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Abstract Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

The new generation internal beam dump of the Super Proton Synchrotron (SPS) at CERN will have to dissipate approximately 270 kW of thermal power, deposited by the primary proton beam. For this purpose, it is essential that the cooling system features a very efficient heat evacuation. Diffusion bonding assisted by hot isostatic pressing (HIP) was identified as a promising method of joining the cooling circuits and the materials of the dumps core in order to maximize the heat transfer efficiency. This paper presents the investigation of HIP assisted diffusion bonding between two CuCr1Zr blanks enclosing SS 316L tubes and the realization of a real size prototype of one of the dump’s cooling plates, as well as the assessments of its cooling performance under the dump’s most critical operational scenarios. Energy-dispersive x-ray spectroscopy, microstructural analyses, measurements of thermal conductivity, and mechanical strength were performed to characterize the HIP diffusion bonded interfaces (CuCr1Zr-CuCr1Zr and CuCr1Zr-SS 316L). A test bench allowed to assess the cooling performance of the real size prototype. At the bonded interface, the presence of typical diffusional phenomena was observed. Moreover, measured tensile strength and thermal conductivity were at least equivalent to the lowest ones of the materials assembled and comparable to its bulk properties, meaning that a good bonding quality was achieved. Finally, the real size prototype was successfully tested with an ad hoc thermal test bench and with the highest operational thermal power expected in the new generation SPS internal beam dump. These results demonstrated the possibility to use HIP as a manufacturing technique for the cooling plates of the new generation SPS internal beam dump, but they also open up the way for further investigations on its exploitability to improve the cooling performance of any future high intensity beam intercepting device or in general devices requiring very efficient heat evacuation systems.

Background: The visual outcome after central retinal artery occlusion (CRAO) is poor, but its relationship with early reperfusion (ER) is poorly known. We evaluated the incidence of ER in acute CRAO or branch retinal artery occlusion (BRAO), and its association with clinical outcome., Methods: In this prospective observational multicenter study, we included patients with acute CRAO or macula-involving BRAO presenting within 24 hours from symptom onset. ER was evaluated within 24 hours after the initial clinical evaluation using indocyanine green angiography (ICGA). The primary outcome was the best-corrected visual acuity (BCVA) at 1 month., Results: In all, 70 patients were enrolled, of whom 63 (90%) had CRAO. Median age was 71 years (interquartile range: 67-77), 63% were male, median time from symptom onset to presentation was 5.3 hours (interquartile range: 3.1-15.1), and 17% received intravenous fibrinolysis. ER was identified in 34 patients (49%), of whom 21 (30%) achieved complete reperfusion (100% filling of the 55° ICGA field). Patients with ER were less likely to have hypertension and diabetes mellitus ( p  < 0.001 and p  = 0.046, respectively). At the 1-month follow-up, BCVA was significantly better in ER patients (median BCVA 1.3 logMAR vs 1.7 logMAR, p  = 0.001), with greater benefit with complete reperfusion ( p for trend < 0.001). ER was also associated with improved visual field and quality of life at the 1-month follow-up (both p  < 0.05)., Conclusion: ER occurred in almost 50% of the patients and was associated with improved visual outcomes and quality of life. Therapies that increase ER in CRAO will likely improve clinical outcomes., Clinical Trial Registration: This study was registered on ClinicalTrials.gov (identifier NCT03049514 ); https://classic.clinicaltrials.gov/ct2/show/NCT03049514., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Malignant hypertension has not disappeared and remains the most severe form of hypertension. More than 100 years after its description, many points remain unanswered. Mechanisms, definitions, and optimal treatment are still controversial. In 2019, we decided to launch a prospective multicentre multidisciplinary cohort in France to try to fill these gaps., Method: This study aimed to describe the baseline characteristics of the first 302 included patients and compared these data to already published cohorts. We included patients with severe hypertension associated with severe hypertensive retinopathy and patients filling the HYP MOD (HYPertension MultiOrgan Damage) definition from a broad range of departments (cardiology, nephrology, neurology intensive care unit, emergency department, internal medicine). We collected clinical, biological, imaging, and target organ damage data at admission, along with social and demographic data. We also recorded diagnostic and therapeutic management, adverse events during hospitalization, and characteristics at discharge., Results: We enrolled 302 patients in 32 months (105/year) among 40 centres and different specialties. They mainly included young men (68%, mean age 48.7 ± 14.5 years). Target organ damage involved the eye in 86.7% of patients, kidney in 58.6%, heart in 50%, brain in 32.8%, and Thrombotic Microangiopathy stigmata in 15.6%. Patients with severe retinopathy shared characteristics similar to those included in the most important cohorts already published. We also reported several additional subgroups of interest: one-third of our patients were less than 40 years old, one-third were of non-European origin, 14.3% were included through the multiorgan damage definition, without fundus severe injuries, 22.8% were treated without the use of IV therapy, 40.9% had normal or low renin level, and almost all patients were not on antihypertensive therapy at the time of the enrolment., Conclusion: These preliminary findings already challenge long-standing dogma, raise numerous questions, and provide a solid basis to address them in ancillary studies of the cohort., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives : To report ophthalmological and microvascular findings in patients with post-acute COVID-19. Methods : In this prospective, monocentric cohort study, we included patients with post-acute COVID-19 who presented with ophthalmological symptoms. All patients underwent indocyanine green angiography (ICGA), OCT, OCT-angiography, adaptive optics, and GlycoCheck assessments. Results: We included 44 patients, predominantly female (81.8%), with a mean age of 47.5 ± 11.5 years. Key ICGA findings revealed hyperreflective dots in 32 eyes (36.4%) and hemangioma-like lesions in 7 eyes (8.0%). Capillary non-perfusion in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was observed in 42 eyes (47.7%) and 21 eyes (23.9%), respectively. Eyes with hyperreflective dots exhibited a lower perfused boundary region (PBR), while those with superficial punctate keratitis showed a higher PBR ( p = 0.02 and p = 0.002, respectively). Eyes with capillary non-perfusion in the SCP displayed lower capillary densities (CD4, CD5, and CD4-6; p = 0.001, 0.03, and 0.03, respectively), and eyes with non-perfusion in the DCP had lower CD4 ( p = 0.03). A negative correlation was identified between capillary density and the wall-to-lumen ratio. Conclusions: Patients with post-acute COVID-19 demonstrate both retinal and choroidal vascular anomalies. Ocular pathology was associated with reduced capillary density. These injuries appear to stem more from microvascular disruptions than from persistent glycocalyx abnormalities.

Introduction: Small full-thickness macular holes (FTMHs) are classically treated surgically but can also occasionally close spontaneously. Long-term visual outcomes of spontaneously closed FTMHs are not well described. We compared best-corrected visual acuity (BCVA) after surgical and spontaneous closure of idiopathic FTMH (IMHs) and assessed the effect of IMH size on BCVA., Methods: This retrospective study was performed at Rothschild Foundation Hospital, Paris, France, from January 2015 to June 2021. The study included patients with small IMH, i.e., ≤250 μm, divided into spontaneously closed IMH (SIMH) and surgically closed IMH. Both groups were divided into 3 subgroups according to IMH diameter: <100 μm, 100-150 μm, or 151-200 μm., Results: A total of 109 patients had surgical IMH closure and 18 spontaneous IMH closure. Among all the patients of the study, we observed 17% of spontaneous closure. All SIMHs were <250 μm. The groups did not differ in final BCVA or BCVA gain. BCVA significantly improved after surgery whatever the IMH size. In the SIMH group, final BCVA did not differ by IMH size. In the 100-150 μm subgroups, BCVA gain was significantly greater for the surgical closure compared to the SIMH groups (-0.35 ± 0.2 vs. -0.16 ± 0.2 logMAR; p = 0.01)., Conclusion: Vision results are similar between spontaneously closed and surgically closed macular holes. Spontaneous closure of macular holes can occur; it is therefore reasonable to consider observation before macular hole surgery., (© 2024 S. Karger AG, Basel.)

Purpose: To elaborate a deep learning (DL) model for automatic prediction of late recurrence (LR) of rhegmatogenous retinal detachment (RRD) using pseudocolor and fundus autofluorescence (AF) ultra-wide field (UWF) images obtained preoperatively and postoperatively., Materials and Methods: We retrospectively included patients >18 years who underwent either scleral buckling (SB) or pars plana vitrectomy (PPV) for primary or recurrent RRD with a post-operative follow-up >2 years. Records of RRD recurrence between 6 weeks and 2 years after surgery served as a ground truth for the training of the deep learning (DL) models. Four separate DL models were trained to predict LR within the 2 postoperative years (binary outputs) using, respectively, UWF preoperative and postoperative pseudocolor images and UWF preoperative and postoperative AF images., Results: A total of 412 eyes were included in the study (332 eyes treated with PPV and 80 eyes with SB). The mean follow-up was 4.0 ± 2.1 years. The DL models based on preoperative and postoperative pseudocolor UWF imaging predicted recurrence with 85.6% (sensitivity 86.7%, specificity 85.4%) and 90.2% accuracy (sensitivity 87.0%, specificity 90.8%) in PPV-treated eyes, and 87.0% (sensitivity 86.7%, specificity 87.0%) and 91.1% (sensitivity 88.2%, specificity 91.9%) in SB-treated eyes, respectively. The DL models using preoperative and postoperative AF-UWF imaging predicted recurrence with 87.6% (sensitivity 84.0% and specificity 88.3%) and 91.0% (sensitivity 88.9%, specificity 91.5%) accuracy in PPV eyes, and 86.5% (sensitivity 87.5%; specificity 86.2%) and 90.6% (sensitivity 90.0%, specificity 90.7%) in SB eyes, respectively. Among the risk factors detected with visualisation methods, potential novel ones were extensive laser retinopexy and asymmetric staphyloma., Conclusions: DL can accurately predict the LR of RRD based on UWF images (especially postoperative ones), which can help refine follow-up strategies. Saliency maps might provide further insight into the dynamics of RRD recurrence., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Artificial intelligence(AI)-based methods have been extensively used for the detection and management of various common retinal conditions, but their targeted development for inherited retinal diseases (IRD) is still nascent. In the context of limited availability of retinal subspecialists, genetic testing and genetic counseling, there is a high need for accurate and accessible diagnostic methods. The currently available AI studies, aiming for detection, classification, and prediction of IRD, remain mainly retrospective and include relatively limited numbers of patients due to their scarcity. We summarize the latest findings and clinical implications of machine-learning algorithms in IRD, highlighting the achievements and challenges of AI to assist ophthalmologists in their clinical practice., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To assess the long-term efficacy and safety of treatments for cystoid macular edema in birdshot retinochoroïditis., Methods: Observational retrospective study of 142 HLA-A29-positive patients with cystoid macular edema; the main outcome was the optical coherence tomography intraretinal cysts resolution., Results: During the mean follow-up of 75 months (12-178), 61.3% of patients were successfully treated using 1 to 3 treatment steps, while the others needed more steps. At 6 months, there were no significant effects on ME for anti-TNF (tumor necrosis factor) and IVIg (immunoglobulin) in contrast to antimetabolites (OR 1.98), systemic GCS (glucocorticosteroids), CsA (cyclosporine A) and tocilizumab (odds ratio closed to 2.7), intraocular injected GCS (odds ratio of 4.2), and interferon (odds ratio of 4.4). The percentages of therapeutic success trend to decrease from the initial three treatment steps to the subsequent treatment steps, for systemic GCS (84% to 70%), for anti-TNF (42% to 33%), and for CsA (71% to 33%); the success percentages did not decrease for injected GCS (83% to 89%). Macular edema recurrence occurred with the highest percentage for injected GCS (86.8%, P = 0.01) and the lowest for tocilizumab (10.5%, P = 0.001). Interferons-α and tocilizumab were associated with the lowest prednisone daily doses., Conclusion: The classical uveitic cystoid macular edema therapeutic algorithm could be adapted to birdshot retinochoroïditis.

Purpose: To assess the prevalence of fovea plana in patients with rhegmatogenous retinal detachment and compare characteristics of the detachment between patients with and without fovea plana., Methods: This retrospective, cross-sectional, case-control study included individuals with rhegmatogenous retinal detachment. We collected demographics and data on the operated eye, spherical equivalent, best-corrected visual acuity, lens status, macula status, number of retinal holes or tears, and presence of intravitreal hemorrhage, macular hole, epiretinal membrane, posterior vitreous detachment and proliferative vitreoretinopathy. The type of surgery, the tamponade, and cataract surgery following retinal surgery were also recorded. Spectral-domain optical coherence tomography macular cubes were used to evaluate the fovea by using the Spectralis HRA-OCT device (Heidelberg Engineering, Germany). Images were graded by two different investigators and a third investigator in case of disagreement., Results: We included 204 individuals; 35 (17.2%) had fovea plana, a proportion significantly higher than in the general population (p = 0.041). Individuals with and without fovea plana did not differ in any of the characteristics mentioned above apart from posterior vitreous detachment, which was more frequent in those with than without fovea plana (p = 0.038)., Conclusion: The prevalence of fovea plana is higher in patients with rhegmatogenous retinal detachment, which suggests an association between fovea plana and potential vitreoretinal interface changes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Fovea plana is indicative of an immature inner retina, yet its association with epimacular membrane (ERM) remains unexplored. This study aims to investigate the prevalence of fovea plana in the contralateral eye of patients diagnosed with ERM., Methods: A retrospective analysis was conducted on consecutive patients in a monocentric tertiary ophthalmic department between January and April 2021. The study included all patients referred for ERM, with dense optical coherence tomography (OCT) B-scans utilized to assess the incidence of fovea plana in the contralateral eye. Patients with bilateral ERM were excluded from the analysis., Results: Out of 181 patients, 26 exhibited fovea plana in the contralateral eye, resulting in an incidence rate of 14.3%. Demographic characteristics, OCT patterns, and indications for surgery did not differ significantly between patients with and without fovea plana., Discussion: The prevalence of fovea plana in patients with ERM did not exhibit a statistically significant increase compared to the reported incidence in patients undergoing preoperative cataract surgery., Conclusion: In our cohort, the incidence of fovea plana in patients with ERM was determined to be 14.3%., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices., (© 2024. The Author(s).)

Introduction: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care., Patients and Methods: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria., Results: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ., Conclusion: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal., (© 2024. The Author(s).)

Introduction: An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution., Methods and Analysis: A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms., Ethics and Dissemination: The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients., Trial Registration Number: NCT04624737., Competing Interests: Competing interests: RT discloses the following competing interests: AbbVie Allergan (F, C, R), Alcon (F, C), Apellis (C), Bayer (F, C, R), Boehringer Ingelheim (F), Roche-Genentech (C, R), Iveric Bio (C), KHB (C, R), Novartis (F, C, R), Oculis (C, R), Thea (C), Zeiss (F). SB is consultant for AbbVie, Bayer, Oculis, Optic 2000 and Novartis. SM is employed by Zeiss. ALG is employed by Evolucare. AC is consultant for AbbVie, Bayer, Horus, Novartis and Roche. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The incidence of retinal displacement after rhegmatogenous retinal detachment (RRD) surgery is variable and its clinical consequences are unclear. The aim of this study was to assess the incidence and clinical features of retinal displacement after RRD surgery by using ultra-widefield (UWF) imaging., Methods: Retrospective observational study including all consecutive patients who underwent RRD surgery at the Rothschild Foundation Hospital. Postoperative data included the visual acuity and symptoms of visual impairment. Macular retinal displacement occurrence and its features were assessed and measured by using the autofluorescence images., Results: A total of 123 eyes were included. UWF fundus autofluorescence revealed the presence of macular retinal displacement in 14 (11%) eyes. All displacements were inferior, with a mean angle of 3.8°. Patients with and without macular displacement did not differ in postoperative visual acuity. The retinal detachment extent and preoperative macular involvement were not significantly associated with the occurrence of retinal displacement., Conclusion: In this representative cohort of eyes that underwent RRD surgery with systematic screening for postoperative retinal displacement by UWF fundus autofluorescence, 11% of eyes experienced an inferior retinal shift. As in other cohorts, the presence of metamorphopsia was not associated with the occurrence of retinal shift., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To report a case of bilateral paracentral acute middle maculopathy lesions on spectral domain-optical coherence tomography(OCT) secondary to severe Plasmodium falciparum malaria., Methods: Retrospective case report. Spectral domain-OCT, ultra-widefield fluorescein angiography, and OCT angiography were performed and analyzed., Results: A 54-year-old healthy man presented with acute vision loss in both eyes few days after being diagnosed with severe Plasmodium falciparum malaria. Ophthalmoscopic examination was unremarkable, but near-infrared reflectance imaging showed patchy hyporeflective areas located at the terminal tips of the venous branches. Corresponding spectral-domain OCT demonstrated alternating bands of hyperreflectivity involving the inner nuclear layer, consistent with skip paracentral acute middle maculopathy lesions. Optical coherance tomography angiography illustrated corresponding flow signal loss at the level of the deep capillary plexus. Ultra-widefield fluorescein angiography showed peripheral retinal vein staining and capillary nonperfusion., Conclusion: Paracentral acute middle maculopathy may be an OCT manifestation of malarial retinopathy associated with severe Plasmodium falciparum infection.

Optical coherence tomography angiography (OCTA) can deliver enhanced diagnosis for diabetic retinopathy (DR). This study evaluated a deep learning (DL) algorithm for automatic DR severity assessment using high-resolution and ultra-widefield (UWF) OCTA. Diabetic patients were examined with 6×6 mm2 high-resolution OCTA and 15×15 mm2 UWF-OCTA using PLEX®Elite 9000. A novel DL algorithm was trained for automatic DR severity inference using both OCTA acquisitions. The algorithm employed a unique hybrid fusion framework, integrating structural and flow information from both acquisitions. It was trained on data from 875 eyes of 444 patients. Tested on 53 patients (97 eyes), the algorithm achieved a good area under the receiver operating characteristic curve (AUC) for detecting DR (0.8868), moderate non-proliferative DR (0.8276), severe non-proliferative DR (0.8376), and proliferative/treated DR (0.9070). These results significantly outperformed detection with the 6×6 mm2 (AUC = 0.8462, 0.7793, 0.7889, and 0.8104, respectively) or 15×15 mm2 (AUC = 0.8251, 0.7745, 0.7967, and 0.8786, respectively) acquisitions alone. Thus, combining high-resolution and UWF-OCTA acquisitions holds the potential for improved early and late-stage DR detection, offering a foundation for enhancing DR management and a clear path for future works involving expanded datasets and integrating additional imaging modalities.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: To determine the loss of follow-up ratio and reasons during the COVID-19 lockdown in patients with retinal diseases treated by anti-vascular endothelial growth factor intravitreal injections and to report the visual outcome and rate of complications of these patients 1 year after the end of the lockdown., Methods: This is a prospective descriptive cohort study (NCT04395859) conducted at the Rothschild Foundation Hospital - Paris between April 2020 and May 2021. Patients with retinal diseases treated by repeated intravitreal anti-VEGF injections (IVI) since before October 2019 were included. They filled-out a questionnaire and were followed up during a period of 1 year., Results: During the COVID-19 lockdown 198 eyes (82.5%) of 157 patients (82.6%) received their injections in a timely manner (group 1) while 42 eyes (17.5%) of 33 patients (17.4%) had their injections delayed or missed (group 2). No statistically significant difference was found between group 1 and group 2 when comparing the change of mean best corrected distance visual acuity (BCVA) between month 12 and inclusion ( p  = 0.6) and the rate of ocular complications. The most frequent reasons for missing scheduled injections are appointments cancellation by the hospital (12 patients, 36%), fear of virus exposure during transportation (7 patients, 21%) or at the hospital (5 patients, 15%). Eighty-four percent (130/157 patients) of patients who attended their appointment were satisfied by the protective measures used in the hospital., Conclusion: COVID-19 lockdown did not seem to negatively affect the 1-year outcome of patients with retinal diseases treated by anti-VEGF IVIs who missed their scheduled injections. The BCVA and rate of complications at 1 year did not differ whether patients missed their scheduled injections or not. Maintaining IVIs during lockdown periods and educating patients about the risks of missing injections are pivotal in improving prognosis of retinal diseases.

Background: Fovea plana is defined as an immature macula diagnosed by OCT, showing the unusual shunt of the inner retinal layers into the fovea. The incidence of fovea plana in the adult population remains to be determined. The aim of this study was to determine the incidence of fovea plana in the French population with age-related cataract., Methods: Consecutive patients who underwent cataract surgery in Rothschild Foundation Hospital, France, between January and March 2021, with preoperative analyzable OCT scans available, were retrospectively screened in order to determine the incidence of fovea plana in these population. Ophthalmological characteristics of patients were reported, and detailed., Result: Fovea plana was encountered in 20 out of 204 patients during the 3 months corresponding to an incidence of 9.8%. One of those patients had stage 2 fovea plana., Conclusion: Although fovea plana is defined as an immature macula, it is not rare in preoperative population. This macular aspect was not associated with poor visual acuity in our cohort.

Purpose: To assess a new optical coherence tomography angiography (OCTA) technology and its contribution to retinal vascularization and choriocapillaris (CC) exploration., Methods: A new module, named "Beam expander" (BE), which increases the lateral resolution of OCTA, was used in combination with a prototype software in the PLEX® Elite 9000 Swept-Source OCT instrument (ZEISS, Dublin, CA). This prospective study involved 22 healthy subjects imaged with and without BE. Qualitative analysis of superficial capillary plexus (SCP), deep capillary complex (DCC) retinal and CC angiograms were performed. Perfusion density (PD), vessel density (VD), and foveal avascular zone (FAZ) measurements were also compared., Results: Qualitative analysis of single SCP and DCC retinal angiograms acquired with BE showed significantly better vessel sharpness (respectively, p = 0.0002, and p<0.0001), and greater peripheral image quality (p = 0.028 and p = 0.007) compared to standard OCTA images. Mean VD of whole retina single scans was significantly higher for BE angiograms compared to classic angiograms (28.16 ±1.29 mm-1 and 23.36 ±0.92 mm-1, respectively, p<0.0001). Repeatability of VD, PD and FAZ raw size were found to be similar between the two methods (intraclass correlation coefficient: 0.671, 0.604 and 0.994 with BE versus 0.764, 0.638 and 0.990 without BE). CC image quality was found to be significantly superior with BE, and flow deficits were more visible in all BE scans compared to standard scans., Conclusions: An increase in lateral resolution of the OCT beam resulted in higher quality of retinal and choriocapillaris OCTA images in healthy subjects. These results provide significant insights into the future OCTA imaging enhancements., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Warren Lewis and Luis de Sisternes are employeed of Zeiss. Sophie Kubach was employeed of Zeiss. Dr. Négrier, Dr Erginay, Dr Nassisi and Dr Lavia have nothing to disclose. Dr. Bonnin reports personal fees from Allergan, outside the submitted work. Dr. Couturier reports personal fees from Allergan, Bayer and Novartis, outside the submitted work. Prof. Tadayoni reports personal fees from Novartis, Bayer, Roche, Genentech, Allergan, Zeiss, Alcon and Oculis, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Bonnin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To describe central serous chorioretinopathy cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases., Methods: Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging, and biometry of four eyes of three patients were assessed. A literature review was conducted., Results: The three patients had peripheral choroidal detachment and inferior bullous retinal detachment associated with central serous chorioretinopathy features detected using multimodal imaging, including fluorescein and indocyanine green angiography. The choroid was thick in the three patients, and uveal effusion occurred after steroid treatment in all cases. Subretinal fluid drainage and deep sclerectomy with flaps of 4 × 4 mm in both inferior quadrants were performed in three eyes of two patients with good outcomes. One patient was treated with photodynamic therapy. All three patients developed a typical leopard-spot pigmentary pattern in the fundus., Conclusion: A severe presentation of highly exudative central serous chorioretinopathy may occur in rare cases with a peripheral choroidal detachment mimicking uveal effusion syndrome. These severe cases highlighted the role of choroidal thickening and hyperpermeability, choroidal vein dilation, and possible scleral thickening in both entities.

Near-infrared reflectance (NIR) retinal imaging aids in a better visualization of structures at the level of outer retina, retinal pigment epithelium, and choroid. It has multiple advantages, including easy acquisition in association with structural spectral domain optical coherence tomography, more comfort for patients, and enhanced contrast and spatial resolution. It helps in the diagnosis of chorioretinal diseases that present with minimal funduscopic findings and can be used to follow up many chorioretinal conditions. We describe the chorioretinal NIR imaging appearance and the clinical role of NIR imaging in ocular inflammatory disease, vascular and acquired disease, degenerative disease, tumors, associated systemic condition, toxic and traumatic disease, optic nerve head conditions, and physiological findings., Competing Interests: Disclosures The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Malignant hypertension has not disappeared and is associated with a poor prognosis. Yet, so far, it has received limited attention from the medical community. Guidelines are mainly based on expert consensus and low quality evidences., Method: We set up a prospective, multicenter, observational cohort of patients with malignant hypertension. We collect at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients., Discussion: The HAMA (Hypertension Arterielle MAligne, meaning malignant hypertension) registry aims to describe the epidemiology and to assess the prognosis of malignant hypertension in a contemporary multidisciplinary cohort, with emphasis on the diversity of current management and care pathway among the different medical specialties. It may help improving our pathophysiological knowledge, and pave the way to update the definition of this particular form of hypertension. The multidisciplinary network developed in the wake of this project is expected to facilitate the set up therapeutic trials, laying the ground for evidence-based recommendations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Permanent visual impairment is a major complication of giant cell arteritis (GCA). We investigated the added value of color Doppler imaging (CDI) of the central retinal artery (CRA) in patients with suspected GCA for early risk evaluation before temporal artery biopsy (TAB) results become available., Methods: We conducted a non-interventional observational study of 30 consecutive patients hospitalized for suspected GCA, including a comprehensive analysis of clinical, laboratory, imaging, CDI and pathology data. GCA was diagnosed or excluded (GCA+, GCA-, respectively) according to American College of Rheumatology (ACR) criteria and TAB findings. Three patients not meeting ACR criteria were excluded secondarily. The GCA- group contained ten patients, and the GCA+ group contained 17 patients, including eight with unilateral, transient or permanent clinical visual impairment (CVI)., Results: Mean blood flow velocity (mBFV) in the CRA was impaired in the affected eyes of GCA + CVI+ patients (1.9 ± 0.9 cm.s -1 , p < 0.001) relative to controls (4.1 ± 1.0 cm.s -1 ), GCA- patients (3.6 ± 0.7 cm.s -1 ) and GCA + CVI- patients (3.8 ± 0.8 cm.s -1 ). The mBFVs of the CRA was similar for affected and fellow eyes (right or left). CRA mBFV measurements effectively differentiated between patients with and without CVI (ROC-curve analysis, AUC = 0.925 [95%CI: 0.700 to 0.996], p < 0.0001, 88% sensitivity, 89% specificity, and cutoff of ≤2.7 cm.s -1 for affected eyes; 75% sensitivity, 100% specificity and cutoff of ≤2.2 cm.s -1 for fellow eyes)., Conclusion: CDI facilities the early detection of visual ischemia risk in GCA+ patients, justifying urgent high-dose corticosteroid administration to save at least the fellow eye before pathology results become available., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To determine the prevalence and characteristics of foveal hypoplasia (also called fovea plana) in patients with Best disease using spectral-domain (SD) optical coherence tomography (OCT) and OCT-angiography (OCT-A)., Design: A retrospective observational study including patients diagnosed with Best disease., Subjects and Participants: Fifty-nine eyes of thirty-two patients (fifteen females (46.9%) and seventeen males (53.1%), p = 0.9) diagnosed with Best disease were included. Patients' eyes were categorized into two groups: Eyes with a fovea plana appearance ('FP group') and eyes without fovea plana appearance ('no FP group'), based on the foveal appearance on B-scan SD-OCT., Methods and Main Outcome Measures: Cross-sectional OCT images were assessed for the persistence of inner retinal layers (IRL) and OCT-A was analyzed for the presence of a foveal avascular zone (FAZ), the size of which was determined when applicable., Results: Overall, 16 eyes (27.1%) of 9 patients had a fovea plana appearance ('FP group') with the persistence of IRL, and 43 eyes (72.9%) of 23 patients did not have fovea plana appearance ('no FP group'). Among FP eyes, OCT-A performed in 13 eyes showed bridging vessels through the FAZ in 100% of eyes with OCT-A. Using Thomas classification, 14 out of the 16 eyes with fovea plana (87.5%) had atypical foveal hypoplasia, and the 2 others (12.5%) had a grade 1b fovea plana., Conclusion: In our series, foveal hypoplasia was present in 27.1% of patients with Best disease. OCT-A showed bridging vessels through the FAZ in all eyes. These findings highlight the microvascular changes associated with Best disease, which can be an early sign of the disease in patients with a family history.

Objectives: Invasive aspergillosis is a threat for immunocompromised patients. We present a case series of aggressive cerebral vasculitis caused by Aspergillus spp. infection in immunocompromised patients., Methods: We present a retrospective case series of three autopsy-proven invasive cerebral aspergillosis with diffuse vasculitis affecting large caliber cerebral vessels., Results: Three patients were immunosuppressed: one on rituximab, one on corticosteroids, and one with a renal transplant. Two of these patients were diagnosed with cerebral aspergillosis on postmortem., Conclusion: Aspergillus cerebral vasculitis is a rare form of invasive aspergillosis that should be considered in an immunocompromised individual with suggestive lesions on imaging. It should be suspected as a possible cause of aseptic neutrophil meningitis., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ligand-dependent corepressor (LCOR) mediates normal and malignant breast stem cell differentiation. Cancer stem cells (CSCs) generate phenotypic heterogeneity and drive therapy resistance, yet their role in immunotherapy is poorly understood. Here we show that immune-checkpoint blockade (ICB) therapy selects for LCOR low CSCs with reduced antigen processing/presentation machinery (APM) driving immune escape and ICB resistance in triple-negative breast cancer (TNBC). We unveil an unexpected function of LCOR as a master transcriptional activator of APM genes binding to IFN-stimulated response elements (ISREs) in an IFN signaling-independent manner. Through genetic modification of LCOR expression, we demonstrate its central role in modulation of tumor immunogenicity and ICB responsiveness. In TNBC, LCOR associates with ICB clinical response. Importantly, extracellular vesicle (EV) Lcor-messenger RNA therapy in combination with anti-PD-L1 overcame resistance and eradicated breast cancer metastasis in preclinical models. Collectively, these data support LCOR as a promising target for enhancement of ICB efficacy in TNBC, by boosting of tumor APM independently of IFN., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphoma, whereas PARP-1 deficiency accelerates lymphomagenesis in the Eμ-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in preleukemic Eμ-Myc B cells, resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1 deficiency induces a proinflammatory response and an increase in regulatory T cells, likely contributing to immune escape of B-cell lymphoma, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centered therapeutic strategies, with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumors., (© 2022 by The American Society of Hematology.)

Oncogene-induced senescence (OIS) is a form of stable cell-cycle arrest arising in response to oncogenic stimulation. OIS must be bypassed for transformation, but the mechanisms of OIS establishment and bypass remain poorly understood, especially at the post-transcriptional level. Here, we show that the RNA-binding protein UNR/CSDE1 enables OIS in primary mouse keratinocytes. Depletion of CSDE1 leads to senescence bypass, cell immortalization, and tumor formation, indicating that CSDE1 behaves as a tumor suppressor. Unbiased high-throughput analyses uncovered that CSDE1 promotes OIS by two independent molecular mechanisms: enhancement of the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repression of Ybx1 mRNA translation. Importantly, depletion of YBX1 from immortal keratinocytes rescues senescence and uncouples proliferation arrest from the SASP, revealing multilayered mechanisms exerted by CSDE1 to coordinate senescence. Our data highlight the relevance of post-transcriptional control in the regulation of senescence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We report the long-term outcome of uveitis associated with cancer immunotherapy (CIT). Methods:  This retrospective review included serial patients with CIT-associated uveitis treated using various regimen. Results: Eight patients treated with rituximab (anti-CD20), nivolumab (anti-PD-1), ipilimumab (anti-CTLA-4), vemurafenib and dabrafenib (anti-BRAF), trametinib (anti-MEK) and ibritunib showed uveitis with hypopion (one patient), macular edema (five patients) and choroiditis (two patients). Various regimens of corticosteroid therapy showed a favorable ophthalmological outcome, whether the CIT was continuing or suspended. Conclusion: Local corticosteroid injections in combination with CIT could be suggested as a first-line treatment. This could help to preserve the quality of life without threatening the vital prognosis.

Purpose: The purpose of this paper was to present our study on the relationship between the parafoveal sensitivity measured using microperimetry and the vessel density (VD) assessed by optical coherence tomography-angiography (OCT-A) in eyes with diabetic retinopathy (DR)., Methods: The observational case series was conducted in a tertiary ophthalmology center. Eyes with DR and without macular edema were consecutively included. All eyes underwent microperimetry and OCT-A. The correlation between the regional retinal sensitivity and the corresponding local capillary changes and structural alterations seen on OCT-A was assessed in each retinal quadrant., Results: Thirty-seven eyes of 21 patients were included. The mean retinal sensitivity was 28.7 ± 2 decibel (dB). The mean parafoveal VD was 43.2 ± 4.2% in the superficial capillary plexus (SCP) and 48.1 ± 3.3% in the deep capillary complex (DCC). In the multivariate linear regression model, the mean retinal sensitivity was positively correlated with the VD in the SCP in the parafoveal ring (P = 0.01) and with the inner nuclear layer (INL) thickness (P = 0.01). The qualitative analysis of each quadrant showed the presence of areas of capillary dropout with a normal sensitivity. Conversely, all areas of decreased sensitivity (<25 dB) were associated with a decreased VD in the SCP and the DCC., Conclusions: The parafoveal sensitivity positively correlated with the VD in the SCP in DR eyes. Areas with a low retinal sensitivity were always co-located with a loss of capillaries in the SCP and the DCC despite preserved outer retinal layers.