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International audience; An improvement in the catalytic enantioselective allylboration of isatins with 2-allyl-1,3,2-dioxaborolane in the presence of chiral BINOL derivatives is reported, offering an efficient one-step access to enantioenriched N-unprotected 3-allyl-3-hydroxy-2-oxindoles. This catalytic process is also effective for the crotylboration reaction with enantiomeric ratios (er) up to 97:3, as well as for the asymmetric synthesis of homopropargylic alcohols via an allenyl addition to indoline-2,3-diones. Origins of the high enantioselectivity in chiral BINOL-catalyzed allylboration of isatins were examined by DFT calculations. A hypothetical scenario suggested a crucial internal hydrogen bonding between the amide group (C═O···H-O) and the ethylene hydroxyl of the transient chiral mixed boronate ester, generating a rigid and stabilized system that favors the addition of the allylboron species to the Re face of the ketone function. The key role of the alcohol additive (t-BuOH or t-AmOH) in the enantioselective allylboration reaction of isatins has also been shown on the basis of a kinetics study and computational calculations by favoring the transesterification of the 2-allyl-1,3,2-dioxaborolane with BINOL via proton transfer processes.

Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.

Purpose Radiation maculopathy (RM) is the leading cause of visual acuity (VA) loss after proton beam therapy (PBT) of choroidal melanoma. The aim of this study was to assess the value of optical coherence tomography-angiography (OCT-A) for the diagnosis of RM in patients with choroidal melanoma treated with PBT. Materials & methods This 2-year prospective, descriptive, single-center study included patients treated with PBT for choroidal melanoma. VA measurement, retinography, OCT and OCT-A were performed. Vascular density (VD) in the superficial capillary plexus (SCP), peri-foveal anastomotic ring changes and foveal avascular zone (FAZ) enlargement were studied. Results Nineteen patients were included in the study. The median baseline melanoma thickness was 5.7 [3.6–8.1] mm. The median melanoma-to-macula distance was 3.5 [2.6–4.6] mm. The earliest signs of RM identified on retinography were hard exudates developing at 12 [12–24] months, followed by retinal hemorrhages at 18 [12–30] months, found in 88.9% and 77.8% of patients respectively. On OCT, the earliest sign was the onset/progression of cystoid macular edema (CME) at 12 [6–12] months, found in 10 patients (52.6%). On OCT-A, 100% of patients presented with a discontinuity of the perifoveal anastomotic ring and a FAZ enlargement after 12 [6–24] months. After 12 months, a VD loss in the SCP by 11.7% and 10.8% compared to baseline, was found in the macular and foveal areas respectively. A significant negative correlation was found between the VA and the VD in the macular SCP (R = −0.43; p = 0.029). Conclusion OCT-A is a reliable and effective diagnostic tool for RM in patients with choroidal melanoma treated with PBT.

Reconstruction of the posterior lamella after eyelid tumor removal is challenging and not consensual. Tarsus is the most suitable graft, but is only available in small amounts. Herein, we aim to determine the most appropriate way to replace the tarsus by comparing the biomechanical, histological, and optical properties of five commonly used grafts.This study was conducted at the University hospital of Nice between June 2019 and June 2020. Five posterior lamella grafts (tarsus, conchal cartilage, sclera, hard palate, and dermis) were harvested in five fresh frozen cadavers. Biomechanical properties were assessed by tractometry. Collagen and elastin fibers were analyzed by using histological analysis and optical characterization with the second harmonic generation imaging.The mean Young's modulus was 8.92 MPa (range, 2.90-22.90 MPa), 1.05 MPa (range, 0.39-1.76 MPa), 8.72 MPa (range, 2.0-23.50 MPa), 2.57 MPa (range, 0.41-4.35 MPa), and 1.44 MPa (range, 0.71-2.30 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The mean tensile strength was 3 MPa (range, 1.70-6.88 MPa), 0.54 MPa (range, 0.13-0.79 MPa), 2.87 MPa (range, 1.23-5.40 MPa), 1.4 MPa (range, 0.21-2.40 MPa) and 1.0 MPa (range, 0.46-1.43 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. Hard palate mucosa was the closest to the tarsus regarding the ratio of elastin and collagen fibers. The average second harmonic generation intensity was 221 arbitrary units (a.u.) (range, 165-362 a.u.), 182 a.u. (range, 35-259 a.u.), 369 a.u. (range, 206-533 a.u.), 108 a.u. (range, 34-208 a.u.), and 244 a.u. (range, 195-388 a.u.) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The hard palate mucosa and the dermis were the closest to the tarsus regarding the collagen fiber size and orientation, respectively.By attributing 2 points for each characteristic (biomechanical, histological, and optical), the hard palate mucosa and the sclera seem to be the most suitable grafts to replace the tarsus.The aim of this article was to assess the biomechanical, histological and optical characteristics of five of the most commonly used tarsal grafts; this may be helpful in decisions for clinical practice.

We aimed to assess the efficacy and safety of a standardized hyperbaric oxygen (HBO2) therapy protocol in patients with retinal artery occlusion (RAO).A retrospective study was conducted in our tertiary care center from July 2016 to September 2019. Patients experiencing central RAO and branch RAO for less than seven days were included. Once the diagnosis was made, patients were urgently referred to the HBO2 department to receive a first 90-minute HBO2 session at a pressure of 2.5 ATA. Patients underwent two daily sessions seven days a week for at least 15 days. If no reperfusion was seen on fluorescein angiography on Day 15, treatment was continued for an additional week with an assessment on Day 21. The primary endpoint was BCVA improvement defined as a decrease by 0.3 logMAR at one month.Twenty-eight patients were included during the study period. Fifty-seven percent of patients were treated more than 12 hours after the onset of the first symptoms. The mean BCVA was 1.5 logMAR at the time of referral and improved to 0.9 logMAR after HBO2 (p=0.001). A multivariate analysis identified a high blood pressure (p=0.039) and a low initial BCVA (p=0.005) as poor prognostic factors.Performing HBO2 sessions twice daily at a pressure of 2.5 ATA appears to be an effective and safe treatment for RAO.

Purpose To compare the effect of antiseptics and antibiotics on the occurrence of Infectious Keratitis (IK) secondary to Corneal Foreign Body (CFB) removal. Methods Multicenter retrospective study conducted between June 2020 and June 2022 in patients referred for CFBs and treated with Picloxydine (Group 1) or Tobramycin (Group 2) for 7 days. A follow-up visit was scheduled on Day 3 (D3) and a phone call on D30. The primary outcome measure was the occurrence of IK. Results 307 patients (300 men) with a mean age of 42.8 (14.8) years were included. The mean (SD) time to consultation was 43.1 (45.6) hours. Picloxydine and Tobramycin were given to 155 and 152 patients. Half of patients (n = 154, 50.2%) were building workers and 209 (68.1%) did not wear eye protections. CFBs were mainly metallic (n = 292, 95.1%). Upon referral, rust was found in 220 patients (72.1%). A burr was used in 119 (38.9%) patients. IK occurred in 15 (4.9%) patients, 8 (5.3%) in Group 1 and 7 (4.5%) in Group 2 (p = 0.797). IK was successfully treated in all cases. Persistent rust was found in 113 patients (36.9%) on D3 without difference between burr or needle use (p = 0.278). On D3, corneal healing was delayed in 154 patients (47.2%), mainly in burr-treated patients (p = 0.003). The mean (SD) work stoppage duration was 0.32 (0.98) days. Conclusion IK rate was 4.9%. The efficacy of antibiotics and antiseptics was similar on CFB removal. Using a burr was associated with a longer healing time. CFBs had a limited social impact.

International audience

Graft-versus-host disease (GVHD) is a common complication in patients undergoing allogeneic stem cell transplantation for acute myeloblastic leukemia that could be very difficult to treat. Lifitegrast 5% (Xiidra@, Novartis), a new immunosuppressive eye drop, was recently approved by the FDA for the treatment of severe dry eye and is currently under review by the European Medicines Agency. In France, lifitegrast has been approved by the French authorities for temporary use in refractory dry eye syndrome resistant to tear substitutes and topical cyclosporine. To date, serious complications have been reported only exceptionally. In this article, we report the case of a 65-year-old patient with a medical history of acute myeloid leukemia (AML) diagnosed in 2015 who received a first matched related donor transplant. In 2019, this patient developed chronic GVH involving the skin, oral mucosa and eye. Despite taking topical and systemic medications for 3 months, the patient did not report relief of ocular symptoms. Therefore, lifitegrast was prescribed. To our knowledge, we report the first case of corneal perforation in which evisceration was required following treatment with topical lifitegrast for chronic GVH. In the case presented here, it can be assumed that the underlying mechanisms leading to corneal perforation are multifactorial. Using drug accountability criteria, lifitegrast appears to be strongly associated with the development of bacterial keratitis and corneal perforation.

Aldol addition of α-triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone), promoted by excess lithium diisopropylamide (LDA), was developed and applied to the synthesis of original C-TIPS diazoaldols, C-TIPS diazoketols, and a related Mannich-type product. An unprecedented mechanistic pathway has been proposed, involving a lithiated triazene intermediate resulting from the nucleophilic addition of LDA on the diazo moiety, supported by experimental results and DFT calculations.

Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second, tissue biopsy is not routinely recommended due to the risk of extraocular dissemination. Third, UM is an aggressive cancer because it is estimated that about 50% of patients will experience metastatic spread without any curative treatment available at this stage. These challenges better explain the two main objectives in the creation of a dedicated UM biobank. First, collecting UM samples is essential due to tissue scarcity. Second, large-scale translational research programs based on stored human samples will help to better determine UM pathogenesis with the aim of identifying new biomarkers, allowing for early diagnosis and new targeted treatment modalities. Other periocular malignancies, such as conjunctival melanomas or orbital malignancies, also raise specific concerns. In this context, the number of biobanks worldwide dedicated to ocular malignancies is very limited. The aims of this article were (i) to describe the specific challenges raised by a dedicated ocular malignancy biobank, (ii) to report our experience in setting up such a biobank, and (iii) to discuss future perspectives in this field.

Resume Les lymphomes sont les pathologies orbitaires malignes de l’adulte les plus frequentes. Parmi eux, le lymphome du manteau est une forme particulierement agressive, souvent decouverte par une atteinte systemique, et dont le pronostic est sombre du fait de recidives frequentes. Cette pathologie decoule d’une translocation chromosomique t(11 ;14)(q13 ;q32) aboutissant a un signal anti-apoptotique via une surexpression de Bcl-2. Son traitement repose actuellement sur une poly-chimiotherapie a base de cytarabine. Nous decrivons ici le cas d’un patient presentant une recidive orbitaire d’un lymphome du manteau traite avec succes par inhibiteur de Bcl-2 par voie orale en monotherapie. Un homme de 58 ans ayant ete traite pour un lymphome du manteau par R-CHOP il y a 8 ans et en remission depuis 5 ans a presente une baisse d’acuite rapidement progressive gauche associee a une diplopie binoculaire. L’examen clinique montrait une baisse d’acuite visuelle gauche a 1/20 Parinaud 20, un deficit pupillaire afferent relatif gauche. L’examen orbito-palpebral montrait une paralysie du VI gauche, une exophtalmie axile de 2 mm indolore ainsi qu’une hypoesthesie dans le territoire du V1 gauche permettant de diagnostiquer un syndrome de l’apex orbitaire gauche. Le champ visuel montrait un elargissement de la tâche aveugle gauche. Un scanner et une IRM realises en urgence montraient une masse tissulaire extra-conique apicale infiltrant le muscle droit median, s’etendant a la fissure orbitaire superieure, au canal optique et au sinus caverneux gauche, en hyper signal T2 et iso signal T1. L’aspect morphologique etait fortement evocateur d’un processus infiltratif lymphomateux. Une tomodensitometrie par emission de positon au 18 FDG (PET FDG) permettait d’identifier la lesion orbitaire mais egalement des hyperfixations pathologiques axillaires et coliques ; compte tenu du tableau clinique et para clinique, le diagnostic de recidive de lymphome du manteau etait pose sans recours a la biopsie. Un traitement par Venetoclax (inhibiteur du Bcl-2), etait debute. A un mois de traitement on constatait une disparition clinique complete du syndrome de l’apex avec remontee de l’acuite visuelle a 8/10 Parinaud 4 et une reponse metabolique complete au PET-Scanner. Le TEP scanner de controle ainsi que l’examen clinique a 3 mois etaient strictement normaux. Lors de la consultation de suivi a un an, le patient etait toujours sous Venetoclax, l’examen clinique etait inchange et le PET-scanner decrivait toujours une reponse metabolique complete.

The NOTCH signaling system regulates a variety of cellular processes during embryonic development and homeostasis maintenance in different tissues and contexts. Hence, dysregulation of NOTCH signaling is associated with a plethora of human cancers, and there have been multiple efforts to target key components of this pathway. In this review, we briefly highlight the latest research advances in understanding HES6, a poorly studied component of the NOTCH pathway. We summarize the role of HES6 in cancers with a focus on uveal melanoma. Finally, we discuss the ongoing efforts to target the NOTCH-HES6 axis in cancers.

Purpose: To study the outcome of latent tubercular uveitis (LTBU) treated with antitubercular therapy (ATT) combined or not with adjuvant systemic corticosteroids. Methods: Twenty patients (27 eyes) with LTBU were included in a monocentric retrospective study and evaluated for the absence of active disease after treatment. Data on the clinical outcomes (active inflammation), vision (best-corrected visual acuity, BCVA) and treatment were collected retrospectively. Results: Fourteen patients received ATT alone and six patients received ATT combined with systemic corticosteroids. The two groups were not comparable in terms of proportion of tubercular panuveitis cases and initial BCVA (59.3 ± 8.2 letters vs 44.2 ± 15.2 letters). There was no significant difference in remission rate and in BCVA between both groups 3 months after ATT discontinuation. Conclusion: Patients with LTBU treated with ATT alone had visual and inflammatory outcomes at least comparable to those of patients treated with ATT combined with systemic corticosteroids.

Purpose: Lower eyelid management is challenging. The conchal cartilage is often considered a spacer of choice for treating lower eyelid retraction. However, dermis graft has also recently been shown to be a viable spacer. The aim of this study was to compare the efficacy of dermis graft to that of conchal cartilage graft in this indication. Methods: A retrospective comparative study was conducted in patients who underwent lower eyelid lengthening with autologous dermis graft (group 1) or autologous conchal cartilage graft (group 2). The main outcome measure was the reduction in inferior scleral show (ISS) assessed by three independent masked surgeons. Secondary outcome measures was the assessment of lagophthalmos and corneal keratitis. Complications were also recorded. Results: Twenty-five eyelids of 23 patients were included: 11 and 14 eyelids, respectively in group 1 (dermis graft) and group 2 (conchal cartilage graft). Patient mean follow-up was 12.3 (±12.5) and 7.1 (±7.7) months, respectively. No statistical differences in postoperative ISS reduction, lagophthalmos and exposure keratitis was observed ( p = 0.540, p = 0.946, p = 0.934, respectively). Three patients experienced a grade I Clavien–Dindo complication in group 1 and one patient experienced a grade II complication in group 2 ( p = 0.540). Conclusion: Autologous dermis grafts and conchal cartilage grafts provide favorable outcomes without major complications.

To assess feelings, preoperative anxiety, and need for information in patients undergoing intravitreal injections (IVI). An observational cross-sectional study was conducted in our tertiary university care center between December 2017 and December 2018. Consecutive patients undergoing IVI were included. A paper survey was completed before and after IVI to assess patient experience. Preoperative anxiety and need for information were assessed using the Amsterdam Preoperative Anxiety Information Scale (APAIS) score. Hundred patients with a median age of 76.5 years (42–95, SD = 10.1) were included. Median best-corrected visual acuity (BCVA) in both eyes was 0.4 logMAR. Main IVI indications were wet age-related macular degeneration (n = 58), diabetic macular edema (n = 19), and venous occlusion (n = 16). The IVI most unpleasant steps were as follows: using an eyelid retractor, needle entry, changing of physician from one IVI to another, the pre-IVI waiting time, and the high number of IVI required for disease control. Preoperative anxiety (APAIS score ≥ 11) was correlated in the multivariate analysis with the need for information (p = 0.004), changing of ophthalmologist between different IVI sessions (p = 0.006), and pain expected before the IVI (p = 0.010). The need for information (APAIS score ≥ 5) was only associated with the preoperative anxiety in the multivariate analysis (p = 0.001). Preoperative anxiety and need for information are common in patients undergoing IVI even after many IVI. Being injected by different practitioners was strongly correlated with preoperative anxiety and should be avoided as much as possible. Better educational and information programs are needed.

The immune reconstitution inflammatory syndrome is a phenomenon typically described in HIV patient during the restoration of CD4 count after highly active antiretroviral therapy. Non-HIV immune reconstitution inflammatory syndrome has also been described after organ transplantation or immune recovery in neutropenic patients. We report the case of a 50-year-old man who presented to our department with left painful proptosis and ophthalmoplegia 2 days after having performed cytapheresis for a mantel cell lymphoma. Systemic work up and biopsy were performed and symptoms were relieved with intravenous steroids therapy. To our knowledge, this is the first case of orbital non-HIV immune reconstitution inflammatory syndrome described in the literature.

Purpose To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. Patients and method A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. Results Twenty-five patients with a mean age of 63.2 years (38–92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6–120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). Conclusion Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered.

PURPOSE To assess the efficacy and safety of bone-anchored dental implant placement at the same time as orbital exenteration compared with delayed implant placement. MATERIALS AND METHODS A retrospective comparative study was conducted in a single tertiary care center between December 2003 and December 2017. Patients who underwent bone-anchored implant placement at the same time as orbital exenteration were included (group 1) and compared with patients who underwent delayed implant placement (group 2). The main outcome was the 1-year success rate of implant osseointegration. The secondary outcomes were the 5-year success rate of osseointegration, postoperative complications, and time between orbital exenteration and prosthesis placement. RESULTS Ten and 11 patients (21 and 22 implants) with a mean follow-up of 50.2 and 48.5 months were included in groups 1 and 2, respectively. Patients in group 1 were significantly older (69.7 vs 61.2 years, P = .026). No significant differences were found between both groups regarding tumor type and location, prior treatments, smoking status, and postoperative radiation beam radiotherapy. The 1- and 5-year success rates of osseointegration were 95.5% and 93.3% in group 1, and 100% and 100% in group 2, respectively (P = .488 and P = .450 between both groups). One implant did not osseointegrate in group 1 due to osteitis. Ethmoidal fistula was the most common postoperative complication found in both groups (P = .670). The mean time between orbital exenteration and episthesis placement was 8 (3 to 14) vs 11 (3 to 15) months in groups 1 and 2, respectively (P = .467). CONCLUSION Placing implants at the same time as orbital exenteration is a viable procedure. It reduces surgical morbidity and allows placement of implants in a nonirradiated area.

Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM., N.J.L. would like to thank all members of the Laboratory of Clinical and Experi-mental Pathology (LPCE), Centre Hospitalier Universitaire de Nice, Nice, France; and all members of the Anatomic Pathology Service, Pathology Department, Centro Hospitalar e Universitario do Porto,Porto, Portugal, especially to JoseRamon Vizcaino (Head of Service), Joana Raposo Alves (Advisor ofPathology Training), Andre Coelho, David Tente and Francisca Emanuel Costa for their continuous support and help in the development

Immune checkpoint inhibitors (ICIs) have dramatically changed the prognosis of advanced melanoma patients, but also exposed them to immune-related adverse events (irAEs).1 Furthermore, with the combination ipilimumab (IPI) plus nivolumab (NIVO) some rare irAEs, such as myositis and neuromuscular diseases, are increasingly emerging.2 Similar manifestations have been reported during coronavirus disease 2019 (COVID-19)3 and more rarely with the vaccination.4 Because cancer patients exhibit severe and fatal forms of the COVID-19 disease, vaccination is recommended.

Purpose. To determine the course and outcomes of cataract surgery in one-eyed patients. Methods. This retrospective cohort study was conducted at the University Hospital of Nice, France. All one-eyed patients who underwent cataract surgery in their functional eye between January 2014 and December 2018 were included. A one-eyed patient was defined as having a visual acuity (VA) ≤20/200 in the other eye. Data were collected from the medical records and included the sociodemographic factors, the past medical history, data from the preoperative and postoperative clinical examinations, the surgical course, and the visual outcomes. Results. One hundred one-eyed patients with a mean age of 74.01 years were included (48 men/52 women). The mean preoperative VA was 20/100 (+0.74 logMAR). The VA ranged between 20/200 and 20/40 in 75 (75%) patients, was >20/40 in 8 (8%), and was p < 0.001 ). Conclusion. A low rate of intraoperative complications was observed in one-eyed patients during cataract surgery. In most cases, a good visual recovery was achieved after cataract surgery, even in patients who experienced a surgical complication.

Simple Summary Managing locally advanced periocular malignant tumours, especially those invading the orbit, is challenging. Orbital exenteration has long been considered the gold standard. The development of conservative surgical techniques in the early 2000s, followed by the emergence of new targeted therapies and immunotherapies over the past decade, has led to a paradigm shift towards the use of ‘eye-sparing’ strategies. Abstract The management of periocular skin malignant tumours is challenging. Surgery remains the mainstay of treatment for localised eyelid cancers. For more locally advanced cancers, especially those invading the orbit, orbital exenteration has long been considered the gold standard; however, it is a highly disfiguring and traumatic surgery. The last two decades have been marked by the emergence of a new paradigm shift towards the use of ‘eye-sparing’ strategies. In the early 2000s, the first step consisted of performing wide conservative eyelid and orbital excisions. Multiple flaps and grafts were needed, as well as adjuvant radiotherapy in selected cases. Although being incredibly attractive, several limitations such as the inability to treat the more posteriorly located orbital lesions, as well as unbearable diplopia, eye pain and even secondary eye loss were identified. Therefore, surgeons should distinguish ‘eye-sparing’ from ‘sight-sparing’ strategies. The second step emerged over the last decade and was based on the development of targeted therapies and immunotherapies. Their advantages include their potential ability to treat almost all tumours, regardless of their locations, without performing complex surgeries. However, several limitations have been reported, including their side effects, the appearance of primary or secondary resistances, their price and the lack of consensus on treatment regimen and exact duration. The aim of this article was to review the evolution of the management of locally advanced periocular malignant tumours over the last three decades and highlight the new paradigm shift towards the use of ‘eye-sparing’ strategies.

Over the last few years, we have seen constant development of molecular pathology for the care of patients with cancer. The information obtained from molecular data has transformed our thinking about the biological diversity of cancers, particularly in the field of ophthalmic oncology. It has reoriented the way in which therapeutic decisions and decisions concerning patient surveillance are made, both in the area of pediatric cancers, including rhabdomyosarcoma and retinoblastoma, and adult cancers, such as uveal melanoma and lymphomas. A better definition of the molecular classification of these cancers and of the different biological pathways involved is essential to the understanding of both the pathologist and the onco-ophthalmologist. Molecular tests based on targeted or expanded analysis of gene panels are now available. These tests can be performed with tumor tissue or biofluids (especially blood) to predict the prognosis of tumors and, above all, the benefit of targeted therapies, immunotherapy or even chemotherapy. Looking for the BAP1 mutation in uveal melanoma is essential because of the associated metastatic risk. When treating retinoblastoma, it is mandatory to assess the heritable status of RB1. Conjunctival melanoma requires investigation into the BRAF mutation in the case of a locally advanced tumor. The understanding of genomic alterations, the results of molecular tests and/or other biological tests predictive of a therapeutic response, but also of the limits of these tests with respect to the available biological resources, represents a major challenge for optimal patient management in ophthalmic oncology. In this review, we present the current state of knowledge concerning the different molecular alterations and therapeutic targets of interest in ophthalmic oncology.

International audience; This review provides an overview of the applications of α-halogenoacetamides in domino and cycloaddition reactions. α-Halogenoacetamides are versatile building blocks that can lead to a wide variety of complex aza-heterocycles of biological interest when engaged in domino and/or cycloaddition reactions. The reactivity and the reaction conditions involved for these species (solvent, base, etc.) are closely related to the substituent onto the nitrogen atom of the amide: N-alkyl α-halogenoacetamides usually act as formal 1,3-dipoles in domino processes whereas N-alkoxy derivatives often react as real 1,3-dipoles via the formation of aza-oxyallyl cation species. This important modulation of the reactivity of these compounds opens the way to a large panel of reactions and therefore to a large diversity of aza-heterocycles.

Introduction L’association ipilimumab (IPI) + nivolumab (NIVO) offre un taux de réponse et de guérison supérieur aux anti-PD1 en monothérapie mais expose à des événements indésirables immunitaires (EII) plus fréquents. La COVID-19 a tué plus de 3 M de personnes. Comme les patients atteints de cancers sont particulièrement exposés aux formes sévères/mortelles, la vaccination est recommandée. Il n’existe pas de données testant la relation entre vaccination et développement/exacerbation des EII au cours du traitement par ICI. Nous rapportons un cas de myopathie nécrosante survenue 10 jours après la vaccination contre la COVID-19 chez un patient atteint d’un mélanome avancé traité par IPI + NIVO. Matériel et méthodes Un homme de 43 ans était inclus en 2015 dans l’essai adjuvant EORTC MK-3475 (pembrolizumab vs. placebo) pour un mélanome stade IIIb. E n 02/2021 une récidive ganglionnaire lombo-aortique, non opérable survenait. Malgré un statut BRAF (+) et une levée d’aveugle révélant qu’il avait reçu le pembrolizumab (sans EII à l’époque), un traitement par IPI + NIVO était alors débuté. Il recevait sa 1ère et 2e injection les 25/02 et 19/03/21. Le 12/03, il recevait sa 1ère dose de vaccin COVID-19 (Pfizer/BioNTech), sans réaction immédiate. Le 22/03 il développait un tableau associant: myalgies, faiblesse musculaire des membres, dysphagie, dyspnée, dysphonie et diplopie bilatérale avec rhabdomyolyse (CK 12647 U/L). Le bilan immunologique revenait négatif. L’ENMG décrivait un syndrome myogène. L’IRM musculaire révélait un aspect de myosite (muscles rotateurs du cou/de la cuisse) et l’histologie retrouvait un aspect de myopathie inflammatoire avec nécrose multifocale de myocytes et infiltrat inflammatoire à prédominance macrophagique. Le diagnostic de myopathie nécrosante grade IV était retenu. L’immunothérapie était arrêtée et une corticothérapie (bolus puis per os) permettait une amélioration progressive. Le patient est toujours sous corticothérapie orale, la surveillance oncologique montre à ce jour une réponse partielle. La 2e injection du vaccin n’a pas été faite d’autant plus que les IgG étaient fortement positives. Discussion Des myosites secondaires aux ICI, au COVID-19 et de façon plus anecdotique à la vaccination ont été rapportées. Ici, l’association temporelle étroite de la bi-ICI et du diagnostic de myopathie suggère que la myopathie est un EII et que la vaccination a contribué au développement de la myopathie par un effet de boost immunitaire. Le scénario inverse ne peut être exclu. Parce que de plus en plus de patients traités par ICI seront vaccinés dans les prochains mois, les cliniciens doivent être conscients de cette association potentielle du vaccin COVID-19 et de l’exacerbation des EII. Des données prospectives de pharmacovigilance sont nécessaires.

To assess the annual incidence, surgical technique preferred (i.e. external versus endonasal) and the characteristics of patients undergoing a Dacryocystorhinostomy (DCR) in France over a 10-year-period.A national observational cohort study was conducted in France between January 2010 and December 2019. Data were collected from the national PMSI (Programme de Médicalisation des Sytèmes d'Information) database provided by the CNAM (Caisse Nationale de l'Assurance Maladie). All patients undergoing a DCR were included.Twenty-one thousand one hundred ninety-nine patients, with a mean age of 70.4 years, were included. A female predominance (78%) was noted. The mean annual number of DCRs was 2481 (2366-2633), corresponding to a mean incidence of 3.8 per 100,000 person-years. This number remained stable over the study period (The mean annual incidence of external and endonasal DCRs remained stable over the study period. Endonasal DCR was more likely performed by the otorhinolaryngologists, emphasizing the need to develop personalized endonasal training in the ophthalmology residency program.

AimPhantom eye syndrome is a poorly understood and underestimated complication of eye removal (ER). Seeing with the amputated eye, referred to as phantom vision (PV), is undoubtedly the most intriguing and confusing complication experienced by anophthalmic patients. The aim of the study was to assess PV prevalence, clinical features and risk factors after ER.MethodsA multicentric questionnaire-based study was conducted between April 2016 and July 2017. Patients >18 years who underwent ER >3 months ago had a socket examination before inclusion. Data recorded included patients’ demographics, and preoperative, surgical and postoperative features.ResultsOne hundred patients (53 men) with a mean age of 65.1 years (29–92; SD=13.0) were included. ER indications were: uveal melanoma (n=24, 24%), trauma (n=20, 20%), retinal detachment (n=20, 20%), glaucoma (n=14, 14%) and endophthalmitis (n=12, 12%). Thirty (30%) patients experienced PV. Elementary and complex visual hallucinations were experienced by 80% and 20% of patients, respectively. PV usually appeared within the first postoperative month and tended to decrease over time. Risk factors for PV were the preoperative use of proton beam therapy (p=0.006), uveal melanoma (p=0.014), enucleation (p=0.015), anxiety with a Hospital and Anxiety Depression (HAD) score ≥8 (p=0.042), depression with a HAD score ≥8 (p=0.030), phantom eye pain (p=0.044) and phantom eye sensations (p=0.002).ConclusionPV was reported by one-third of our patients. Despite being widely misunderstood, ophthalmologists and neurologists should be aware of this complication to adequately reassure patients.

International audience; Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics

International audience; No abstract available

The purpose of this study is to report our experience with the use of artificial dermis grafts for orbital socket reconstruction following orbital exenteration (OE). A retrospective study was conducted in our ocular oncology centre from May 2018 to June 2020 in patients undergoing OE for orbital malignancies in whom an artificial dermis device (Integra® template, 2 layers) was used for reconstruction. Data recorded included demographics, previous and adjuvant treatments, aetiologies, surgical procedure, surgical reconstruction, complications and follow-up. The main outcome measure was the time between OE and the full granulation of the cavity. Ten patients (mean age, 71.3 years [43–92]) were included. Tumours originated from the conjunctiva (n = 5, 50%), eyelid (n = 3, 30%) and orbit (n = 2, 20%). Nine patients underwent total OE, and one required enlarged OE. Orbital reconstruction was performed using an artificial dermis alone (n = 9, 90%) or combined with regional flaps (n = 1, 10%). The mean granulation time was 3.3 weeks (2–4). Three (30%) patients received adjuvant radiotherapy 1 month post-surgery. The mean time to spontaneous epithelialization was 9.4 weeks (6–12). Preoperative and postoperative radiotherapy was not associated with a delayed epithelialization of the socket (p = 0.463 and p = 0.236, respectively). One (10%) and 2 (20%) patients experienced postoperative socket infection and an ethmoidal fistula, respectively. The mean follow-up was 11.6 months (6–16). Using artificial dermis grafts alone or with regional flaps appears to be a viable surgical procedure for orbital socket reconstruction. They reduce surgical morbidity and hospital stay. Preoperative and postoperative radiotherapy does not seem to delay socket healing.

International audience; An efficient two-step strategy for the synthesis of constrained C-glycosyl amino acid derivatives from C-vinylglycosides involving a 1,3-dipolar cycloaddition using L-(-)menthone-derived nitrone as the key step is described. After optimization of 1,3-dipolar cycloaddition conditions, various C-vinylglycosides were tested leading exclusively to one dia-[a]

PURPOSE Phantom eye syndrome (PES) is an underestimated complication of eye amputation (EA) characterized by phantom eye pain (PEP), phantom visions and/or phantom sensations. The aim of this study was to assess PEP prevalence, features, risk factors, social and psychological consequences and associated quality of life. METHODS A questionnaire study was conducted in three oculoplastic departments between April 2016 and July 2017. Patients >18 years who had undergone EA ≥3 months earlier were included and asked to complete a prestamped questionnaire. Patient's characteristics, preoperative, surgical and postoperative data were collected. RESULTS Of the 185 questionnaires given, 115 (62%) were returned for analysis. Hundred patients with a mean age of 65.1 years (29-92; SD = 13.0) were included. Eye amputation (EA) indications were uveal melanoma (n = 24, 24%), trauma (n = 20, 20%), retinal detachment (n = 20, 20%), glaucoma (n = 14, 14%) and endophthalmitis (n = 12, 12%). Forty-seven (47%), 30 (30%) and 38 (38%) patients experienced PEP, phantom visions and phantom sensations, respectively. Anxiety and depression [Hospital Anxiety Depression scale (HADS) score ≥8 for both] were diagnosed in 34 (34%) and 42 (42%) patients, respectively. The mean EQ-5D-3L and EQ-5D visual analogue scale scores were 0.8 (0.06-1; SD = 0.2) and 68 (0-100; SD = 22), respectively. Preoperative eye pain (p = 0.031), glaucoma (p = 0.027), postoperative anxiety with HADS score ≥8 (p = 0.012) and ≥11 (p = 0.014), aesthetic discomfort (p = 0.002) and EQ-5D-3L score

Intratumor heterogeneity has been recognized in numerous cancers as a major source of metastatic dissemination. In uveal melanomas, the existence and identity of specific subpopulations, their biological function and their contribution to metastasis remain unknown. Here, in multiscale analyses using single-cell RNA sequencing of six different primary uveal melanomas, we uncover an intratumoral heterogeneity at the genomic and transcriptomic level. We identify distinct transcriptional cell states and diverse tumor-associated populations in a subset of the samples. We also decipher a gene regulatory network underlying an invasive and poor prognosis state driven in part by the transcription factor HES6. HES6 heterogenous expression has been validated by RNAscope assays within primary human uveal melanomas, which further unveils the existence of these cells conveying a dismal prognosis in tumors diagnosed with a favorable outcome using bulk analyses. Depletion of HES6 impairs proliferation, migration and metastatic dissemination in vitro and in vivo using the chick chorioallantoic membrane assay, demonstrating the essential role of HES6 in uveal melanomas. Thus, single-cell analysis offers an unprecedented view of primary uveal melanoma heterogeneity, identifies bona fide biomarkers for metastatic cells in the primary tumor, and reveals targetable modules driving growth and metastasis formation. Significantly, our findings demonstrate that HES6 is a valid target to stop uveal melanoma progression.