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Abstract Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide. To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

ABSTRACT: Mechanical and physicochemical treatments of milk induce structural modifications of the casein (CN) micelles, affecting their techno-functional properties in dairy processing. Here, we studied the effect of alkalinization and ultra-high-pressure homogenization (UHPH) on CN micelles in raw skim milk (rSM) and pasteurized skim milk (pSM). The pH of both skim milks (approximately 6.7) was adjusted to 8.5 and 10.5 before UHPH at 100, 200, and 300 MPa. The structural changes of the CN micelles during the treatments were assessed using laser diffraction, transmission electron microscopy, and turbidity measurements. Finally, ultracentrifugation (70,000 × g for 1 h at 20°C) was carried out to evaluate the protein's distribution between the supernatant (serum phase) and the pellet (colloidal phase) by gel electrophoresis and protein concentration measurement. Alkalinization of both skim milks induced a significant reduction in turbidity, whereas an increase of the average particle size was observed, the effect being more severe in pSM than rSM. At alkaline pH, more proteins were recovered in the serum phase, which suggested that the CN underwent major rearrangements into nonsedimentable CN forms of various sizes, as confirmed by transmission electron microscopy. The amount of CN found in the serum phase at pH 8.5 also increased with the UHPH pressure. Although UHPH did not influence the average CN micelle size at pH 6.7 and 8.5, a pressure-dependent decrease was observed at pH 10.5 for both skim milks. The structural changes of the CN micelles observed in this study throughout the combination of alkalinization and UHPH could be of interest for developing new dairy ingredients with improved functionality.

Aims: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis., Methods: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation., Results: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively., Conclusion: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile., Competing Interests: Competing interests: Bahram Bodaghi: Alimera, Abbvie, Optos, Zeiss, Thea, Horus, Active biotech. Laurent Kodjikian: Alimera, Abbvie, Novartis, Bayer, Roche, Horus, Krys. Sara Touhami: Allergen, Novartis, Horus, Bayer pharma. Pascal Sève: Abbvie, Pfizer, Sanofi, Lilly, GSK, UCB Pharma., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background/objectives: The predictive factors of surgical results in uveitic retinal detachment (RD) are lacking. The objective was to study the surgical outcomes and determine the risk factors for surgical failure in rhegmatogenous RD associated with intraocular inflammation (RRDIOI)., Methods: Retrospective series of consecutive eyes with RRDIOI undergoing vitreoretinal surgery between 2012 and 2019 in two French referral centres. Patients underwent 23- or 25 G pars plana vitrectomy (PPV), scleral buckling (SB), or a combination of both. The main objective was to describe the predictive factors of visual recovery and anatomical success after surgery., Results: Seventy-one eyes were included. Posterior and panuveitis accounted for 91.5% of eyes. Seventy-five percent of eyes had an infectious cause for their uveitis. The first surgery consisted in PPV alone, SB alone, or both in 87.3%, 4.2% and 8.5% of cases respectively. The reattachment rate was 74.6% after one surgery (100% in case of SB, either alone or in association with PPV). On multivariate analysis, the only predictive factor of visual improvement was a baseline BCVA ≥ 20/400, while the only predictive factor for surgical success at 12 months was the absence of RD recurrence within the first 6 weeks of surgery., Conclusions: RRDIOI has a relatively favourable anatomical prognosis. The addition of scleral buckling may be beneficial in selected cases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Viruses belonging to the herpes family group, including HSV (herpes simplex virus) 1 and 2, VZV (varicella zoster virus) and CMV (cytomegalovirus) are the leading causes of necrotizing retinitis. These viral retinal necroses generally manifest in three forms, depending on the patient's immune status: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN) and CMV retinitis. Although specific, effective drug treatments are available today, early treatment initiation is essential to avoid sight-threatening complications., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: To describe a case of CBL syndrome presenting with life-threatening pediatric Epstein-Barr virus (EBV) infection and sight-threatening rod-cone dystrophy (RCD) masquerading as severe panuveitis., Methods: Single case report with results of whole-exome sequencing (WES) analysis in the proband and his parents. Data were collected from July 2009 to December 2022., Results: A 35-month-old boy presented with severe primary EBV infection complicated by encephalitis and hemophagocytic lymphohistiocytosis. The clinical picture abated with systemic corticosteroids. Genetic testing revealed a heterozygous germline pathogenic variant in the CBL gene c.1141T > G (p.Cys381Gly). At 6 years old, he developed a severe bilateral panuveitis requiring multiple lines of immunosuppressants, mostly to control refractory cystoid macular edema (CME). During follow-up, intraretinal pigment deposits and peripheral retinal atrophy started to appear. Full-field electroretinogram (ffERG) revealed a pattern consistent with RCD. Repeat WES targeting known inherited retinal disease (IRD) genes was negative. A diagnosis of CBL syndrome complicated by RCD masquerading as severe bilateral panuveitis was made, and CME treatment was switched to oral acetazolamide., Conclusions: CBL syndrome can present with severe EBV infection early in life. RCD masquerading as severe panuveitis is also a possible feature of CBL syndrome. RCD should be kept in mind in patients with this syndrome who present with idiopathic intraocular inflammation and are refractory to IMT. Carbonic anhydrase inhibitors (CAI) should be tried early to treat CME., 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: We investigated the anatomical and functional results of vitrectomy associated with the peeling of secondary epiretinal membranes (ERM) in patients with retinal vein occlusion (RVO) and determined the prognostic factors of surgical outcomes., Methods: This retrospective, multicenter, observational study included 50 patients with RVO who underwent vitrectomy with ERM removal between July 2012 and February 2021. Visual acuity (VA) and central macular thickness (CMT) were investigated up to 3 years. Univariate analysis identified the predictive factors associated with functional and anatomical outcomes., Results: Fifty eyes from 50 patients (62% with central RVO) were included. The mean VA of 0.9 ± 0.7 logMAR preoperatively improved to 0.5 ± 0.5 logMAR after 24 months (p = 0.01). Anatomically, the mean preoperative CMT was 501 ± 168 μm, decreasing to 348 ± 108 μm at month 24 (p = 0.008). By 36 months, VA had improved or stabilized in 90% of the eyes, whereas CMT had been reduced by at least 20% from baseline in 80% of the eyes. A lower number of intravitreal injections (IVI) were required after vitrectomy. Worse preoperative VA, absence of preoperative panretinal photocoagulation, and postoperative use of adjunctive IVI were associated with VA recovery. Higher baseline CMT and the use of preoperative dexamethasone injections were associated with an improvement in CMT., Conclusion: Vitrectomy for ERM secondary to RVO was effective in improving VA and recovering CMT for up to 3 years and reduced the number of IVIs., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Despite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Conflict of Interest: None of the authors has any conflicting interests to disclose.

Purpose: To report the clinical features and treatment outcomes in adult Caucasians with ocular toxocariasis (OT) and investigate their prognosis depending on their serological status., Methods: Retrospective observational cohort study (2016-2021) including consecutive adults with uveitis and positive western blot (WB) in the aqueous humor or vitreous. The presence of serum antibodies was not necessary for inclusion, allowing to compare the outcomes depending on the serological status., Results: Seventeen eyes of 15 patients were included. Mean age at diagnosis was 51.9 years. Vitreous inflammation was the most frequent sign (100%). Vitreoretinal tractions (41.2%) and chorioretinal granulomas (58.8%) were less prevalent. Atypical features were: spontaneous intravitreal hemorrhage (23.5%), exudative retinal detachment (11.8%), isolated macular edema (17.6%), papillitis (29.4%) and vasculitis (47.1%). Twenty percent of patients had a positive serum serology. Baseline clinical features did not differ statistically depending on the serological status; however, the degree of inflammation was numerically higher in patients with negative serology. Overall, macular thickness, anterior and posterior segment inflammation improved significantly after treatment with oral albendazole, systemic ± local corticosteroids. Vitrectomy (47.1%) was performed in case of persistent vitritis (62.5%), retinal detachment (12.5%) and intravitreous hemorrhage (25%)., Conclusion: OT has no pathognomonic sign and atypical presentations were not infrequent in this adult Caucasian cohort. Serum antibodies were rarely positive, stressing on the importance of ocular sample analysis, especially in case of atypical features. Serum antibodies may prove useful in forecasting the rapidity of inflammation clearance. Antiparasitic and anti-inflammatory treatment was safe and efficient in most cases.

Background: Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME., Methods: Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied., Results: 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA., Conclusion: DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To describe a case of T-cell prolymphocytic leukemia (T-PLL) masquerading as viral retinal necrosis (VRN)., Case Presentation: A 75-year-old-man with a history of T-PLL in complete remission complained of an acute vision loss in his right and only eye. Ophthalmic examination demonstrated the presence of anterior chamber cells, mild vitritis, and peripheral retinal whitening with intraretinal hemorrhages evocative of VRN. While the anterior chamber tap came back negative for HSV, VZV, and CMV, cytology performed on the aqueous humor described the presence of leukemic cells., Conclusion: T-PLL can rarely masquerade as a viral retinal necrosis. Diagnostic work-up should therefore always rule out the infectious causes of retinitis. Anterior chamber tap can sometimes prove useful in the diagnosis of T-PLL even in the absence of a hypopyon, avoiding the need for vitrectomy.

Background/purpose: Evaluate the performance of a deep learning algorithm for the automated detection and grading of vitritis on ultrawide-field imaging., Methods: Cross-sectional noninterventional study. Ultrawide-field fundus retinophotographs of uveitis patients were used. Vitreous haze was defined according to the six steps of the Standardization of Uveitis Nomenclature classification. The deep learning framework TensorFlow and the DenseNet121 convolutional neural network were used to perform the classification task. The best fitted model was tested in a validation study., Results: One thousand one hundred eighty-one images were included. The performance of the model for the detection of vitritis was good with a sensitivity of 91%, a specificity of 89%, an accuracy of 0.90, and an area under the receiver operating characteristics curve of 0.97. When used on an external set of images, the accuracy for the detection of vitritis was 0.78. The accuracy to classify vitritis in one of the six Standardization of Uveitis Nomenclature grades was limited (0.61) but improved to 0.75 when the grades were grouped into three categories. When accepting an error of one grade, the accuracy for the six-class classification increased to 0.90, suggesting the need for a larger sample to improve the model performances., Conclusion: A new deep learning model based on ultrawide-field fundus imaging that produces an efficient tool for the detection of vitritis was described. The performance of the model for the grading into three categories of increasing vitritis severity was acceptable. The performance for the six-class grading of vitritis was limited but can probably be improved with a larger set of images.

Purpose: To report a case of Fibroblast Growth Factor Receptor inhibitor (FGFRi) associated retinopathy in a patient treated with Erdafitinib., Case Report: A patient with a history of non-muscle invasive urothelial carcinoma treated with Erdafitinib developed symptomatic unifocal bilateral serous retinal detachments (SRD) eight weeks after starting this new treatment. Six months after discontinuing the drug, the SRDs resolved and visual acuity recovered to baseline. However, hyper and hypo auto fluorescent lesions were still visible on fundus autofluorescence, suggesting a still ongoing retinal pigment epithelium (RPE) impairment., Conclusions: Cancer treatments using FGFRi are showing promising results but their ocular toxicity is not well reported nor fully understood. Oncologists should be aware of the potential risks associated with FGFRi and involve ophthalmologists for the follow-up of their patients. The toxicity of FGFRi seems to resolve after drug continuation, but a certain degree of infra clinical RPE impairment may persist. Longer term follow-ups are warranted to further understand the effects of FGFRi on the RPE., 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.

Objective: To investigate clinical and spectral-domain optical coherence tomography (SD-OCT) biomarkers correlating with pre-injection visual acuity (VA), post-injection VA, and the likelihood of macular oedema (MO) regression following dexamethasone (DEX) implant injection in non-infectious uveitic (NIU) patients., Methods: Patient data from Uveitis Services in Milan, Paris, and Berlin were analysed. Eligible participants were NIU patients aged >18 years with MO as the primary indication for DEX treatment. SD-OCT scans and clinical data were collected at the time of DEX injection (pre-injection visit) and after 3 months (post-injection visit). Multivariable regression models, adjusted for pre-injection VA and lens status, were employed to explore associations. MO regression was defined as the absence of intraretinal/subretinal fluid at the post-injection visit., Results: Our analysis comprised data from 173 DEX treatments, encompassing 103 eyes from 80 patients, with 38 eyes (37%) receiving repeated DEX injections. The absence of the ellipsoid zone (EZ) layer and disorganisation of the inner retinal layers (DRIL) were associated with worse pre- (+0.19 LogMAR, 95% CI 0.01-0.38, p = 0.06, and +0.10 LogMAR, 95% CI 0.02-0.21, p = 0.01) and post-injection VA (+0.33 LogMAR, 95% CI 0.08-0.57, p = 0.01, and +0.17 LogMAR, 95% CI 0.01-0.32, p = 0.04). EZ disruption and DRIL increased significantly (p = 0.01 and p = 0.04), and the chance of gaining ≥5 letters declined in eyes undergoing repeated DEX (p = 0.002). The rate of MO regression after each DEX was 67%. Prolonged MO duration (OR = 0.75/each year, p = 0.02) was associated with reduced likelihood of MO regression. Subretinal fluid was associated with higher rate of MO regression (OR = 6.09, p = 0.01)., Conclusion: Integrity of the inner and outer retina is associated with better visual response to DEX. Long-standing or recurrent MO is associated with less chance of both visual and anatomic response. Timely treatment is necessary to maximise the outcomes of MO in NIU patients., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien ® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response., Methods: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi)., Results: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 μm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections., Conclusion: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

Design: Case Report Case description: This report describes the case of a female patient diagnosed with oculo-cerebral toxocariasis manifesting initially in the form of isolated bilateral cystoid macular edema. Diagnosis was made by means of positive anterior chamber and lumbar puncture western blots. The unusual presentation, ancillary findings and treatment are discussed. The control of intraocular inflammation that was only partially responsive to steroids was eventually achieved with pegylated interferon alfa-2a., Conclusion: Isolated macular edema is a rare presentation of ocular toxocariasis. Interferon alfa-2a may prove useful in case of insufficient control of inflammation.

Typical retinitis pigmentosa (RP) may not be the only retinal phenotype encountered in ataxia with vitamin E deficiency (AVED). The following short case series describes a novel form of retinopathy in AVED. We describe two patients with AVED belonging to the same consanguineous sibship. Both presented an unusual retinopathy consisting of scattered, multifocal, nummular, hyperautofluorescent atrophic retinal patches. The retinopathy remained stable under vitamin E supplementation. We hypothesize these changes to be the result of arrested AVED-related RP following early supplementation with α-tocopherol acetate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Ocular sarcoidosis is present in 30-60% of all sarcoidosis patients. Our purpose is to increase awareness of the various presentations of ocular sarcoidosis., Methods: Short image-based clinical case report., Results: We report on a case of ocular sarcoidosis presenting with unilateral choroidal nodules in a middle-aged man. Sarcoid uveitis is generally bilateral and rather symmetrical. However, choroidal nodules are an exception to this rule, as they generally arise unilaterally. Choroidal nodules are highly responsive to oral corticosteroids. When left untreated, they may evolve to chorioretinal atrophy and secondary choroidal neovascularization., Conclusions: Knowledge of this presentation of ocular sarcoidosis can help clinicians optimize treatment outcomes for patients.

Competing Interests: The authors report no conflicts of interest.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Systemic drugs can treat various retinal pathologies such as retinal cancers; however, their ocular diffusion may be limited by the blood-retina barrier (BRB). Sonication corresponds to the use of ultrasound (US) to increase the permeability of cell barriers including in the BRB. The objective was to study the efficacy and safety of sonication using microbubble-assisted low-intensity pulsed US in inducing a transient opening of the BRB. The eyes of C57/BL6J mice were sonicated at different acoustic pressures (0.10 to 0.50 MPa). Efficacy analyses consisted of fluorescein angiography (FA) performed at different timepoints and the size of the leaked molecules was assessed using FITC-marked dextrans. Tolerance was assessed by fundus photographs, optical coherence tomography, immunohistochemistry, RT-qPCR, and electroretinograms. Sonication at 0.15 MPa was the most suitable pressure for transient BRB permeabilization without altering the morphology or function of the retina. It did not increase the expression of inflammation or apoptosis markers in the retina, retinal pigment epithelium, or choroid. The dextran assay suggested that drugs up to 150 kDa in size can cross the BRB. Microbubble-assisted sonication at an optimized acoustic pressure of 0.15 MPa provides a non-invasive method to transiently open the BRB, increasing the retinal diffusion of systemic drugs without inducing any noticeable side-effect.

Aim: To analyse the choroidal thickness (CT) and vessel pattern of myopic patients with dome-shaped macula (DSM) and their association with the DSM axis and serous retinal detachment (SRD)., Methods: Retrospective study. The CT and vessel pattern were assessed on optical coherence tomography (OCT), OCT-angiography and ultra-wide-field photography., Results: 27 eyes of 18 subjects (mean age: 65 years) were included. Compared with the 11 eyes (41%) with horizontal DSM, the 16 eyes (59%) with vertical DSM had a shorter axial length (25.8±2 mm vs 28.3±2.5 mm; p=0.01), a higher mean macular bulge height (624.4±207 µm vs 255.4±160.3 µm; p=0.0001) and a thicker CT (183.1±91.1 µm vs 72±38.3 µm; p<0.001). Large choroidal vessels crossed the macular area in 75% of eyes with vertical DSM vs 27% of eyes with horizontal DSM (p=0.02), whereas a watershed zone framing the macula was more often seen in horizontal DSM (72% vs 25%, p=0.02). Thirteen eyes (48%) had an SRD that was not associated with the DSM axis, the mean bulge height, the CT or the vessel pattern., Conclusion: The presence of an SRD did not correlate with the DSM axis, the CT or the vessel pattern. However, the rate of large choroidal vessels crossing the macula was higher in vertical DSM than in horizontal DSM., Competing Interests: Competing interests: PN, none; AC reports personal fees from Allergan, Bayer and Novartis, outside of the submitted work. DG, none; ST, none; GLG, none; AG, none; RT reports personal fees from Novartis, Bayer, Roche, Genentech, Allergan, Zeiss, Alcon and Oculus, outside of the submitted work; EP reports personal fees from Bayer and Novartis outside of the submitted work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Describe the clinical and virological characteristics of viral necrotizing retinitis (VNR) and assess its prognostic factors. Methods: Retrospective study (Pitié Salpêtrière Hospital, Paris) of consecutive VNR patients diagnosed and monitored by qPCR on aqueous humor between 2015 and 2019. All patients received induction therapy with intravenous +/− intravitreal injections (IVI) of antivirals. Results: Forty-one eyes of 37 patients with a mean age of 56 years were included. Involved viruses were VZV (44%), CMV (37%) and HSV2 (19%). Acute retinal necrosis represented 51%, progressive outer retinal necrosis 12% and CMV retinitis 37% of eyes. Forty-six percent of patients were immunocompromised. Median BCVA was 0.7 LogMAR at baseline and 0.8 LogMAR after an average of 14.1 months. VNR bilateralized in 27% of cases after 32 months. Retinal detachment (RD) occurred in 27% of cases after a mean duration of 98 days. Factors associated with a “poor BCVA” at 1 month were: advanced age, low baseline BCVA, high vitritis grade and viral load (VL) at baseline and the “slow responder” status (i.e., VL decrease <50% after 2 weeks of treatment). Factors associated with RD were: advanced age, immunocompetence, low baseline BCVA, high vitritis grade at baseline and use of ≤5 IVIs. Conclusions: Clinical factors including advanced age, immunocompetence, low BCVA and high vitritis grade at baseline were associated with a poor prognosis. New virological factors were predictive of a poor outcome: high baseline VL and the “slow responder” status. Sequential intraocular fluid sampling might help prognosticate the outcomes of VNR.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi-Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

Purpose: To compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA)., Design: Observational retrospective multicenter study., Methods: A total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti-tumor necrosis factor [TNF]-α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients' medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety., Results: Main etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti-TNF-α agents., Conclusions: In sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME)., Design: Multicenter, retrospective, observational study., Participants: Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both., Methods: Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16])., Main Outcome Measures: Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months., Results: Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients., Conclusions: Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the anatomical and functional outcomes of pars plana vitrectomy (PPV) and epiretinal membrane (ERM) peeling in patients with retinal vein occlusion (RVO) and secondary ERM., Methods: Retrospective, multicenter study including patients with RVO and ERM who underwent PPV and ERM peeling with or without phacoemulsification. Demographic, clinical, surgical, and optical coherence tomography (OCT) features were recorded at the time of ERM peeling (baseline). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were longitudinally collected up to 36 months after surgery. Clinical factors associated with BCVA and CMT and disappearance of macular edema during follow-up were investigated., Results: Twenty-one eyes of 21 patients with a median follow-up of 18 months were included. The BCVA improved significantly after ERM peeling (baseline vs. 24 months, p = 0.01). Absence of the external liming membrane/ellipsoid zone on OCT was associated with worse visual outcomes (regression estimate [95% confidence interval, CI] = 0.93 [0.39-1.48] logMAR, p = 0.004). Eyes with disorganization of the inner retinal layers at baseline had higher CMT values at each visit (regression estimate [95% CI] = 114.1 [78.9-219.4] μm, p = 0.004). Older age at the time of RVO (p = 0.03) and branch RVO (p = 0.04) were risk factors for persistent macular edema after ERM removal., Conclusion: PPV and ERM removal provided encouraging functional and morphological results in eyes with RVO, with disappearance of macular edema in most eyes. The integrity of the outer retina and preservation of inner retinal segmentation were associated with better visual and anatomical outcomes after ERM removal, respectively., (© 2022. The Author(s).)

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM) and the leading cause of blindness in patients with DM. In the pathogenesis of DR, chronic hyperglycemia leads to biochemical and structural alterations in retinal blood vessels' wall, resulting in hyperpermeability and non-perfusion. Since vascular endothelial growth factor (VEGF) has been found to play a significant role in the pathogenesis of DR, this review sheds light on the effect of intravitreal anti-VEGF agents on retinal non-perfusion in patients with DR. Based on the existing literature, anti-VEGF agents have been shown to improve DR severity, although they cannot reverse retinal ischemia. The results of the published studies are controversial and differ based on the location of retinal non-perfusion, as well as the imaging modality used to assess retinal non-perfusion. In cases of macular non-perfusion, most of studies showed no change in both fundus fluorescein angiography (FFA) and optical coherence tomography (OCTA) in patients with DR treated with intravitreal anti-VEGF agents, while few studies reported worsening of non-perfusion with enlargement of foveal avascular zone (FAZ). Regarding peripheral ischemia, studies using wide-field-FFA demonstrated an improvement or stability in non-perfusion areas after anti-VEGF treatment. However, the use of wide-field-OCTA revealed no signs of re-perfusion of retinal vessels post anti-VEGF treatment. Further prospective studies with long follow-up and large sample size are still needed to draw solid conclusions., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Hypoxia is potentially one of the essential triggers in the pathogenesis of wet age-related macular degeneration (wetAMD), characterized by choroidal neovascularization (CNV) which is driven by the accumulation of subretinal mononuclear phagocytes (MP) that include monocyte-derived cells. Here we show that systemic hypoxia (10% O 2 ) increased subretinal MP infiltration and inhibited inflammation resolution after laser-induced subretinal injury in vivo. Accordingly, hypoxic (2% O 2 ) human monocytes (Mo) resisted elimination by RPE cells in co-culture. In Mos from hypoxic mice, Thrombospondin 1 mRNA (Thbs1) was most downregulated compared to normoxic animals and hypoxia repressed Thbs-1 expression in human monocytes in vitro. Hypoxic ambient air inhibited MP clearance during the resolution phase of laser-injury in wildtype animals, but had no effect on the exaggerated subretinal MP infiltration observed in normoxic Thbs1 -/- -mice. Recombinant Thrombospondin 1 protein (TSP-1) completely reversed the pathogenic effect of hypoxia in Thbs1 -/- -mice, and accelerated inflammation resolution and inhibited CNV in wildtype mice. Together, our results demonstrate that systemic hypoxia disturbs TSP-1-dependent subretinal immune suppression and promotes pathogenic subretinal inflammation and can be therapeutically countered by local recombinant TSP-1.