Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients.

BACKGROUND: Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity. METHODS: We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens. RESULTS: Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3-4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers. CONCLUSIONS: Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma.

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive.

Workload and Injury in Professional Soccer Players: Role of Injury Tissue Type and Injury Severity.

The purpose of the present study was to examine the influence of workload prior to injury on injury (tissue type and severity) in professional soccer players. Twenty-eight days of retrospective training data prior to non-contact injuries (n=264) were collated from 192 professional soccer players. Each injury tissue type (muscle, tendon and ligament) and severity (days missed) were categorised by medical staff. Training data were recorded using global positioning system (GPS) devices for total distance (TD), high speed distance (HSD,>5.5 m/s-1), and sprint distance (SPR,>7.0 m/s-1). Accumulated 1, 2, 3, 4-weekly loads and acute:chronic workload ratios (ACWR) (coupled, uncoupled and exponentially weighted moving average (EWMA) approaches) were calculated. Workload variables and injury tissue type were compared using a one-way ANOVA. The association between workload variables and injury severity were examined using a bivariate correlation. There were no differences in accumulated weekly loads and ACWR calculations between muscle, ligament, and tendon injuries (P>0.05). Correlations between each workload variable and injury severity highlighted no significant associations (P>0.05). The present findings suggest that the ability of accumulated weekly workload or ACWR methods to differentiate between injury type and injury severity are limited using the present variables.

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

Incomplete contingency tables with censored cells with application to estimating the number of people who inject drugs in Scotland.

Estimating the size of hidden or difficult to reach populations is often of interest for economic, sociological or public health reasons. In order to estimate such populations, administrative data lists are often collated to form multi-list cross-counts and displayed in the form of an incomplete contingency table. Log-linear models are typically fitted to such data to obtain an estimate of the total population size by estimating the number of individuals not observed by any of the data-sources. This approach has been taken to estimate the current number of people who inject drugs (PWID) in Scotland, with the Hepatitis C virus diagnosis database used as one of the data-sources to identify PWID. However, the Hepatitis C virus diagnosis data-source does not distinguish between current and former PWID, which, if ignored, will lead to overestimation of the total population size of current PWID. We extend the standard model-fitting approach to allow for a data-source, which contains a mixture of target and non-target individuals (i.e. in this case, current and former PWID). We apply the proposed approach to data for PWID in Scotland in 2003, 2006 and 2009 and compare with the results from standard log-linear models.

Retrospective analysis on the outcomes of contact lens-associated keratitis in a tertiary centre: an evidence-based management protocol to optimise resource allocation.

BACKGROUND/AIMS: Contact lens-associated keratitis (CLAK) is a common sight-threatening complication of contact lens use. Current management protocols in the UK are based on historical practice and necessitate a review for every patient within 48 hours regardless of severity, increasing the treatment burden on a resource-limited healthcare service. Our study aims to identify the different risk factors associated with CLAK, categorise CLAK using a novel grading system and recommend modifications to current management protocols based on the outcomes in the individual subgroups. METHODS: The retrospective cohort study identified 161 eyes from 153 patients with CLAK from the electronic patient records of a tertiary eye centre between 1 July 2021 and 28 February 2022. Patients were categorised based on epithelial defect size (grade 1: <1.0 mm, grade 2: 1.0-2.0 mm, grade 3: >2.0 mm) and their risk factors, clinical features, treatments and outcomes were analysed. RESULTS: The most significant risk factors for CLAK include extended-wear contact lens, poor hygiene and prolonged duration of wear. Grades 1 and 2 CLAKs have excellent outcomes following an empirical treatment regime with topical moxifloxacin with 96% discharged within 48 hours and 94.1% discharged in 2 weeks, respectively. Grade 3 CLAKs require prolonged average duration of treatment. CONCLUSION: We recommend typical grade 1 and 2 CLAKs can be discharged with empirical fluoroquinolone treatment. Grade 3 and all CLAKs with atypical features require monitoring for resolution, further diagnostics or treatment. We provide an evidence-based approach to reduce unnecessary patient visits and optimise resource allocation in an urban setting.

Local tumour control and patient survival after ruthenium-106 brachytherapy for small choroidal melanoma.

AIM: To report local tumour control, metastasis and survival rates of patients with small choroidal melanoma (CM) after treatment with ruthenium-106 (Ru-106) plaque brachytherapy. METHODS: Retrospective case series of 353 consecutive eyes with small CM (thickness ≤2.5 mm and largest basal diameter ≤16 mm) treated with Ru-106 brachytherapy at the London Ocular Oncology Service, between October 2004 and May 2019. RESULTS: The final cohort included 310 eyes and tumour recurrence was observed in 52 (17%) eyes. Ocular retention rate was 96%. Metastatic disease and tumour-related death occurred in 18 (5.8%) and 12 (3.9%) patients, respectively. Metastases were diagnosed after a median of 54 (54±35; range 3.6-118) months from initial treatment. Kaplan-Meier estimates for tumour recurrence, melanoma-related metastases and survival were 17% (95% CI 13.3% to 22.9%), 4.8% (95% CI 2.6% to 8.5%) and 98% (95% CI 94.4% to 99.1%) at 5 years and 26% (95% CI 18.3% to 35.3%), 16% (95% CI 8.7% to 27.7%) and 92% (95% CI 84.5% to 95.7%) at 10 years, respectively. On multivariable analysis, factors predictive for tumour recurrence included juxtapapillary location, larger plaque and final tumour thickness, and for metastasis exudative retinal detachment. CONCLUSION: Small CMs treated with Ru-106 brachytherapy show recurrence and death rates of 17% and 2% at 5 years and 26% and 8% at 10 years. As small CMs have better prognosis than large tumours, early treatment is the key for better survival outcomes.

Injecting drug users in Scotland, 2006: Listing, number, demography, and opiate-related death-rates.

Using Bayesian capture-recapture analysis, we estimated the number of current injecting drug users (IDUs) in Scotland in 2006 from the cross-counts of 5670 IDUs listed on four data-sources: social enquiry reports (901 IDUs listed), hospital records (953), drug treatment agencies (3504), and recent Hepatitis C virus (HCV) diagnoses (827 listed as IDU-risk). Further, we accessed exact numbers of opiate-related drugs-related deaths (DRDs) in 2006 and 2007 to improve estimation of Scotland's DRD rates per 100 current IDUs. Using all four data-sources, and model-averaging of standard hierarchical log-linear models to allow for pairwise interactions between data-sources and/or demographic classifications, Scotland had an estimated 31700 IDUs in 2006 (95% credible interval: 24900-38700); but 25000 IDUs (95% CI: 20700-35000) by excluding recent HCV diagnoses whose IDU-risk can refer to past injecting. Only in the younger age-group (15-34 years) were Scotland's opiate-related DRD rates significantly lower for females than males. Older males' opiate-related DRD rate was 1.9 (1.24-2.40) per 100 current IDUs without or 1.3 (0.94-1.64) with inclusion of recent HCV diagnoses. If, indeed, Scotland had only 25000 current IDUs in 2006, with only 8200 of them aged 35+ years, the opiate-related DRD rate is higher among this older age group than has been appreciated hitherto. There is counter-balancing good news for the public health: the hitherto sharp increase in older current IDUs had stalled by 2006.

Did the UK's COVID-19 restrictions during 2020 have a differential impact on the well-being of the LGBQ+ population: a mixed methods study.

OBJECTIVE: The social distancing measures governments implemented in response to the COVID-19 pandemic have had substantial impacts. For some communities, these impacts will be disproportionate, with those communities experiencing inequalities, marginalisation or discrimination facing specific challenges. Lesbian, gay, bisexual, queer and allied (LGBQ+) communities experience a range of well-being inequalities that may have been impacted by the pandemic. The study aimed to assess the comparative impact of the UK's response to COVID-19 on LGBQ+ communities. DESIGN: A mixed-method explanatory sequential study of the general population using a cross-sectional online survey and semistructured interviews. SETTING: Community, North West of England. PARTICIPANTS: Adults aged 18 years and over; 1540 participated in the survey (192, 12%, LGBQ+) with 49 undergoing semistructured interviews (15 LGBQ+) during spring and summer of 2020. RESULTS: Survey findings indicated that LGBQ+ people experienced similar positive and negative impacts to the rest of the population, but some negative impacts were more marked among the LGBQ+ community. LGBQ+ participants were more likely to disagree that 'the government considered the impact on people like you' when preparing guidance. They were significantly more likely to report being unable to access sufficient food and required medication, eating less healthily, exercising less regularly, experiencing poorer quality sleep and taking more pain medicine than usual. Interview data supported these differences; isolation, being unable to access social networks and concerns about health were commonly discussed by the LGBQ+ participants. Positive impacts, including better work-life balance, were similar across both groups. CONCLUSIONS: The findings indicate LGBQ+ communities' wellbeing inequalities have been compounded by the social distancing restrictions, for example, by impacts on social networks increasing loneliness. Preparedness planning for future pandemics should include equality impact assessments for potential interventions.

Increasing prevalence of chronic hepatitis B virus infection and low linkage to care in Denmark on 31 December 2016 - an update based on nationwide registers.

OBJECTIVES: We aimed to update the estimated prevalence of both diagnosed and undiagnosed chronic hepatitis B virus infection in Denmark. Moreover, we aimed to determine the number of people with chronic hepatitis B virus infection in specialised care and to assess the completeness of reporting to the national register of communicable diseases. METHODS: Using four registers with national coverage, we identified all individuals registered with chronic hepatitis B virus infection, aged 16 years or older, and alive in Denmark on 31 December 2016. The diagnosed population was then estimated using capture-recapture analysis. The undiagnosed population was estimated using data from the Danish pregnancy screening program. RESULTS: We estimated that 14,548 individuals were living with chronic hepatitis B virus infection corresponding to 0.3% of the Danish population. Of them, 13,530 (93%) were diagnosed and 7942 (55%) were registered in one or more of the source registers. Only 4297 (32%) diagnosed individuals had attended specialised care and only 3289 cases (24%) were reported to the Danish communicable disease register. CONCLUSION: The prevalence of chronic hepatitis B virus infection increased from 2007 to 2017. The majority that had been diagnosed did not receive care as recommended by national guidelines and were not reported to the communicable diseases register responsible for hepatitis B virus surveillance. Future efforts should focus on linking individuals diagnosed with chronic hepatitis B virus infection to specialised care and improving reporting to the hepatitis B virus surveillance system.

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.

A machine learning system to optimise triage in an adult ophthalmic emergency department: a model development and validation study.

Background: A substantial proportion of attendances to ophthalmic emergency departments are for non-urgent presentations. We developed and evaluated a machine learning system (DemDx Ophthalmology Triage System: DOTS) to optimise triage, with the aim of reducing inappropriate emergency attendances and streamlining case referral when necessary. Methods: DOTS was built using retrospective tabular data from 11,315 attendances between July 1st, 2021, to June 15th, 2022 at Moorfields Eye Hospital Emergency Department (MEH) in London, UK. Demographic and clinical features were used as inputs and a triage recommendation was given ("see immediately", "see within a week", or "see electively"). DOTS was validated temporally and compared with triage nurses' performance (1269 attendances at MEH) and validated externally (761 attendances at the Federal University of Minas Gerais - UFMG, Brazil). It was also tested for biases and robustness to variations in disease incidences. All attendances from patients aged at least 18 years with at least one confirmed diagnosis were included in the study. Findings: For identifying ophthalmic emergency attendances, on temporal validation, DOTS had a sensitivity of 94.5% [95% CI 92.3-96.1] and a specificity of 42.4% [38.8-46.1]. For comparison within the same dataset, triage nurses had a sensitivity of 96.4% [94.5-97.7] and a specificity of 25.1% [22.0-28.5]. On external validation at UFMG, DOTS had a sensitivity of 95.2% [92.5-97.0] and a specificity of 32.2% [27.4-37.0]. In simulated scenarios with varying disease incidences, the sensitivity was ≥92.2% and the specificity was ≥36.8%. No differences in sensitivity were found in subgroups of index of multiple deprivation, but the specificity was higher for Q2 when compared to Q4 (Q4 is less deprived than Q2). Interpretation: At MEH, DOTS had similar sensitivity to triage nurses in determining attendance priority; however, with a specificity of 17.3% higher, DOTS resulted in lower rates of patients triaged to be seen immediately at emergency. DOTS showed consistent performance in temporal and external validation, in social-demographic subgroups and was robust to varying relative disease incidences. Further trials are necessary to validate these findings. This system will be prospectively evaluated, considering human-computer interaction, in a clinical trial. Funding: The Artificial Intelligence in Health and Care Award (AI_AWARD01671) of the NHS AI Lab under National Institute for Health and Care Research (NIHR) and the Accelerated Access Collaborative (AAC).

Hepatitis C prevalence in Denmark -an estimate based on multiple national registers.

BACKGROUND: A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. METHODS: Patients with a diagnosis of chronic hepatitis C were identified from four national registers: a laboratory register, the Hospital Discharge Register, a clinical database of chronic viral hepatitis and the Register of Communicable Diseases. The total population diagnosed with hepatitis C was estimated by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. RESULTS: A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population diagnosed with the disease was 9,166 persons (95% C.I. interval 8,973 - 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the Danish population over 15 years of age. The prevalence was highest among persons 40-49 years old (0.39%) and males (0.28%). It was estimated that 40% of the diagnosed patients lived in the capital region, and 33.5% had attended specialised healthcare. It was estimated that 46% of hepatitis C patients had not been diagnosed and the total population with chronic hepatitis C in Denmark was 16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the population over 15 years of age. CONCLUSIONS: The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care.

Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma.

PURPOSE: To report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL). METHODS: Retrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year). RESULTS: From April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5-34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5-104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma). CONCLUSIONS: Intravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this.

A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.

Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI-PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose-expansion study of patients with argininosuccinate synthetase (ASS1)-deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m2 ) and Cis (75 mg/m2 ) every 3 weeks plus weekly intramuscular ADI (36 mg/m2 ), followed by maintenance ADI until progression (NCT02029690). Ten of fourteen ASS1-deficient patients with UM liver metastases and a median of one line of prior immunotherapy received ADIPemCis. Only one ≥ grade 3 adverse event of febrile neutropenia was reported. Seven patients had stable disease with a median progression-free survival of 3.0 months (range, 1.3-8.1) and a median overall survival of 11.5 months (range, 3.2-36.9). Despite anti-ADI-PEG20 antibody emergence, plasma arginine concentrations remained suppressed by 18 weeks with a reciprocal increase in plasma citrulline. Tumour rebiopsies at progression revealed ASS1 re-expression as an escape mechanism. ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional anti-metabolite strategies.

Prospective validation of a virtual clinic pathway in the management of choroidal naevi: the NAEVUS study Report no. 1: safety assessment.

BACKGROUND: Choroidal naevi are a common incidental finding prompting specialist referrals to ocular oncology. Rarely, such lesions have sufficient suspicious features to diagnose a small melanoma. The aim of the study is to show that 'virtual' imaging-based pathways are a safe and efficient option to manage such referrals. METHODS: A prospective cohort study at the Manchester Royal Eye Hospital and Moorfields Eye Hospital between June 2016 and July 2017 of the management decision of 400 patients reviewed by an ophthalmologist in a face-to-face consultation (gold standard) supported by fundus photography, optical coherence tomography, autofluorescence (AF) and B-mode ultrasound. The images were also read independently by blinded graders (non-medical) and blinded ophthalmologists, and a management decision was made based on image review alone (virtual pathway). The two pathways were compared for safety. RESULTS: The agreement for management decisions between face-to-face and virtual pathways was 83.1% (non-medical) and 82.6% (medical). There were more over-referrals in the virtual pathway (non-medical 24.3%, medical 23.3% of gold standard discharge) and only two under-referrals (10.5% of gold standard referrals), both borderline cases with minimal clinical risk. The agreement for risk factors of growth (orange pigment, subretinal fluid, hyper-AF) ranged between 82.3% and 97.3%. CONCLUSIONS: We prospectively validated a virtual clinic model for the safe management of choroidal naevi. Such a model of care is feasible with low rate of under-referral. An over-referral rate of almost 24% from the vitrual pathway needs to be factored into designing such pathways in conjunction with evidence on their cost-effectiveness.

Treating Choroidal Metastases and Improving Vision with Osimertinib in EGFR T790M-Mutated Lung Adenocarcinoma: A Case Report and Review of the Literature.

A 41-year-old never-smoking female was diagnosed with epidermal growth factor receptor (EGFR)-mutated T2bN3M1b lung adenocarcinoma with axillary lymph nodes. She complained of blurred vision in the left eye (2/60) and was subsequently found to have a left choroidal metastasis. Treatment with tyrosine kinase inhibitor (TKI) erlotinib was started, and after 1 year of disease stability, she developed unsteadiness and worsening visual disturbance (1/60). Brain imaging showed 24 new brain metastases, which were treated with Gamma Knife stereotactic radiosurgery. An enlarging axillary lymph node was biopsied, which identified the T790M mutation, and she commenced the novel TKI osimertinib. Three weeks later, her choroidal lesion had regressed from 3.1 mm to 2.2 mm, and after 2 months of osimertinib, her visual acuity had improved to 6/9. At the last follow-up 8 months after initiation of osimertinib, her choroidal metastasis remains stable, and visual acuity has improved to 6/6. Evidence suggests that osimertinib's efficacy in treating cerebral metastases is superior to that of chemotherapy and other EGFR-TKIs (gefitinib and erlotinib); however, the literature is sparse with regards to the use of osimertinib for the treatment of intraocular disease. In this case, the need for intense daily radiation treatment with its associated toxicities was negated, and as such we propose that osimertinib may be a promising treatment for choroidal metastasis secondary to EGFR-mutated lung adenocarcinoma.

Reply to Comment on Roelofs, K.A.; et al. "Detecting Progression of Melanocytic Choroidal Tumours by Sequential Imaging: Is Ultrasonography Necessary?" Cancers 2020, 12, 1856.

We thank Capasso et al [...].