The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

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.

Correlation between BAP1 Localization, Driver Mutations, and Patient Survival in Uveal Melanoma.

Uveal melanoma (UM) is an uncommon but highly aggressive ocular malignancy. Poor overall survival is associated with deleterious BAP1 alterations, which frequently occur with monosomy 3 (LOH3) and a characteristic gene expression profile. Tumor DNA from a cohort of 100 UM patients from Moorfields Biobank (UK) that had undergone enucleation were sequenced for known UM driver genes (BAP1, SF3B1, EIF1AX, GNAQ, and GNA11). Immunohistochemical staining of BAP1 and interphase FISH for chromosomes 3 and 8 was performed, and cellular localization of BAP1 was correlated with BAP1 mutations. Wildtype (WT) BAP1 staining was characterized by nBAP1 expression with <10% cytoplasmic BAP1 (cBAP1). Tumors exhibited heterogeneity with respect to BAP1 staining with different percentages of nBAP1 loss: ≥25% loss of nuclear BAP1 (nBAP1) was superior to chr8q and LOH3 as a prognostic indicator. Of the successfully sequenced UMs, 38% harbored oncogenic mutations in GNA11 and 48% harbored mutations in GNAQ at residues 209 or 183. Of the secondary drivers, 39% of mutations were in BAP1, 11% were in EIF1AX, and 20% were in the SF3B1 R625 hotspot. Most tumors with SF3B1 or EIF1AX mutations retained nuclear BAP1 (nBAP1). The majority of tumor samples with likely pathogenic BAP1 mutations, regardless of mutation class, displayed ≥25% loss of nBAP1. This included all tumors with truncating mutations and 80% of tumors with missense mutations. In addition, 60% of tumors with truncating mutations and 82% of tumors with missense mutations expressed >10% cBAP1.

Genomic surveillance of Salmonella spp. in the Philippines during 2013-2014.

BACKGROUND: Increasing antimicrobial resistance (AMR) in Salmonella has been observed in the Philippines. We aimed to characterise the population and AMR mechanisms of Salmonella with whole genome sequencing (WGS) and compare it with laboratory surveillance methods. METHODS: The serotype, multilocus sequence type, AMR genes and relatedness between isolates were determined from the genomes of 148 Salmonella Typhi (S. Typhi) and 65 non-typhoidal Salmonella (NTS) collected by the Antimicrobial Resistance Surveillance Program during 2013-2014. Genotypic serotypes and AMR prediction were compared with phenotypic data. RESULTS: AMR rates in S. Typhi were low, with sparse acquisition of mutations associated with reduced susceptibility to fluoroquinolones or extended-spectrum beta-lactamases (ESBL) genes. By contrast, 75% of NTS isolates were insusceptible to at least one antimicrobial, with more than half carrying mutations and/or genes linked to fluoroquinolone resistance. ESBL genes were detected in five genomes, which also carried other AMR determinants. The population of S. Typhi was dominated by likely endemic genotype 3.0, which caused a putative local outbreak. The main NTS clades were global epidemic S. Enteritidis ST11 and S. Typhimurium monophasic variant (I,4,[5],12: i: -) ST34. CONCLUSION: We provide the first genomic characterisation of Salmonella from the Philippines and evidence of WGS utility for ongoing surveillance.

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.

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.

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.

Distinguishing Choroidal Nevi from Melanomas Using the MOLES Algorithm: Evaluation in an Ocular Nevus Clinic.

OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of the MOLES scoring system in differentiating choroidal melanomas from nevi according to Mushroom shape, Orange pigment, Large tumor size, Enlarging tumor, and Subretinal fluid (SRF). METHODS: Color photographs, fundus-autofluorescence images, and optical coherence tomography of 222 melanocytic choroidal tumors were reviewed. Each MOLES feature was retrospectively scored between 0 and 2 and tumors categorized as "common nevus," "low-risk nevus," "high-risk nevus," and "probable melanoma" according to the total score. MOLES scores were compared with the experts' diagnosis of melanoma. RESULTS: The MOLES scoring system indicated melanoma in all 81 tumors diagnosed as such by ocular oncologists (100% sensitivity) and nevus in 135 of 141 tumors given this diagnosis by these experts (95.7% specificity). Of the 6 tumors with discordant diagnoses, 4 had basal diameters exceeding 6 mm, all with SRF and/or orange pigment, and 2 small tumors showed either significant SRF with traces of orange pigment, or vice versa. CONCLUSIONS: The MOLES system for diagnosing melanocytic choroidal tumors compares well with expert diagnosis but needs to be evaluated when deployed by ophthalmologists and community optometrists in a wide variety of working environments.

Genomic surveillance of Pseudomonas aeruginosa in the Philippines, 2013-2014.

Pseudomonas aeruginosa is an opportunistic pathogen that often causes nosocomial infections resistant to treatment. Rates of antimicrobial resistance (AMR) are increasing, as are rates of multidrug-resistant (MDR) and possible extensively drug-resistant (XDR) infections. Our objective was to characterize the molecular epidemiology and AMR mechanisms of this pathogen. We sequenced the whole genome for each of 176 P. aeruginosa isolates collected in the Philippines in 2013-2014; derived the multilocus sequence type (MLST), presence of AMR determinants and relatedness between isolates; and determined concordance between phenotypic and genotypic resistance. Carbapenem resistance was associated with loss of function of the OprD porin and acquisition of the metallo-ß-lactamase (MBL) gene bla VIM. Concordance between phenotypic and genotypic resistance was 93.27% overall for six antibiotics in three classes, but varied among aminoglycosides. The population of P. aeruginosa was diverse, with clonal expansions of XDR genomes belonging to MLSTs ST235, ST244, ST309 and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, and of transfer between hospitals. Most of the ST235 genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the Philippines. In addition, long-read sequencing of one representative XDR ST235 isolate identified an integron carrying multiple resistance genes (including bla VIM-2), with differences in gene composition and synteny from the P. aeruginosa class 1 integrons described previously. The survey bridges the gap in genomic data from the Western Pacific Region and will be useful for ongoing surveillance; it also highlights the importance of curtailing the spread of ST235 within the Philippines.

Genomic surveillance of methicillin-resistant Staphylococcus aureus in the Philippines, 2013-2014.

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus clones circulating in the Philippines. We sequenced the whole genomes of 116 S. aureus isolates collected in 2013-2014 within the Antimicrobial Resistance Surveillance Program. The multilocus sequence type, spa type, SCCmec type, presence of antimicrobial resistance (AMR) determinants and virulence genes and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. The MRSA population in the Philippines comprised a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South-West Pacific clone but formed a distinct, diverse lineage, with evidence of global dissemination. We showed independent acquisition of resistance to sulfamethoxazole/trimethoprim in various locations and genetic clones but mostly in paediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for eight antibiotics in seven classes. We have made the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific Region and will constitute the genetic background for contextualizing prospective surveillance.

Genomic surveillance of Neisseria gonorrhoeae in the Philippines, 2013-2014.

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines. We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013-2014 by ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence of the blaTEM gene, the S91F mutation in the gyrA gene and the tetM gene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the N. gonorrhoeae multiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to the identification of an international transmission route. This first genomic survey of N. gonorrhoeae isolates collected by ARSP will be used to contextualize prospective surveillance. It highlights the importance of genomic surveillance in the Western Pacific and other endemic regions for understanding the spread of drug-resistant gonorrhoea worldwide.

Genomic Epidemiology of CC30 Methicillin-Resistant Staphylococcus aureus Strains from Argentina Reveals Four Major Clades with Distinctive Genetic Features.

Staphylococcus aureus clonal complex 30 (CC30) has given rise to epidemics worldwide and is one of the most prevalent lineages in Argentina, represented by sequence type 30 methicillin-resistant S. aureus SCCmec type IV (ST30-MRSA-IV). ST30-MRSA-IV has displaced previous prevalent clones in the country and demonstrated increased virulence. Despite the burden of infections caused by ST30-MRSA-IV both in hospitals and in communities in Argentina, no detailed genome-based characterization of this clone is available to date. In this study, we used whole-genome sequencing (WGS) to evaluate the genetic diversity, population structure, and genomic characteristics of 190 CC30-MRSA strains circulating in Argentina between 2004 and 2015. Phylogenetic analysis revealed the existence of 4 major clades: ARG-1 (CC30-MRSA-IVc-spa t012), ARG-2 (ST30-MRSA-IVc-spa t021 related), ARG-3 (ST30-MRSA-IVh/j-spa t021 and related), and ARG-4 (CC30-MRSA-IVc-spa t019 and related). The clades were characterized by different distributions of antimicrobial resistance determinants, virulence genes, and mobile genetic elements (MGEs). While ARG-1 and ARG-4 were related to global epidemic MRSA-16 (EMRSA-16) and South West Pacific (SWP) clones, respectively, ARG-3 was phylogenetically distinct from previously defined CC30 epidemic clones. ARG-4, the most prevalent and geographically disseminated in the collection (N = 164), was characterized by specific MGEs and chromosomal mutations that might have contributed to its virulence and success. To our knowledge, this is the first genomic epidemiology study of CC30-MRSA in Argentina, which will serve as baseline genomic data going forward to inform public health measures for infection prevention and control.IMPORTANCE The rise in prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is of public health concern. In Argentina, several studies documented a shift in the epidemiology of CA-MRSA since 2009, with clonal complex 30 (CC30) and, in particular, sequence type 30 MRSA SCCmec type IV (ST30-MRSA-IV) replacing other clones both in communities and in hospitals and possibly displaying increased virulence. By sequencing the whole genomes of 190 CC30 MRSA isolates recovered from Argentina between 2005 and 2015, we showed that they represented a diverse population composed of 4 major clades. The predominant clade evolved from the South West Pacific clone but has acquired a distinct repertoire of mobile genetic elements, virulence genes, and chromosomal mutations that might play a role in its success. Our work is the first extensive genomic study of CC30 S. aureus in Argentina and will contribute not only to the development of genomic surveillance in the region but also to our understanding of the global epidemiology of this pathogen.

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.

The natural history of conjunctival naevi in children and adolescents.

OBJECTIVE: The objective of this study is to characterise the natural history of conjunctival naevi in a paediatric and adolescent population. METHODS: All children and adolescents referred to Moorfields Ocular Oncology Service for evaluation between January 2015 and 2020 were included. Exclusion criteria included age >20 years old and lack of anterior segment photographs. A total of 77 patients were included with a mean age of 12 years (standard deviation: 3.9; range, 4-20). The main outcome measures were: number of conjunctival naevi that grew, changed in pigmentation, required excisional biopsy, or were histologically malignant. If there was growth, the percentage increase in size was measured. RESULTS: At their first visit, 13% of patients (10/77) were discharged to local follow-up and 10% (8/77) proceeded to excisional biopsy, four further patients underwent excisional biopsy after a period of follow-up. On histopathological assessment, 92% (11/12) of lesions were benign conjunctival naevi. One patient, who had suspicious clinical features at presentation, had conjunctival melanoma. Fifty-nine patients were followed over a median of 1.1 years (interquartile range: 1.54; range, 3 months to 4 years). Eight per cent (5/59) of conjunctival naevi enlarged in diameter by a mean percentage increase in size of 2%, whereas 5% (3/59) showed increased pigmentation and 8.5% (5/59) showed decreased pigmentation. CONCLUSIONS: Growth of conjunctival naevi in children is infrequent (8%) and the large majority of those excised are benign. Because of a lack of evidence, these patients are often followed for years in ophthalmic practice. This series demonstrates that prolonged follow-up may not be necessary.

Long-term Outcomes of Small Pigmented Choroidal Melanoma Treated with Primary Photodynamic Therapy.

PURPOSE: To report the long-term outcomes of patients with small, pigmented, posteriorly located choroidal melanoma undergoing primary treatment using photodynamic therapy (PDT) with verteporfin at the London Ocular Oncology Service. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: All patients undergoing primary treatment using PDT with verteporfin from April 2014 to December 2015 and followed until December 2019. METHODS: This is a long-term follow-up study of the same cohort of patients previously reported by our group in 2017 and 2018. MAIN OUTCOME MEASURES: Local tumor control, visual outcomes, and metastasis-free survival. RESULTS: Twenty-six patients were included with a mean (± standard deviation) age and tumor thickness of 62 ± 14 years and 1.3 ± 0.5 mm, respectively. Tumors were posteriorly located (mean distance to optic nerve and fovea = 2.0 ± 2.2 mm and 1.6 ± 1.5 mm, respectively), and the majority were fully pigmented (73%). Overall, patients were followed for a median (interquartile range [IQR], range) of 49.5 (15.3, 7.0-66.0) months from first PDT to last follow-up. Over the course of this study, 14 of 26 (54%) have developed a local recurrence at a median of 20.0 months (20.5, 4.7-60.9 months). The most common pattern of recurrence was an isolated increase in basal dimensions (9/14; 64%). Median (IQR) final logarithm of the minimum angle of resolution visual acuity of the whole cohort was 0.2 (0.5). The only statistically significant difference in baseline and outcome characteristics between treatment failures and nonfailures was the distance to the fovea (median [IQR], 0.5 [1.3] vs. 2.5 [2.8]; P = 0.002) and final logarithm of the minimum angle of resolution visual acuity (median [IQR], 0.50 [0.80] vs. 0.00 [0.14]; P = 0.002), respectively. CONCLUSIONS: Although treatment of small pigmented posterior choroidal melanoma with PDT effectively preserves visual acuity, 5-year treatment-success calculated by Kaplan-Meier analysis was only 38.4%. Recurrences after PDT tend to occur along the tumor edges, often with minimal increase in thickness. Given the substantial risk of treatment failure, primary PDT with vertepofrin is recommended in exceptional cases of choroidal melanoma, for which other treatments with greater tumor control are not a feasible option.

Ultra-wide-field imaging assessment of small choroidal pigmented lesions using red and green colour channels.

BACKGROUND: Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma. METHODS: Retrospective cross-sectional study of patients with small choroidal pigmented lesions up to 3 mm in thickness. All patients underwent clinical and imaging assessment including UWF. Lesions were subcategorized based on thickness and lesion type. A qualitative assessment ensued using the red and green channels feature. RESULTS: A total of 152 patients were included. Melanotic naevi (76/152,50%) and small choroidal melanomas (55/152,36%) were the predominant types. Thickness was <1 mm in 30% (46/152), 1-2 mm in 46% (70/152) and 2-3 mm in 24% (36/152) of cases. Two distinct imaging patterns were noted: dark on RC/undetectable on GC and dark on RC/light on GC. In melanotic naevi the dark on RC/light on GC pattern was significantly associated with increased tumour thickness (p = 0.006) and the presence of lipofuscin (p < 0.001) suggesting a potential prognostic significance. In small melanomas such an association was not established. The majority of small melanomas manifested a dark on RC/undetectable on GC pattern despite the presence of subretinal fluid and lipofuscin. CONCLUSIONS: UWF imaging of choroidal pigmented tumours with red-green channels revealed two distinct patterns. The dark on RC/light on GC pattern was more common in suspicious melanotic naevi, but not in small melanomas. The use of red-green channels is not a reliable diagnostic tool in the early detection of small melanomas.

Genomic surveillance of Acinetobacter baumannii in the Philippines, 2013-2014.

OBJECTIVE: Acinetobacter baumannii is an opportunistic nosocomial pathogen that has increasingly become resistant to carbapenems worldwide. In the Philippines, rates of carbapenem resistance and multidrug resistance are above 50%. We undertook a genomic study of carbapenem-resistant A. baumannii in the Philippines to characterize the population diversity and antimicrobial resistance mechanisms. METHODS: We sequenced the whole genomes of 117 A. baumannii isolates recovered by 16 hospitals in the Philippines between 2013 and 2014. From the genome sequences, we determined the multilocus sequence type, presence of acquired determinants of antimicrobial resistance and relatedness between isolates. We also compared the phenotypic and genotypic resistance results. RESULTS: Carbapenem resistance was mainly explained by acquisition of the class-D ß-lactamase gene blaOXA-23. The concordance between phenotypic and genotypic resistance to imipenem was 98.15%, and it was 94.97% overall for the seven antibiotics analysed. Twenty-two different sequence types were identified, including 7 novel types. The population was dominated by the high-risk international clone 2 (i.e. clonal complex 92), in particular by ST195 and ST208 and their single locus variants. Using whole-genome sequencing, we identified local clusters representing potentially undetected nosocomial outbreaks, as well as multihospital clusters that indicated interhospital dissemination. Comparison with global genomes suggested that the establishment of carbapenem-resistant international clone 2 in the Philippines is likely the result of clonal expansion and geographical dissemination, and at least partly explained by inadequate hospital infection control and prevention. DISCUSSION: This is the first extensive genomic study of carbapenem-resistant A. baumannii in the Philippines, and it underscores the importance of hospital infection control and prevention measures to contain high-risk clones.

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.

Invasive conjunctival melanoma mimicking ocular surface squamous neoplasia: a case series.

BACKGROUND: Conjunctival melanoma is the second most common conjunctival malignant tumour after squamous cell carcinoma, usually arising from primary acquired melanosis and less commonly from a conjunctival naevus or de novo. We report four cases of conjunctival melanoma masquerading as ocular surface squamous neoplasia. METHODS: Four patients (2 females and 2 males; mean age 60.7 years; range 41-72 years) were referred for suspicious conjunctival lesions. In all cases, the lesions had a perilimbal location, were non-pigmented (cases 1 and 3) or mildly pigmented (cases 2 and 4), had a fleshy (cases 1, 2 and 4) or papillomatous (case 3) appearance and involved the corneal surface. In each case, our main clinical differential diagnosis included conjunctival intraepithelial neoplasia and squamous cell carcinoma. All four patients underwent an excisional biopsy with double freeze-thaw cryotherapy and alcohol keratoepitheliectomy. RESULTS: In all four cases, the histopathological diagnosis was of invasive conjunctival melanoma with extension to the deep surgical margins. Adjuvant therapy consisting of strontium-90 ß radiotherapy (all 4 patients) and topical Mitomicyn C (patient 2) was administered. CONCLUSION: Conjunctival melanoma can clinically resemble ocular surface squamous neoplasia. Clinical impressions therefore need to be confirmed histopathologically.

Circumscribed choroidal haemangioma: Indocyanine green angiography features on scanning laser ophthalmoscopy versus traditional digital fundus photography.

BACKGROUND AND OBJECTIVE: Circumscribed choroidal haemangioma (CCH) has several characteristic clinical and angiographic features. We aimed to compare indocyanine green angiography (ICG) findings of CCH captured on a traditional digital camera system (DCS) to newer scanning laser ophthalmoscopy (SLO) platforms. STUDY DESIGN/MATERIALS AND METHODS: A total of 35 patients over a 10-year period diagnosed with CCH using ICG were included (18 imaged with DCS and 17 with SLO). RESULTS: On early ICG frames, intrinsic vessels were apparent in two-thirds (12/18; 67%) of the DCS group compared with all of eyes in the SLO group (p = 0.020). In addition, at maximal hyperfluorescence, most eyes imaged with DCS had a feathery appearance (16/18; 89%) compared with those in the SLO group which all (17/17; 100%) displayed a granular appearance (p < 0.001). The presence of hot spots at maximal hyperfluorescence was also more common in the SLO group (12/17; 71%) versus the DCS group (0/18; 0%) (p < 0.001). Finally, intrinsic vessels and vascular loops could be identified throughout the entire duration of the ICG in 100% of the SLO cases (17/17) versus only 11% (2/18) of DCS cases (p < 0.001). CONCLUSIONS: The visualization of intrinsic vessels, vascular loops, and "hot spots" in CCH is significantly enhanced with SLO compared with DCS. Many characteristic mid-late angiographic findings of CCH are more optimally visualized on SLO which may negate the need for late frames (>30 min) without compromising diagnostic accuracy.