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The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6 low and IL-10 low cases ( P <0.05), whereas ABCA1-mediated CE was increased in IL-10 high patients ( P =0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6 low (HR 2.13 and 2.97, respectively) and IL-10 low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: This was the first study, to the authors' knowledge, to statistically evaluate the predictive accuracy of Collaborative Ocular Tuberculosis Study (COTS) calculator in guiding initiation of antitubercular therapy (ATT) in patients with clinically suspicious tubercular uveitis (TBU) in an international cohort., Objective: To evaluate the accuracy of a score of 4 or greater on the online COTS calculator in recommending ATT initiation., Design, Setting, and Participants: This study was an evaluation of a diagnostic test or technology. Data input required for the COTS calculator were extracted from the COTS-1 study dataset, which comprised retrospective, observational records of patients with TBU who were monitored for 12 months after treatment. Patients were recruited from international ophthalmic centers. In the absence of a traditional criterion standard, the 12-month treatment response to ATT was used to classify patients as disease positive or negative. The accuracy of clinicians at the ATT decision-making stage in the COTS-1 study was set against COTS calculator scores of 4 or greater. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), precision, recall, and F1 score, were computed. Data collected from January 2004 to December 2014 were analyzed., Exposures: COTS calculator to guide initiation of ATT in patients with TBU., Main Outcomes and Measures: Comparison of accuracy between clinician judgment and the COTS calculator, analyzed at varying scores and further stratified by tuberculosis endemicity., Results: Of the 492 participants (mean [SD] age, 42.3 [19.0] years; 233 male [47.3%]), application of the COTS calculator identified 225 (45.7%) with high or very high probability to start ATT (score = 4 or 5) and 111 (22.5%) with very high probability alone (score = 5). COTS-5 exhibited the highest specificity (88.7%; 95% CI, 81.4%-93.8%) compared with clinician judgment (29.6%; 95% CI, 21.4%-38.8%), and clinician judgment led in sensitivity (95.5%; 95% CI, 92.9%-97.4%) compared with COTS-5 (26%; 95% CI, 21.6%-30.7%). COTS-4 and COTS-5 balanced specificity (64.3%; 95% CI, 54.9%-73.1%) and sensitivity (48.8%; 95% CI, 43.7%-54%). PPV and sensitivity were consistently higher in the endemic group for all 3 tests., Conclusions and Relevance: Results of this diagnostic study suggest that the COTS calculator (score ≥4) was more specific than clinician judgment for ATT initiation. Although clinician judgment is a good first step to identify all potential true positives (with high sensitivity), a second consultation with COTS-5 (with high PPV) may lead to less false positives. This tool, apt for high-prevalence, low-resource settings, recommends ATT more selectively for genuine TBU cases. Large prospective studies are essential to explore potential improvements in the calculator's sensitivity.

Background: Ocular inflammatory events following COVID-19 vaccination have been reported in the adult population., Methods: Multinational case series of patients under the age of 18 diagnosed with ocular inflammatory events within 28 days of COVID-19 vaccination., Results: Twenty individuals were included. The most common event was anterior uveitis ( n  = 8, 40.0%), followed by intermediate uveitis (7 patients, 35%), panuveitis (4 patients, 20%), and posterior uveitis (1 patient, 5%). The event was noticed in the first week after vaccination in 11 patients (55.0%). Twelve patients (60.0%) had a previous history of intraocular inflammatory event. Patients were managed with topical corticosteroids ( n  = 19, 95.0%), oral corticosteroids ( n  = 10, 50.0%), or increased dose of immunosuppressive treatment ( n  = 6, 30.0%). Thirteen patients (65.0%) had a complete resolution of the ocular event without complications. All patients had a final visual acuity unaffected or less than three lines of loss., Conclusion: Ocular inflammatory events may happen in the paediatric population following COVID-19 vaccination. Most events were successfully treated, and all showed a good visual outcome.

The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published suspected adverse drug reactions to vaccines against COVID-19. Ocular inflammatory events following COVID-19 vaccination have been reported worldwide., Methods: We analysed MHRA data on spontaneous reports of suspected ocular inflammatory events following COVID-19 vaccination between January 2021 and September 2022., Results: The MHRA received 300 UK spontaneous suspected reports of ocular inflammatory events following COVID-19 vaccination, with a calculated prevalence of 6.6 events per 1 000 000 vaccinated individuals. Anterior uveitis was the most common phenotype (58.3%), followed by optic neuritis in 39.3%. Median number of days between vaccination and onset was 8 days. Resolution of the event was seen in 52.3%., Conclusion: Ocular inflammatory events following COVID-19 vaccination have a very rare prevalence in the UK. There is no increase in the reporting rate of uveitis, optic neuritis and scleritis following COVID-19 vaccination when compared with the range of incidence in the UK population. The Yellow Card System represents a vital instrument within the domain of pharmacovigilance, empowering patients and healthcare professionals to contribute to the ongoing monitoring of medication safety., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To show the role of multimodal imaging in identifying choroidal involvement in acute retinal necrosis (ARN)., Methods: Retrospective case series of ARN patients. Clinical data, including medical history, clinical features and multimodal imaging findings, were collected., Results: Three patients were included. Imaging modalities, such as indocyanine green angiography and optical coherence tomography, were critical in showing choroidal involvement in ARN., Conclusion: Choroidal involvement may occur in ARN along with the well-known retinal features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC., Objective: To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments., Evidence Acquisition: A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC., Evidence Synthesis: From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel., Conclusions: Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients., Patient Summary: Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To describe a challenging case of acute retinal necrosis., Methods: Clinical data, including medical history, clinical findings and imaging features were retrospectively collected in a 28-year-old female with unilateral active retinitis., Results: The yellowish area of retinitis surrounding a pigmented chorioretinal scar and the full thickness retinal hyper-reflectivity associated with diffuse increase in choroidal demonstrated a challenging case of necrotising retinitis, where baseline clinical and tomographic features were atypical and misleading towards a toxoplasmic aetiology. The detection of virus genome in ocular samples was necessary to achieve a correct diagnosis of acute retinal necrosis., Conclusion: Although rare, choroidal involvement may occur in acute retinal necrosis along with the well-known retinal features.

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% of female breast cancer cases are HER2-positive, with the majority being HR-positive. These tumors show a cross-talk between the hormonal and HER2 pathways; the interaction has implications for the treatment options for the disease. In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer.

Cisplatin remains a valid option in muscle-invasive or metastatic urothelial carcinoma, and is even more efficient when nivolumab is added. The well-known side-effect profile and the limited number of treatment cycles represent great advantages over modern drug combinations such as enfortumab-vedotin plus pembrolizumab., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide., Methods: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used., Results: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints., Conclusions: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Aims: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide., Methods: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform., Results: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts)., Conclusions: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Hypotony is a well-recognised, sight-threatening complication of uveitis. It can also be the final common endpoint for a multitude of disease entities. Multiple mechanisms underlie hypotony, and meticulous clinical history alongside ocular phenotyping is necessary for choosing the best intervention and therapeutic management. In this narrative review, a comprehensive overview of medical and surgical treatment options for the management of non-surgically induced hypotony is provided. Management of ocular hypotony relies on the knowledge of the aetiology and mechanisms involved. An understanding of disease trajectory is vital to properly educate patients. Both anatomical and functional outcomes depend on the underlying pathophysiology and choice of treatment., Competing Interests: Competing interests: The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs)., Methods: We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion., Results: Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85)., Conclusion: The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs., (© 2023. The Author(s).)

Introduction: Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide, affecting individuals acrossdifferent age groups. The key to reducing vision loss includes prompt diagnosis and treatment. However, despite the prevalence of ocular toxoplasmosis, there has been little consensus regarding its pathophysiology,clinical features, diagnosis, and especially management., Methods: The data sources were literature reviews, including Pub Med and Medline databases. Search terms included toxoplasmosis, retinitis, vasculitis, vitritis, uveitis alone or in combination with, serum, aqueous, vitreous eye, ocular and review., Results: In this review paper, we have sought to provide an overview of the pathophysiology, epidemiology, and clinical features of the disease, both based on current literature and our own clinical experience. We have also discussed the use of serology, ocular fluid, and ophthalmic investigations that could further facilitate the diagnosis of ocular toxoplasmosis.Different management strategies have been reported worldwide, including newer approaches such as local therapy., Conclusion: A better understanding of critical aspects of ocular toxoplasmosis will hopefully lead to reduced morbidity, including blindness associated with this condition.

Purpose: To describe unusual clinical features and therapeutic management of a case of cytomegalovirus (CMV) ocular disease in a patient on immunomodulatory therapy., Setting/venue: Moorfields Eye Hospital NHS Foundation Trust, London, UK., Methods: Medical history, clinical findings, investigation results, and multimodal imaging were retrospectively collected., Results: A 61-year-old, South-East Asian man, developed CMV-related endotheliitis and occlusive retinal vasculitis, diagnosed by wide-angle fluorescein angiography. No retinitis was present on the fundus examination. Suspicion of CMV etiology was based on anterior segment findings, especially the presence of coin-shaped endothelial lesions. The diagnosis was confirmed by aqueous polymerase chain reaction (PCR) analysis which was positive for CMV DNA. The combined use of topical and systemic valganciclovir resulted in significant improvement of the picture., Conclusions: CMV can manifest in the eye as occlusive retinal vasculitis without the presence of typical retinitis., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Over the past two decades, advancements in imaging modalities have significantly evolved the diagnosis and management of retinal diseases. Through these novel platforms, we have developed a deeper understanding of the anatomy of the choroidal vasculature and the choriocapillaris. The recently developed tools such as optical coherence tomography (OCT) and OCT angiography (OCTA) have helped elucidate the pathological mechanisms of several posterior segment diseases. In this review, we have explained the anatomy of the choriocapillaris and its close relationship to the outer retina and retinal pigment epithelium., Methods: A comprehensive search of medical literature was performed through the Medline/PubMed database using search terms: choriocapillaris, choroid, quantification, biomarkers, diabetic retinopathy, age-related macular degeneration, choroidal blood flow, mean blur rate, flow deficit, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, indocyanine green angiography, OCTA, Doppler imaging, uveitis, choroiditis, white dot syndrome, tubercular serpiginous-like choroiditis, choroidal granuloma, pachychoroid, toxoplasmosis, central serous chorioretinopathy, multifocal choroiditis, choroidal neovascularization, choroidal thickness, choroidal vascularity index, choroidal vascular density, and choroidal blood supply. The search terms were used either independently or combined with choriocapillaris/choroid., Results: The imaging techniques which are used to qualitatively and quantitatively analyze choriocapillaris are described. The pathological alterations in the choriocapillaris in an array of conditions such as diabetes mellitus, age-related macular degeneration, pachychoroid spectrum of diseases, and inflammatory disorders have been comprehensively reviewed. The future directions in the study of choriocapillaris have also been discussed., Conclusion: The development of imaging tools such as OCT and OCTA has dramatically improved the assessment of choriocapillaris in health and disease. The choriocapillaris can be delineated from the stromal choroid using the OCT and quantified by manual or automated methods. However, these techniques have inherent limitations due to the lack of an anatomical distinction between the choriocapillaris and the stromal choroid, which can be overcome with the use of predefined segmentation slabs on OCT and OCTA. These segmentation slabs help in standardizing the choriocapillaris imaging and obtain repeatable measurements in various conditions such as diabetic retinopathy, age-related macular degeneration, pachychoroid spectrum, and ocular inflammations. Additionally, Doppler imaging has also been effectively used to evaluate the choroidal blood flow and quantifying the choriocapillaris and establishing its role in the pathogenesis of various retinochoroidal diseases. As tremendous technological advancements such as wide-field and ultra-wide field imaging take place, there will be a significant improvement in the ease and accuracy of quantifying the choriocapillaris.

Objective: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB)., Method: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator., Results: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT., Conclusion: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To describe clinical features and therapeutic management of a case of isolated subretinal abscess (SRA) in an immunocompetent male patient with no predisposing conditions or risk factors., Methods: Clinical data, including medical history, clinical findings and results of systemic investigations, were retrospectively collected in a 40-year-old man diagnosed with unilateral focal SRA., Results: Systemic investigations did not reveal any extraocular infective focus. Prompt diagnosis of SRA and aggressive systemic antibiotic treatment averted breakthrough into the vitreous cavity and led to clinical resolution with preservation of visual acuity. No local recurrences or distal spread of the infection were found at follow-up., Conclusions: In isolated SRA, timely systemic antibiotic treatment can lead to an excellent clinical outcome. Close monitoring is essential to prevent potential progression of SRA to a sight-threatening endophthalmitis, which would prompt an urgent shift in the therapeutic approach.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Urothelial carcinoma (UC) is the most frequent malignancy of the urinary tract, which consists of bladder cancer (BC) for 90%, while 5% to 10%, of urinary tract UC (UTUC). BC and UTUC are characterized by distinct phenotypical and genotypical features as well as specific gene- and protein- expression profiles, which result in a diverse natural history of the tumor. With respect to BC, UTUC tends to be diagnosed in a later stage and displays poorer clinical outcome. In the present review, we seek to highlight the individuality of UTUC from a biological, immunological, genetic-molecular, and clinical standpoint, also reporting the most recent evidence on UTUC treatment. In this regard, while the role of surgery in nonmetastatic UTUC is undebated, solid data on adjuvant or neoadjuvant chemotherapy are still an unmet need, not permitting a definite paradigm shift in the standard treatment. In advanced setting, evidence is mainly based on BC literature and retrospective studies and confirms platinum-based combination regimens as bedrock of first-line treatment. Recently, immunotherapy and target therapy are gaining a foothold in the treatment of metastatic disease, with pembrolizumab and atezolizumab showing encouraging results in combination with chemotherapy as a first-line strategy. Moreover, atezolizumab performed well as a maintenance treatment, while pembrolizumab as a single agent achieved promising outcomes in second-line setting. Regarding the target therapy, erdafitinib, a fibroblast growth factor receptor inhibitor, and enfortumab vedotin, an antibody-drug conjugate, proved to have a strong antitumor property, likely due to the distinctive immune-genetic background of UTUC. In this context, great efforts have been addressed to uncover the biological, immunological, and clinical grounds in UTUC patients in order to achieve a personalized treatment.

Purpose: To review the literature on endogenous subretinal abscess (SRA)., Methods: We searched in the literature for the terms 'subretinal abscess', 'chorio-retinal abscess' and 'choroidal abscess'., Results: A total of 122 patients were identified, of whom 20 patients (22 eyes) had no identified systemic infective foci (group 1) and 102 (120 eyes) had systemic infective foci (group 2). The mean age for group 1 was 44.6 years (range 2 weeks-82 years) and for group 2 was 43.2 years (range 1-89 years). The responsible pathogen was identified in 90% and 95% of cases, respectively. In group 1 the most frequent causative agents were Aspergillus and Nocardia, while in group 2 were Nocardia, Mycobacterium Tuberculosis and Klebsiella. In both groups the most common symptoms were reduced vision (70% and 72.5%, respectively), pain (65% and 29.4%, respectively) and redness (35% and 17.6%, respectively). For group 1 there was no difference between mean initial and final visual acuity (1.7 logMAR, range 0-3 logMAR), while for group 2 mean initial and final visual acuities were 0.8 logMAR and 0.6 logMAR, respectively. Final visual acuity was significantly better in group 2 (p = 0.003). Anterior segment inflammation was seen in 77.3% of cases of group 1 and 66.7% of cases of group 2. In both groups the abscess most common locations were posterior pole (45.4% and 32.5%, respectively) and temporal periphery (13.6% and 13.3%, respectively). Clinical features included hemorrhages (76.5% and 76.3%, respectively) and subretinal fluid (75% in both groups). Diabetes mellitus (20% and 25.5%) and immunosuppressive drug intake (35% and 23.5%) were the main predisposing factors for SRA. Combination of systemic and intravitreal antibiotics/antifungals and vitrectomy was the main therapeutic strategy for both groups. Systemic treatment alone was used mainly for cases of tubercular etiology. The timing of vitrectomy differed between the two groups, as it more commonly followed the use of systemic and intravitreal antibiotics in the forms associated with systemic infective foci. Additional abscess drainage or intralesional antibiotics were performed in 23.8% of cases., Conclusion: At present no guideline exists for the treatment of subretinal abscess. Systemic broad-spectrum antibiotic treatment is of primary importance and should be used in all cases unless contraindicated. Combination of systemic and local treatment is the most frequently adopted strategy., (© 2022. The Author(s).)

Purpose: To report a case of exuberant anterior chamber inflammation post partial removal of supramid® stent., Methods: Case report., Results: The sudden intraocular pressure drop induced by partial removal of ripcord suture from a glaucoma drainage device can result in blood-retinal and blood-aqueous barrier breakdown, inducing uveitis., Conclusions: Intensive inflammatory prophylaxis prior to maneuvers to reduce intraocular pressure may reduce the risk of severe intraocular inflammation in patients with a previous history of uveitis as a consequence of sudden hypotony.

Objective: To investigate the concordance between aqueous and vitreous tap culture results among different types of bacterial endophthalmitis., Methods and Analysis: This retrospective cohort analysis included all cases diagnosed with endophthalmitis at Moorfields Eye Hospital between January 2008 and March 2020. Aqueous and vitreous samples obtained simultaneously at presentation. Samples were evaluated for sensitivity, specificity, negative and positive predictive values., Results: A total of 217 patients (217 eyes) were included in the study. Postsurgical endophthalmitis was the most common type of endophthalmitis and diagnosed in 35.9% of the cases. The rate of positive culture results was 32.2% from vitreous tap and 21.7% from aqueous tap. The culture yield through vitreous sampling was 15.7% when aqueous culture results were negative, and in 5.1%, the aqueous sample was positive when the vitreous tap results were negative. Considering the vitreous tap as the gold standard, aqueous sample culture results showed a statistically significant high specificity and positive predictive values in cases of postsurgical endophthalmitis, late-onset endophthalmitis associated with glaucoma procedures, postintravitreal injection and endophthalmitis associated with bacterial keratitis. Coagulase Negative Staphylococcus was the most common organism isolated from vitreous and aqueous samples., Conclusions: Even though the sensitivity and specificity of aqueous tap are low, our results show that in a few cases it identified important organisms, otherwise missed by vitreous sampling alone. Culture of vitreous sample remains the gold standard for isolation of pathogen in bacterial endophthalmitis, but aqueous samples should also be obtained as an adjunct for the diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report treatment outcomes and efficacy of the fluocinolone acetonide 0.19 mg intravitreal implant (Iluvien) in controlling retinal and choroidal inflammation in 11 patients with birdshot retinochoroiditis., Methods: A single-centre, retrospective, interventional case series. The primary efficacy end point was improvement in vascular leakage on fluorescein angiography (FA), effect on cystoid macular oedema (CMO) and resolution of hypofluorescent lesions on indocyanine green angiography (ICGA); secondary measures were improvements on pattern and full-field electroretinogram (PERG; ERG) parameters. Safety outcome measures were intraocular elevation and cataractogenesis., Results: Fifteen eyes received Iluvien implant with an average follow-up of 31 months (range 12-36 months). Prior to the implant, 5 (33.3%) eyes had received dexamethasone intravitreal implant 0.7 mg (Ozurdex). FA showed evidence of vascular leakage in all eyes at baseline. Between month 6 and 12, FA showed that 73.4% of eyes had no leakage, this increased to 84.6% by month 24. Three eyes in our study had CMO at baseline. 6 months after Iluvien implant, all eyes achieved complete CMO resolution. One year after insertion of the implant, the characteristic hypofluorescent lesions on ICGA were unchanged in all cases. There was baseline ERG evidence indicating a high incidence of peripheral cone system dysfunction and most showed PERG evidence of macular dysfunction. Retinal function improved and macular function improved or was stable in the majority following treatment., Conclusions: The results show the possible therapeutic effect of Iluvien in the management of Birdshot-related vascular leakage, CMO and retinal dysfunction. However, choroidal lesions seem to persist with no detectable response to treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine's immunogenicity and safety, especially in patients with pre-existing inflammatory conditions., Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021., Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19-84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1-14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%)., Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome., (© 2021. The Author(s).)

Purpose: To explore the all-cause mortality in patients with acquired immune deficiency syndrome (AIDS) and Cytomegalovirus (CMV) retinitis., Methods: A retrospective cohort study of patients with CMV retinitis (CMVR) presented to a tertiary referral center in Singapore from January 1, 2004, through December 31, 2015., Results: A total of 144 patients were studied (87 survived, 11 lost to follow up, 46 died). Patients with bilateral CMVR and six-month follow up CD4 + T cell count < 50 cells/mm 3 have shorter time to mortality, compared to patients with CD4 + T cell count > 50 cells/mm 3 ( p < .001) and unilateral disease ( p = .043). Baseline CD4 + T cell count, size and zone of initial primary retinitis lesions, recurrences of retinitis, and timing of combined antiretroviral therapy (cART) are not significantly associated with mortality., Conclusion: Bilateral ocular involvement and lack of immune recovery in patients with AIDS and CMVR are associated with shorter survival time.

Background: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory eye disease, affecting the inner choroid and the outer retina. Recent advances in multimodal imaging have been important in the understanding of the pathophysiology of the disease, allowing a better characterization of the morphology of this condition., Methods: Narrative review., Results: In this review, a comprehensive overview of clinical features, imaging findings, treatment management, and long-term outcomes of patients with APMPPE will be provided., Conclusions: Although APMPPE was originally believed to be a self-limited condition with a good prognosis, the disease can be recurrent and result in significant loss of vision function. Fundus imaging plays an important role in the diagnosis and management of the disease, allowing to evaluate response to treatment and onset of complications., (© 2021. The Author(s).)

Purpose: To provide a comprehensive overview of choroidal involvement in non-infectious posterior scleritis; including different imaging modalities and their clinical usefulness., Methods: Narrative review., Results: Posterior scleritis is an uncommon yet potentially sight-threatening inflammation of the sclera. During the disease process, inflammation can spread to the adjacent choroid, causing different manifestations of choroidal involvement: (1) increased choroidal thickness, (2) choroidal vasculitis, (3) presentation as a choroidal or subretinal mass in nodular posterior scleritis, and (4) choroidal folds, choroidal effusion and exudative retinal detachment., Conclusions: Clinical characteristics and multimodal imaging can aid in diagnosing and monitoring disease progression and response to treatment in non-infectious posterior scleritis with choroidal involvement., (© 2021. The Author(s).)

White dot syndromes (WDS) represent a heterogeneous group of inflammatory diseases, primarily affecting the outer retina, choriocapillaris and choroid. Recent advances in the field of ocular imaging and development of new technologies, including optical coherence tomography angiography (OCT-A), have allowed a better characterization of the morphology of these conditions. This review will analyse the WDS from an imaging-based perspective, providing a better understanding of the pathophysiology underlying these disorders., (© 2021. The Author(s).)

Systemic corticosteroids and immunosuppressant agents are the mainstay of therapy for non-infectious uveitis (NIU). However, the risks associated with systemic administration and the need of delivering an effective and safe anti-inflammatory treatment targeted to the site of inflammation have prompt the use of local therapy in the management of NIU. This review will analyse the different local treatment options available, including corticosteroids, anti-vascular endothelial growth factor (VEGF), methotrexate and the recent biologics., (© 2021. The Author(s).)

Purpose: The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse effects after COVID-19 vaccinations have emerged. This review summarizes ocular adverse effects possibly associated with COVID-19 vaccination, and discusses their clinical characteristics and management., Methods: Narrative Literature Review., Results: Ocular adverse effects of COVID-19 vaccinations include facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves' Disease. Studies in current literature are primarily retrospective case series or isolated case reports - these are inherently weak in establishing association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of the COVID-19 disease itself. Hence, we hypothesize that the human body's immune response to COVID-19 vaccinations may be involved in the pathogenesis of the ocular adverse effects post-COVID-19 vaccination., Conclusion: Ophthalmologists and generalists should be aware of the possible, albeit rare, ocular adverse effects after COVID-19 vaccination.

Background: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged., Methods: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine., Results: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups., Conclusion: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose : To analyze choroidal angioarchitecture in sympathetic ophthalmia (SO) using swept-source optical coherence tomography (SS-OCT) images. Methods : Case-control study of six patients with SO. Qualitative changes and quantitative parameters, including choroidal thickness (CT) and choroidal vascularity index (CVI), were analyzed. Results : Qualitative findings in the acute phase of SO on SS-OCT included retinal serous detachment with hyperreflective septa, choroidal folds, alterations in angioarchitecture with loss of vascular lacunae, and Dalen-Fuchs nodules. There was significantly higher CT in SO (284.05 ± 24.12 µm) compared to healthy controls (229.57 ± 46.67 µm, p = 0.04) and also increased CVI in SO (62.06 ± 2.07% vs 56.79 ± 3.15%, p = 0.006). Conclusions : CVI was significantly increased in SO, representing a novel noninvasive biomarker of disease activity. SS-OCT provides a useful qualitative and quantitative parameter, which can be potentially explored in the diagnosis and monitoring of patients with SO.

Topic: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis., Clinical Relevance: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU., Methods: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process., Results: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis., Discussion: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Topic: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU)., Clinical Relevance: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition., Methods: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process., Results: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive., Discussion: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Unclear pathogenic mechanisms underlying the ocular tuberculosis (OTB) has resulted in perplexity related to the diagnosis and management of the disease. Developments in experimental research and innovations in molecular diagnostics have recently provided a new understanding of disease pathogenesis and natural history. The current review focuses on the new insights into OTB pathogenesis, derived from in vivo and in vitro studies on Mycobacterium tuberculosis dissemination and localization into the eye, in combination with histopathological studies on chorioretinal tissue and vascular network. Advances in the knowledge of OTB have influenced disease management in the clinical setting and lead to reconsideration of the role of existing treatments and suggesting potential new therapeutic approaches., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Ocular tuberculosis has protean clinical manifestations. Because of its varied clinical presentation, multimodal imaging is very important to characterize the disease activity, presence of inflammation, determining therapeutic response, and detection of complications., Methods: Narrative review., Results: In this review, various imaging modalities employed in the management of ocular tuberculosis including fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) have been reviewed. Not only do these imaging tools complement each other in providing a comprehensive assessment of the pathology, they also help in gaining valuable insights regarding the evolution of the disease., Conclusions: Fundus imaging plays a vital role in the diagnosis and management of patients with posterior uveitis due to tuberculosis. Fundus imaging may have a useful role in defining clinical endpoints for ocular tuberculosis in the future.

Purpose : To report a novel peripheral finding in patients with Birdshot retinochoroiditis (BRC) using ultra-widefield fluorescein angiography (UWFFA). Methods : UWFFA images from 90 patients diagnosed with BRC were reviewed. All images were evaluated for the presence of peripheral retinal ischemic changes and ischemia-related complications. Findings : Thirty-six eyes of 24 patients showed features of peripheral ischemia, including 18 eyes with peripheral capillary non-perfusion (CNP), 5 eyes with teleangectasias, with or without microaneurysms, and 13 eyes with both teleangectasias and CNP. None of the 36 eyes with peripheral ischemic changes developed retinal neovascularization following the diagnosis of peripheral ischemia. Conclusions : Peripheral ischemia may present in eyes with chronic inflammation as seen in BRC but does not seem to progress to neovascular complications. This is likely to be more common than suspected and has now become evident following the advent of UWFFA. Abbreviations : HLA-A29: Human leukocyte antigen - A29; FFA: Fundus fluorescein angiography; OCT: Optical coherence tomography; ICGA: Indocyanine green angiography; UWF: Ultra-wide field; UWFFA: Ultra-wide field fluorescein angiography; CNP: Capillary non-perfusion.