequently performed (62.8%). In total, 229 (37%) UM patients developed metastases during the study period: 150 were detected via liver surveillance and 79 were observed post-mortem. CONCLUSIONS: Metastatic UM onset is related to the size and genetic profiles of the primary UM, and can be predicted using the model LUMPO3. Regular liver surveillance allowed for timely detection of metastases, and through metastasectomy can lead to prolongation of life in some patients.

'I Don't Like Uncertainty, I Like to Know': How and why uveal melanoma patients consent to life expectancy prognostication.

BACKGROUND: Technological advances have led to cancer prognostication that is increasingly accurate but often unalterable. However, a reliable prognosis of limited life expectancy can cause psychological distress. People should carefully consider offers of prognostication, but little is known about how and why they decide on prognostication. Using uveal melanoma (UM) patients, we aimed to identify (i) how and why do people with UM decide to accept prognostication and (ii) alignment and divergence of their decision-making from conceptualizations of a 'well-considered' decision. METHODS: UM provides a paradigm to elucidate clinical and ethical perspectives on prognostication, because prognostication is reliable but prognoses are largely nonameliorable. We used qualitative methods to examine how and why 20 UM people with UM chose prognostication. We compared findings to a template of 'well-considered' decision-making, where 'well-considered' decisions involve consideration of all likely outcomes. RESULTS: Participants wanted prognostication to reduce future worry about uncertain life expectancy. They spontaneously spoke of hoping for a good prognosis when making their decisions, but largely did not consider the 50% possibility of a poor prognosis. When pressed, they argued that a poor outcome at least brings certainty. CONCLUSIONS: While respecting decisions as valid expressions of participants' wishes, we are concerned that they did not explicitly consider the realistic possibility of a poor outcome and how this would affect them. Thus, it is difficult to see their decisions as 'well-considered'. We propose that nondirective preference exploration techniques could help people to consider the possibility of a poor outcome. PATIENT OR PUBLIC CONTRIBUTION: This paper is a direct response to a patient-identified and defined problem that arose in therapeutic and conversational discourse. The research was informed by the responses of patient participants, as we used the material from interviews to dynamically shape the interview guide. Thus, participants' ideas drove the analysis and shaped the interviews to come.

Is accurate routine cancer prognostication psychologically harmful? 5-year outcomes of life expectancy prognostication in uveal melanoma survivors.

PURPOSE: Prognostication in cancer is growing in importance as increasingly accurate tools are developed. Prognostic accuracy intensifies ethical concerns that a poor prognosis could be psychologically harmful to survivors. Uveal melanoma (UM) prognostication allows survivors to be reliably told that life expectancy is either normal (good prognosis) or severely curtailed because of metastatic disease (poor prognosis). Treatment cannot change life expectancy. To identify whether prognosis is associated with psychological harm, we compared harm in UM survivors with good and poor prognoses and those who declined testing and compared these outcomes to general population norms. METHODS: Non-randomized 5-year study of a consecutive series of 708 UM survivors (51.6% male, mean age 69.03, SD=12.12) with observations at 6, 12, 24, 36, 48 and 60 months. We operationalized psychological harm as anxiety and depression symptoms, worry about cancer recurrence (WREC) and poor quality of life (QoL). RESULTS: Compared to other groups, survivors with poor prognoses showed initially elevated anxiety and depression and consistently elevated worry about local or distant recurrence over 5 years. Good prognoses were not associated with outcomes. Generally, no prognostic groups reported anxiety, depression and WREC or QoL scores that exceeded general population norms. CONCLUSIONS: Using a large sample, we found that harm accruing from a poor prognosis was statistically significant over 5 years, but did not exceed general non-cancer population norms. IMPLICATIONS FOR CANCER SURVIVORS: Survivors desire prognostic information. At a population level, we do not believe that our findings show sufficiently strong links between prognostication outcome and psychological harm to deny patients the option of knowing their prognosis. Nonetheless, it is important that patients are informed of potential adverse psychological consequences of a poor prognosis.

Prediction of all-cause mortality from 24 month trajectories in patient-reported psychological, clinical and quality of life outcomes in uveal melanoma patients.

A number of patient-reported outcomes (PROs) predict increased mortality after primary cancer treatment. Studies, though, are sometimes affected by methodological limitations. They often use control variables that poorly predict life expectancy, examine only one or two PROs thus not controlling potential confounding by unmeasured PROs, and observe PROs at only a single point in time. To predict all-cause mortality, this study used control variables affording good estimates of life expectancy, conducted multivariate analyses of multiple PROs to identify independent predictors, and monitored PROs two years after diagnosis. We recruited a consecutive sample of 824 patients with uveal melanoma between April 2008 and December 2014. PROs were variables shown to predict mortality in previous studies; anxiety, depression, visual and ocular symptoms, visual function impairment, worry about cancer recurrence, and physical, emotional, social and functional quality of life (QoL), measured 6, 12 and 24 months after diagnosis. We conducted Cox regression analyses with a census date of December 2018. Covariates were age, gender, marital and employment status, self-reported co-morbidities, tumor diameter and thickness, treatment modality and chromosome 3 mutation status, the latter a genetic mutation strongly associated with mortality. Single predictor analyses (with covariates), showed 6-month depression and poorer functional QoL predicting mortality, as did 6-12 month increases in anxiety and 6-12 month decreases in physical and functional QoL. Multivariate analyses using all PROs showed independent prediction by 6-month depression and decreasing QoL over 6-12 months and 12-24 months. Elevated depression scores six months post-diagnosis constituted an increased mortality risk. Early intervention for depressive symptoms may reduce mortality.

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'.

Impact of COVID-19 pandemic on eye cancer care in United Kingdom.

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.

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.