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Alexandre Matet,1,2 Nawel Amar,1,2 Saddek Mohand-Said,1–4 José-Alain Sahel,1–7 Pierre-Olivier Barale1,2 1INSERM and DHOS, CHNO des Quinze-Vingts, 2Sorbonne Universités, UPMC Univ Paris 6, Institut de la Vision, 3INSERM, 4CNRS, Paris, France; 5Institute of Ophthalmology, University College London, London, UK; 6Fondation Ophtalmologique Adolphe de Rothschild, 7Académie des Sciences, Institut de France, Paris, France Introduction: The Argus II retinal prosthesis is composed of an epiretinal electrode array positioned over the macula and connected to an extrascleral electronics case via a silicone cable, running through a sclerotomy. During implantation, the manufacturer recommends to cover the sclerotomy site with a patch of processed human pericardium to prevent postoperative hypotony and conjunctival erosion by the underlying electronics case. Due to biomedical regulations prohibiting the use of this material in France, we developed an alternative technique combining a scleral flap protecting the sclerotomy and an autogenous graft of superior temporalis fascia overlying the electronics case. Methods: The purpose of this study is to describe the 4-year outcomes of this modified procedure in three subjects who underwent Argus II Retinal Prosthesis System implantation. Clinical data consisting of intraocular pressure measurements and tolerance in terms of conjunctival erosion or inflammation were retrospectively assessed over a 4-year postoperative follow-up. Results: None of the three patients implanted with the modified technique developed ocular hypotony over 4 years. A normal, transient conjunctival inflammation occurred during the first postoperative month but conjunctival erosion was not observed in any of the three patients over 4 years. Four years after implantation, the autogenous temporalis fascia graft remained well tolerated and the retinal prosthesis was functional in all three patients. Conclusion: The combination of an autograft of superficial temporalis fascia and a scleral flap efficiently prevented leakage through the sclerotomy site, ocular hypotony, and conjunctival erosion by the extrascleral electronics case. This modified technique is suitable for the implantation of existing and forthcoming retinal prostheses. Superficial temporalis fascia may also be used as alternative to commercial tectonic tissues for scleral wound repair in clinical settings where they are not available. Keywords: visual prosthesis, retinitis pigmentosa, surgical procedure, conjunctiva, intraocular pressure

Abstract Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology.

Purpose: To investigate the association between the 2 acute phase proteins, C-reactive protein (CRP) and pentraxin 3 (PTX3) with central serous chorioretinopathy (CSCR), as PTX3 is a glucocorticoid-induced protein. Design: Cross-sectional multicenter study. Participants: Patients with CSCR compared with age- and sex-matched healthy participants. Methods: Patients with CSCR from 3 centers in Europe were included in the study. The clinical form of CSCR was recorded. Blood samples from patients with CSCR and healthy participants were sampled, and high-sensitivity CRP and PTX3 levels were measured in the serum. Main Outcome Measures: C-reactive protein and PTX3 serum level comparison between patients with CSCR with age- and sex-matched healthy participants. Results: Although CRP levels were higher in patients with CSCR (n = 216) than in age- and sex-matched controls (n = 130) (2.2 ± 3.2 mg/l vs. 1.5 mg/l ± 1.4, respectively, P = 0.037), PTX3 levels were lower in patients with CSCR (10.5 ± 19.9 pg/ml vs. 87.4 ± 73.2 pg/ml, respectively, P < 0.001). There was no significant difference in CRP or PTX3 levels between patients with acute/recurrent and chronic CSCR. Conclusions: In patients with CSCR, high CRP and low PTX3 levels suggest a form of low-grade systemic inflammation together with a lack of glucocorticoid pathway activation, raising new hypotheses on the pathophysiology of CSCR. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Given a scale (in the sense of Shelah's pcf theory), we list various conditions ensuring that a given point is good for the scale. [ABSTRACT FROM AUTHOR]

Although combined PD-1/CTLA-4 inhibition showed limited efficacy in single-arm, phase II trials in metastatic uveal melanoma (mUM), such combination appears frequently used in mUM patients. We here report our experience with nivolumab/ipilimumab in mUM. A retrospective cohort of 47 mUM patients, 24 men and 23 women, received nivolumab/ipilimumab between October 2019 and December 2021, mostly first line (94%). Two regimens were used: nivolumab 1 mg/kg + ipilimumab 3 mg/kg (nivo1ipi3, 49% of patients) and nivolumab 3 mg/kg + ipilimumab 1 mg/kg (nivo3ipi1, 51% of patients). Median follow-up was 37 and 88 weeks in nivo3ipi1 and nivo1ipi3 cohorts, respectively. We observed partial response in two patients (4%) and stable disease in 14 patients (30%), with no significant difference between the two regimens. Median progression-free survival was 13.6 weeks and 11.9 weeks in the nivo1ipi3 and nivo3ipi1 cohorts, respectively (p = 0.49). Severe adverse events (grade 3 or 4) were observed in seven patients (15%) among which five treated with nivo1ipi3 (22%) and two treated with nivo3ipi1 (8%). These data suggest that nivolumab/ipilimumab combination does not improve clinical outcomes compared to other therapies but is more toxic. In the absence of controlled clinical trials, we would not recommend this combination as a standard treatment in all mUM patients but rather as an option. Patients for whom the benefit–risk ratio could justify the combination need to be defined.

Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology. [ABSTRACT FROM AUTHOR]

Cataract and uveitis are rare in newborns but potentially blinding. Three newborns with cataract and severe anterior uveitis underwent cataract surgery. Spiroplasma ixodetis was detected in lens aspirates using bacterial 16S-rRNA PCR and transmission electron microscopy. These findings, which suggest maternal–fetal infection, are consistent with previous experimental Spiroplasma-induced cataract and uveitis.

Spiroplasma is a genus of Mollicutes, a class of bacteria without cell wall. Spiroplasma are intracellular organisms with helical morphology and a small genome (0.78-2.2 Mb) comprising 38 species isolated [...]

Background Monoallelic germline MBD4 pathogenic variants were recently reported to cause a predisposition to uveal melanoma, associated with a specific tumor mutational signature and good response to immunotherapy. Monoallelic tumor pathogenic variants have also been described in brain tumors, breast cancers, and myxofibrosarcomas, whereas biallelic germline MBD4 pathogenic variants have been involved in a recessive hereditary adenomatous polyposis and a specific type of acute myeloid leukemia. Methods We analyzed MBD4 for all patients with a diagnosis of uveal melanoma at Institut Curie since July 2021 and in the 3240 consecutive female probands explored at the Institut Curie for suspicion of predisposition to breast cancer between July 2021 and February 2023. Results We describe 25 families whose probands carry a monoallelic germline pathogenic variant in MBD4. Eighteen of these families presented with uveal melanoma (including a case patient with multiple uveal melanoma), and 7 families presented with breast cancer. Family histories showed the first familial case of uveal melanoma in monoallelic MBD4 pathogenic variant carriers and other various types of cancers in relatives, especially breast, renal, and colorectal tumors. Conclusions Monoallelic MBD4 pathogenic variant may explain some cases of familial and multiple uveal melanoma as well as various cancer types, expanding the tumor spectrum of this predisposition. Further genetic testing in relatives combined with molecular tumor analyses will help define the tumor spectrum and estimate each tumor's risk. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association between hyperreflective dots (HRD) in the choroid and visual acuity and swept-source optical coherence tomography (SS-OCT)-derived structural parameters in central serous chorioretinopathy (CSC). Methods: SS-OCT images (single visit) of consecutive patients with CSC were evaluated for the presence of HRDs in the choroid using an automated algorithm and manual measurements of central macular and subfoveal choroidal thicknesses were obtained. Results: 61 eyes of 61 subjects were included in this retrospective study (32 subjects with acute and 29 with chronic CSC). Mean (± SD) choroidal HRD counts in acute and chronic CSC were 139.4 ± 29.9 and 124.9 ± 28.1, respectively (P = 0.04). In acute CSC, HRD was correlated with both age (P = 0.004) and subfoveal choroidal thickness (SFCT) (P = 0.016), but not with visual acuity or other OCT-derived measurements. In chronic CSC, HRD was correlated with central macular thickness (P = 0.011); neurosensory detachment height (P = 0.046); SFCT (P = 0.012). Considering all patients, the presence of HRDS was significantly negatively correlated with age (r = -0.401; P= 0.002) and SFCT (r = -0.332; P= 0.010). Conclusion: HRDs are correlated with both age and SFCT in acute CSC, and with CMT, height of neurosensory detachment and SFCT in chronic CSC. Development of HRDS is associated with the remodelling of chorioretinal structures as previously noted in CSC.

PurposeObjective structured clinical examinations (OSCE) evaluate clinical reasoning, communication skills, and interpersonal behavior during medical education. In France, clinical training has long relied on bedside clinical practice in academic hospitals. The need for a simulated teaching environment has recently emerged, due to the increasing number of students admitted to medical schools, and the necessity of objectively evaluating practical skills. This study aimed at investigating the relationships between OSCE grades and current evaluation modalities.MethodsThree-hundred seventy-nine 4th-year students of University-of-Paris Medical School participated to the first large-scale OSCE at this institution, consisting in three OSCE stations (OSCE#1-3). OSCE#1 and #2 focused on cardiovascular clinical skills and competence, whereas OSCE#3 focused on relational skills while providing explanations before planned cholecystectomy. We investigated correlations of OSCE grades with multiple choice (MCQ)-based written examinations and evaluations of clinical skills and behavior (during hospital traineeships); OSCE grade distribution; and the impact of integrating OSCE grades into the current evaluation in terms of student ranking.ResultsThe competence-oriented OSCE#1 and OSCE#2 grades correlated only with MCQ grades (r = 0.19, P0.75). Conversely, the behavior-oriented OSCE#3 grades correlated with traineeship skill and behavior grades (r = 0.19, PConclusionThis large-scale French experience showed that OSCE designed to assess a combination of clinical competence and behavioral skills, increases the discriminatory capacity of current evaluations modalities in French medical schools.