Publications by authors named "Bahram Bodaghi"

209 Publications

Behçet syndrome.

Nat Rev Dis Primers 2021 09 16;7(1):67. Epub 2021 Sep 16.

(Rheumatology) Academic Hospital Istanbul, Istanbul, Turkey.

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life.
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http://dx.doi.org/10.1038/s41572-021-00301-1DOI Listing
September 2021

Immunomodulatory treatment and surgical management of idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children: a French survey practice.

Pediatr Rheumatol Online J 2021 Sep 3;19(1):139. Epub 2021 Sep 3.

Pediatric diseases and Rheumatology, CHU Bordeaux, Bordeaux, France.

Background: Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up.

Methods: We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected.

Results: A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections.

Conclusions: The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.
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http://dx.doi.org/10.1186/s12969-021-00626-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414774PMC
September 2021

Epstein-Barr virus induced post-transplant lymphoproliferative disorder presenting with unilateral retinal involvement.

Am J Ophthalmol Case Rep 2021 Sep 2;23:101186. Epub 2021 Aug 2.

Department of Ophthalmology, Reference Center in Rare Diseases, Pitié Salpêtrière University Hospital, Sorbonne Université, Paris, France.

Purpose: Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of disorders associated with Epstein Barr Virus infection in up to 80% of cases in the setting of pharmacologic immunosuppression following hematopoietic stem cell or solid organ transplantation. Ocular involvement is a rare finding in PTLD.

Observation: We report the case of a 38-year-old man who presented with unilateral retinal infiltrates as first manifestation of PTLD relapse. Diagnosis relied on the presence of EBV DNA in anterior chamber fluids and vitrectomy that showed the presence of a B cell clone. Systemic relapse of PTLD was detected 12 weeks after retinal findings. Treatment of ocular disease included systemic injections of rituximab and intravitreal injections of methotrexate, halting the extension of retinal infiltrates.

Conclusion: Ocular involvement in PTLD is rare and needs to be acknowledged because it can precede a systemic relapse of the hematological condition.
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http://dx.doi.org/10.1016/j.ajoc.2021.101186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361285PMC
September 2021

Perspectives for immunotherapy in noninfectious immune mediated uveitis.

Expert Rev Clin Immunol 2021 Sep 26;17(9):977-989. Epub 2021 Jul 26.

Department of Ophthalmology, DHU ViewRestore, Sorbonne Université, Paris, France.

: Noninfectious uveitis (NIU) is one of the leading causes of blindness worldwide. In adult patients, anterior NIU is usually managed with topical corticosteroids. In intermediate, posterior uveitis. and panuveitis, systemic corticosteroids are used especially in case of bilaterality or association with systemic disease. Biotherapies are recommended in case of inefficacy or intolerance to corticosteroids or conventional immunosuppressive drugs. Anti-TNF-α agents are by far the most widely used biotherapies. In case of failure or poor tolerance to anti-TNF-α, new targeted therapies can be proposed.: We present and discuss an updated overview on biologics and biotherapies in NIU.: In case of dependency to systemic or intravitreal steroids, sight-threatening disease, and/or failure of conventional immunosuppressive drugs, anti-TNF-α are used as first-line biologics to achieve quiescence of inflammation. Anti-interleukin-6 is another option that may be proposed as first-line biologic or in case of poor efficacy of anti-TNF-α. Interferon can be directly proposed in specific indications (e.g. refractory macular edema, sight-threatening Behçet's uveitis). In the rare cases that remain unresponsive to traditional biotherapies, novel molecules, such as Janus-associated-kinase and anti-phosphodiesterase-4-inhibitors can be used. Therapeutic response must always be evaluated by clinical and appropriate ancillary investigations.
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http://dx.doi.org/10.1080/1744666X.2021.1956313DOI Listing
September 2021

A Recurrent Central Band Keratopathy in a Child.

J Rheumatol 2021 Jul 1;48(7):1104-1105. Epub 2021 Jun 1.

DHU Vision et Handicap, Hôpital Universitaire de la Pitié Salpétrière, Département d'Ophtalmologie, Université Pierre and Marie Curie, Sorbonne Universités, Paris, France.

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http://dx.doi.org/10.3899/jrheum.200462DOI Listing
July 2021

Old and New Challenges in Uveitis Associated with Behçet's Disease.

J Clin Med 2021 May 26;10(11). Epub 2021 May 26.

Department of Ophthalmology, IHU FOReSIGHT, Sorbonne-AP-HP, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.

Behçet's disease (BD) is a systemic vasculitis disease of unknown origin occurring in young people, which can be venous, arterial or both, classically occlusive. Ocular involvement is particularly frequent and severe; vascular occlusion secondary to retinal vasculitis may lead to rapid and severe loss of vision. Biologics have transformed the management of intraocular inflammation. However, the diagnosis of BD is still a major challenge. In the absence of a reliable biological marker, diagnosis is based on clinical diagnostic criteria and may be delayed after the appearance of the onset sign. However, therapeutic management of BD needs to be introduced early in order to control inflammation, to preserve visual function and to limit irreversible structural damage. The aim of this review is to provide current data on how innovations in clinical evaluation, investigations and treatments were able to improve the prognosis of uveitis associated with BD.
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http://dx.doi.org/10.3390/jcm10112318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198480PMC
May 2021

Differential Diagnosis of Vitritis in Adult Patients.

Ocul Immunol Inflamm 2021 May 18;29(4):786-795. Epub 2021 May 18.

Department of Ophthalmology, Reference Center in Rare Diseases, DHU Sight Restore, Hôpital Pitié Salpêtrière, Sorbonne Université, Paris, France.

The term "vitritis" refers to the presence of a cellular infiltration of the vitreous body, usually in the context of an intraocular inflammation, but not exclusively. Intermediate uveitis is the most prominent cause of vitritis, including infectious and auto-immune/auto-inflammatory etiologies. Corticosteroids and immunosuppressive therapies should not be started before ruling out the infectious causes of vitritis, especially in immunosuppressed individuals. Other situations can mimic intermediate uveitis such as amyloidosis and ocular tumors. Primary intraocular lymphoma should always be suspected in case of vitreous infiltrations in individuals aged over 50 years.
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http://dx.doi.org/10.1080/09273948.2021.1898001DOI Listing
May 2021

Clinical Characteristics and Outcomes of Eyes with Intraocular Inflammation after Brolucizumab: Post Hoc Analysis of HAWK and HARRIER.

Ophthalmol Retina 2021 May 8. Epub 2021 May 8.

Department of Ophthalmology, Sorbonne University, APHP, Paris, France.

Purpose: This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials.

Design: Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER.

Participants: Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis.

Methods: Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures.

Main Outcome Measures: Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE.

Results: Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0-29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were -0.84 ± 20.6 , -16.31 ± 17.6, and -0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and -7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of -10.4 ± 25.5 ETDRS letters from baseline to EOS.

Conclusions: Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.
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http://dx.doi.org/10.1016/j.oret.2021.05.003DOI Listing
May 2021

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

Am J Hematol 2021 07 3;96(7):823-833. Epub 2021 May 3.

Ophthalmology, Centre Hospitalier Universitaire de Brest, Brest, France.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.
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http://dx.doi.org/10.1002/ajh.26199DOI Listing
July 2021

Classification Criteria for Syphilitic Uveitis.

Am J Ophthalmol 2021 May 11;228:182-191. Epub 2021 May 11.

Department of Medicine, Texas A&M University, College Station, Texas, USA.

Purpose: To determine classification criteria for syphilitic uveitis.

Design: Machine learning of cases with syphilitic uveitis and 24 other uveitides.

Methods: Cases of anterior, intermediate, posterior, and panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the different uveitic classes. The resulting criteria were evaluated on the validation set.

Results: Two hundred twenty-two cases of syphilitic uveitis were evaluated by machine learning, with cases evaluated against other uveitides in the relevant uveitic class. Key criteria for syphilitic uveitis included a compatible uveitic presentation (anterior uveitis; intermediate uveitis; or posterior or panuveitis with retinal, retinal pigment epithelial, or retinal vascular inflammation) and evidence of syphilis infection with a positive treponemal test. The Centers for Disease Control and Prevention reverse screening algorithm for syphilis testing is recommended. The misclassification rates for syphilitic uveitis in the training sets were as follows: anterior uveitides 0%, intermediate uveitides 6.0%, posterior uveitides 0%, panuveitides 0%, and infectious posterior/panuveitides 8.6%. The overall accuracy of the diagnosis of syphilitic uveitis in the validation set was 100% (99% confidence interval 99.5, 100)-that is, the validation set's misclassification rates were 0% for each uveitic class.

Conclusions: The criteria for syphilitic uveitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.
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http://dx.doi.org/10.1016/j.ajo.2021.03.039DOI Listing
May 2021

Catastrophic antiphospholipid syndrome and posterior ocular involvement: case series of 11 patients and literature review.

Retina 2021 Apr 2. Epub 2021 Apr 2.

AP-HP, Cochin Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Université Paris-Descartes, Paris, France. AP-HP, Cochin Hospital, Ophthalmology Department, Paris, France. Centre Hospitalier Saint Joseph Saint Luc, Internal medicine department, Lyon, France. Foch Hospital, Internal Medicine department, Suresnes, France. AP-HP, Henri Mondor Hospital, Internal Medicine department, Creteil, France. AP-HP, La Pitié-Salpêtrière Hospital, Internal Medicine department, Centre de référence maladies auto-immunes et systémiques rares de l'Ile de France, Paris, France. Normandie Université, UNIROUEN, Inserm U1096, Rouen university hospital, department of internal medicine, vascular and thrombosis unit, 76000 Rouen, France. Univ. Lille ; INSERM U1167 ; CHU Lille, Internal Medicine department, Centre National de Référence Maladies Systémiques et Auto-Immunes Rares, European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases (ReCONNECT), F-59000 Lille, France Department of Internal Medicine, CHU de Saint-Etienne, France. Université Paris Descartes-Sorbonne Paris Cité, Paris, France ; INSERM U 1153, Center for Epidemiology and Statistics, Sorbonne Paris Cité (CRESS), Paris, France.

Purpose: To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome (CAPS).

Methods: Retrospective case series of patients presenting with CAPS and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at CAPS diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best corrected visual acuity (BCVA).

Results: This study included 23 patients (11 cases treated by the authors and 12 published case reports), 21 (91%) of them female. Their median age at diagnosis was 28 years (range 16-79). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n=11, 48%), and/or retinal vasculitis (n = 1, 4%). Final BCVA was not significantly worse than BCVA at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months [2-132], nearly half the patients (n = 11, 48%) had permanent vision loss including BCVA < 20/400 for 4 patients.

Conclusion: Posterior ophthalmic manifestations of CAPS were mainly bilateral retinal vascular occlusion, which had the worst visual prognosis, followed by choroidopathy and retinal vasculitis. Permanent visual loss was common.
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http://dx.doi.org/10.1097/IAE.0000000000003185DOI Listing
April 2021

French recommendations for the management of Behçet's disease.

Orphanet J Rare Dis 2021 02 24;16(Suppl 1):352. Epub 2021 Feb 24.

UPMC Université Paris 06, Inserm UMR S 959, Immunology Immunopathology Immunotherapy (I3), Sorbonne Universités, 75005, Paris, France.

Behçet's disease (BD) is a systemic variable vessel vasculitis that involves the skin, mucosa, joints, eyes, arteries, veins, nervous system and gastrointestinal system, presenting with remissions and exacerbations. It is a multifactorial disease, and several triggering factors including oral cavity infections and viruses may induce inflammatory attacks in genetically susceptible individuals. BD vasculitis involves different vessel types and sizes of the vascular tree with mixed-cellular perivascular infiltrates and is often complicated by recurrent thrombosis, particularly in the venous compartment. Several new therapeutic modalities with different mechanisms of action have been studied in patients with BD. A substantial amount of new data have been published on the management of BD, especially with biologics, over the last years. These important therapeutic advances in BD have led us to propose French recommendations for the management of Behçet's disease [Protocole National de Diagnostic et de Soins de la maladie de Behçet (PNDS)]. These recommendations are divided into two parts: (1) the diagnostic process and initial assessment; (2) the therapeutic management. Thirty key points summarize the essence of the recommendations. We highlighted the main differential diagnosis of BD according to the type of clinical involvement; the role of genetics is also discussed, and we indicate the clinical presentations that must lead to the search for a genetic cause.
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http://dx.doi.org/10.1186/s13023-020-01620-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903591PMC
February 2021

Review of the Current Literature and Our Experience on the Value of OCT-angiography in White Dot Syndromes.

Ocul Immunol Inflamm 2021 Feb 22:1-15. Epub 2021 Feb 22.

DHU Sight Restore, Centre Hospitalier National Des Quinze-Vingts, Paris, France.

Purpose: To describe the application of OCT-A in various posterior uveitis disorders in our experience and to compare it with the available literature.

Methods: Eighteen eyes with the diagnoses of multifocal choroiditis (MFC), multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), tuberculous serpiginous-like choroiditis (SLC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSCR) were studied.

Results: We found flow void of the choriocapillaris in patients with APMPPE, SC, MFC, BSCR, and in SLC. In contrast, perfusion of the choriocapillaris seemed normal in patients with MEWDS.

Conclusions: We confirmed that OCT-A contributes new information on the physiopathology of white dot syndromes and inflammatory chorioretinopathies, notably on whether or not the choriocapillaris is involved. Comparing the OCT-A features allowed us to suggest that both APMPPE and SLC might be part of the same spectrum of inflammatory disease with primary involvement at the level of the choriocapillaris and secondary RPE damage.
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http://dx.doi.org/10.1080/09273948.2020.1837185DOI Listing
February 2021

Preventing relapse in non-infectious uveitis affecting the posterior segment of the eye - evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant (ILUVIEN).

J Ophthalmic Inflamm Infect 2020 Nov 30;10(1):32. Epub 2020 Nov 30.

Moorfields Eye Hospital, London, UK.

Background: The current article is a short review of an Alimera Sciences-sponsored symposium held during The 15th International Ocular Inflammation Society Congress in Taiwan on the 14th November 2019 entitled, 'Preventing relapse of non-infectious uveitis effecting the posterior segment of the eye - evaluating the 0.2 μg/day fluocinolone acetonide intravitreal implant.'

Main Text: The fluocinolone acetonide intravitreal implant was approved in Europe for the prevention of relapse in recurrent non-infectious uveitis affecting the posterior segment of the eye and offers a systemic therapy-sparing treatment option by providing low daily dose of corticosteroid into the vitreous for up to 3 years. In the symposium, the presenters reported clinical outcomes from patients with non-infectious uveitis effecting the posterior segment of the eye to support the effectiveness and safety of the implant for up to 3 years in both randomised controlled trials and real-world practices.

Conclusions: Data showed that over a 36 month period, treatment with the fluocinolone acetonide intravitreal implant was associated with significantly fewer episodes of uveitic recurrence, a significantly longer time to uveitic recurrence, greater improvement in visual acuity, a lower need for adjunctive therapy, and an acceptable safety profile.
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http://dx.doi.org/10.1186/s12348-020-00225-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701203PMC
November 2020

Association of Anterior Uveitis With Acute Zika Virus Infection in Adults.

JAMA Ophthalmol 2021 01;139(1):95-102

Department of Ophthalmology, Centre Hospitalier Universitaire, Guadeloupe, French West Indies.

Importance: Acute anterior uveitis has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies based on systemic clinical signs of ZIKV and positive serologic tests.

Objective: To describe the ophthalmic findings associated with systemic ZIKV infection during the 2016 ZIKV outbreak in Guadeloupe in the French West Indies.

Design, Setting, And Participants: This cohort study assessed adult patients with red eye and virologic or serologic confirmation of acute ZIKV infection who were admitted to the Pointe-à-Pitre University Hospital from January 1, 2016, to January 1, 2017, for a systematic ophthalmologic examination. All patients with anterior uveitis also underwent a complete uveitis workup to rule out other causes of uveitis. Patients were excluded from the study if they had active uveitis and a history of uveitis or positive serology for other infectious diseases including dengue fever virus and chikungunya virus. Data were analyzed from January 1, 2016, to January 1, 2017.

Exposures: Patients with confirmed ZIKV infection underwent full ophthalmic examination at study inception and 3, 6, and 12 months.

Main Outcomes And Measures: Description of the presenting ocular characteristics, management, and outcome.

Results: Of 62 total patients with a red eye, 32 (51.6%) had no uveitis (mean [SD] age, 27.8 [3.7] years; 26 women [81.3%]) and 30 (48.4%) had anterior uveitis (mean [SD] age, 27.5 [3.8] years; 26 women [86.7%]), which was bilateral in all cases. Acute anterior uveitis was nongranulomatous and without synechiae, exhibiting mild anterior chamber reaction with small keratic precipitates. Ocular hypertension occurred in 25 patients (83.3%) with uveitis at presentation and persisted in 15 patients (50%) at 1 year despite antiglaucoma therapy and control of uveitis. Uveitis responded to topical steroids in all cases. Intraocular pressure was within normal limits for all patients without uveitis throughout the follow-up period.

Conclusions And Relevance: Anterior uveitis was present in almost half of patients with a red eye and acute systemic ZIKV infection; the uveitis was usually bilateral and often associated with increased intraocular pressure. These results suggest that ophthalmic evaluation should be performed in patients with red eye and acute ZIKV infection to potentially detect and manage hypertensive anterior uveitis.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.5131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689574PMC
January 2021

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis.

Ocul Immunol Inflamm 2020 Nov 17:1-11. Epub 2020 Nov 17.

Northwestern University, Feinberg School of Medicine, Department of Ophthalmology, Chicago, Illinois, USA.

Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Multicentre retrospective analysis. A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.
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http://dx.doi.org/10.1080/09273948.2020.1808226DOI Listing
November 2020

Eplerenone for chronic central serous chorioretinopathy.

Lancet 2020 11;396(10262):1556-1557

Département d'Ophtlalmologie, Centre Hospitalier Universitaire Piite Salpétrière, Paris 75013, France.

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http://dx.doi.org/10.1016/S0140-6736(20)32327-8DOI Listing
November 2020

Biotherapies in Uveitis.

J Clin Med 2020 Nov 8;9(11). Epub 2020 Nov 8.

Department of Internal Medicine and Clinical Immunology, AP-HP, Centre national de références Maladies Autoimmunes et systémiques rares et Maladies Autoinflammatoires rares, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.

Non-infectious uveitis (NIU) represents one of the leading causes of blindness in developed countries. The therapeutic strategy aims to rapidly control intra-ocular inflammation, prevent irremediable ocular damage, allow corticosteroid sparing and save the vision, and has evolved over the last few years. Anterior NIU is mostly managed with topical treatment in adults. However, for intermediate, posterior and pan-uveitis, notably when both eyes are involved, systemic treatment is usually warranted. Biotherapies are recommended in case of inefficacy or non-tolerance of conventional immunosuppressive drugs in non-anterior NIU. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are by far the most widely used, especially adalimumab (ADA) and infliximab (IFX). In case of sight-threatening uveitis in Behçet's disease or in case of risk of severe recurrences, respectively IFX and ADA may be recommended as first-line therapy. Many questions are left unanswered; how long to treat NIU, how to discontinue anti-TNF-α agents, what biologic to use in case of anti-TNF-α failure? The objective of this review is to present an updated overview of knowledge on the use of biological treatments in NIU.
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http://dx.doi.org/10.3390/jcm9113599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695328PMC
November 2020

Prognosis Factors and Outcomes of Neuro-ophthalmologic Sarcoidosis.

Ocul Immunol Inflamm 2020 Nov 9:1-8. Epub 2020 Nov 9.

Département de Médecine Interne et Immunologie Clinique, Sorbonne Université, Centre National De Référence Maladies Autoimmunes Systémiques Rares, Centre National De Référence Maladies Autoinflammatoires et Amylose Inflammatoire. INSERM UMRS 959, Immunologie-Immunopathologie-Immunotherapie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.

: Neuro-ophthalmologic manifestations are uncommon in sarcoidosis. We aim to assess the prognostic factors and outcome of neuro-ophthalmic sarcoidosis.: We conducted a multicenter retrospective study on patients with neuro-ophthalmic sarcoidosis. Response to therapy was based on visual acuity, visual field, and orbital MRI exam. Factors associated with remission and relapse were analyzed.: Thirty-five patients [median (IQR) age of 37 years (26.5-53), 63% of women] were included. The diagnosis of sarcoidosis was concomitant of neuro-ophthalmologic symptoms in 63% of cases. Optic neuritis was the most common manifestation. All patients received corticosteroids and 34% had immunosuppressants. At 6 months, 61% improved, 30% were stable, and 9% worsened. Twenty percent of patients had severe visual deficiency at the end of follow-up. Nonresponders patients had significantly worse visual acuity at baseline ( = 0.01). Relapses were less frequent in patients with retro-bulbar optic neuropathy ( = 0.03).: Prognosis of neuro-ophthalmic sarcoidosis is poor.
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http://dx.doi.org/10.1080/09273948.2020.1834585DOI Listing
November 2020

Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment.

Ophthalmol Retina 2021 06 29;5(6):519-527. Epub 2020 Sep 29.

York Teaching Hospital NHS Foundation Trust, University of York, York, United Kingdom.

Purpose: Recent reports have described a spectrum of uncommon findings of intraocular inflammation (IOI), retinal vasculitis, or retinal vascular occlusion in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. We present guidance on the clinical presentation of this spectrum and propose recommendations for management of these events.

Design: PubMed literature review and expert opinion panel.

Participants: A working group of international medical experts and Novartis medical personnel.

Methods: The working group deliberated on the clinical presentations and used a 3-pronged approach to develop management recommendations based on (1) critical appraisal of scientific literature; (2) clinical insights from the HAWK and HARRIER trials, postmarketing reports, and assessments from an independent Safety Review Committee (SRC); and (3) their clinical experience.

Main Outcome Measures: Management recommendations for a spectrum of ocular inflammatory events after treatment with brolucizumab or other anti-vascular endothelial growth factors (VEGFs).

Results: Based on insights gained from the available information and the expertise of the contributors, recommendations were proposed for ocular examinations, imaging modalities, and treatment strategies for management of this spectrum of events. Patients should be educated to promptly report any relevant or persistent symptoms after IVI to facilitate timely intervention. Patients diagnosed with IOI should be evaluated for concomitant retinal vasculitis or retinal vascular occlusive events. Clinical examination can be augmented with multimodal imaging techniques, including widefield imaging, fluorescein angiography (with peripheral sweeps), and OCT. Once confirmed, the ongoing brolucizumab treatment should be suspended and intensive treatment with potent corticosteroids (topical, subtenon, intravitreal, or systemic) is recommended, which may be supplemented with other treatment strategies depending on the severity. Based on the clinical outcome of these events, individualized treatment with locally available standard of care should be considered for the underlying nAMD.

Conclusions: These recommendations emphasize the need for early diagnosis, prompt and timely intervention, intensive treatment, and frequent monitoring to minimize the risk of progression of these events. The proposed recommendations may facilitate a consistent management approach of this spectrum of ocular inflammatory events should they arise in nAMD after treatment with brolucizumab or other anti-VEGFs.
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http://dx.doi.org/10.1016/j.oret.2020.09.020DOI Listing
June 2021

Recommendations for the management of ocular sarcoidosis from the International Workshop on Ocular Sarcoidosis.

Br J Ophthalmol 2020 Sep 15. Epub 2020 Sep 15.

Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Aims: To establish expert recommendations for the management of ocular sarcoidosis (OS).

Methods: A question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement.

Results: A total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed.

Conclusions: Recommendations for management of OS were formulated through an IWOS consensus workshop.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317354DOI Listing
September 2020

Laser Flare Photometry: A Useful Tool for Monitoring Patients with Juvenile Idiopathic Arthritis-associated Uveitis.

Ocul Immunol Inflamm 2020 Aug 24:1-11. Epub 2020 Aug 24.

Department of Ophthalmology, La Pitié-Salpétrière Hospital, DHU View Restore, Paris, France.

Purpose: We evaluated laser flare photometry (LFP) values in patients with juvenile idiopathic arthritis (JIA)-associated uveitis.

Methods: Retrospective study. A decrease of the LFP value between baseline visit and 1 month after anti-inflammatory treatment intensification allowed us to define two groups of patients: group 1 (decreased LFP value ≥50%) and group 2 (<50%). We evaluated the prevalence of vision-threatening complications in both groups.

Results: Fifty-four patients (87 eyes) were followed for 9.9 ± 5 years. Group 1 eyes (n = 54) had significantly fewer ocular complications than group 2 eyes (n = 33) at both 5 years visit ( = .03) and final visit ( = .047). At the final visit, group 2 eyes had significantly more band keratopathy, trabeculectomy, cataract surgery, glaucoma and papille edema. Group 1 eyes kept a better visual acuity ( < .0001).

Conclusion: The decrease of LFP values ≥50% of the initial value 1 month after treatment intensification is a good early prognostic factor.
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http://dx.doi.org/10.1080/09273948.2020.1792511DOI Listing
August 2020

Drug-induced uveitis: A review.

Indian J Ophthalmol 2020 Sep;68(9):1799-1807

Department of Ophthalmology, IHU FOReSIGHT, Pitie-Salpetriere Universtiy Hospital, Paris, France.

Uveitis maybe induced by the use of various medications known as drug-induced uveitis (DIU), though rare it is an important cause of uveitis which one needs to be aware of. The drugs may be administered through any route including systemic, topical, and intravitreal. Ocular inflammation can be in the form of anterior, intermediate, posterior or pan uveitis, and rarely may present as episcleritis and scleritis. Identification of drug as the offending agent of uveitis is important as many a times stopping the drug may help recover the uveitis or the concomitant use of corticosteroids. An extensive literature review was done using the Pubmed. An overview of DIU is provided as it is important for us to be aware of this clinical entity.
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http://dx.doi.org/10.4103/ijo.IJO_816_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690475PMC
September 2020

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Descriptive Review of Tubercular Uveitis in Paediatric Population.

Ocul Immunol Inflamm 2020 Aug 17:1-7. Epub 2020 Aug 17.

Centre for Ophthalmic Specialised Care, University of Lausanne, Lausanne, Switzerland.

Purpose: To examine disease profile of tubercular uveitis (TBU) in Paediatric population.

Methods: Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed.

Results: Mean age of disease presentation was 12.8 (range 4-18 years), with predominance of males (n = 14/20; 70.0%) and Asian ethnicity (n = 25/29; 86.2%). Posterior uveitis (n = 14/28; 50%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7% (n = 11/17). Incidence of optic disc edema and macular edema was higher in children (n = 8/18; 44.4% and n = 5/18; 27.8%, respectively) than in adults (n = 160/942; 16.9% and n = 135/942; 14.3%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8% (n = 1/21).

Conclusions: Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome.
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http://dx.doi.org/10.1080/09273948.2020.1781197DOI Listing
August 2020

Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France.

Emerg Infect Dis 2020 08;26(8):1792-1800

Linezolid is one of the most effective drugs for treating multidrug-resistant tuberculosis (MDR TB), but adverse effects remain problematic. We evaluated 57 MDR TB patients who had received >1 dose of linezolid during 2011-2016. Overall, patients received 600 mg/day of linezolid for a median of 13 months. In 33 (58%) patients, neurologic or ophthalmologic signs developed, and 18 (32%) had confirmed peripheral neuropathy, which for 78% was irreversible at 12 months after the end of TB treatment despite linezolid withdrawal. Among the 19 patients who underwent ophthalmologic evaluation, 14 patients had optic neuropathy that fully reversed for 2. A total of 16 (33%) of 49 patients had a linezolid trough concentration >2 mg/L, and among these, 14 (88%) experienced adverse effects. No significant association was found between trough concentration and neurologic toxicity. These findings suggest the need to closely monitor patients for neurologic signs and discuss optimal duration of linezolid treatment.
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http://dx.doi.org/10.3201/eid2608.191499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392460PMC
August 2020

Quality of Evidence in Ophthalmology: An Overview of Cochrane Reviews.

Ophthalmology 2021 02 9;128(2):330-332. Epub 2020 Jul 9.

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département Santé Publique, Institut hospitalo-universitaire FOReSIGHT, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.ophtha.2020.07.003DOI Listing
February 2021

Child-Adult Transition in Sarcoidosis: A Series of 52 Patients.

J Clin Med 2020 Jul 3;9(7). Epub 2020 Jul 3.

AP-HP Pediatric Pulmonology Department and Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, 75012 Paris, France.

(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (≤15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (±2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3-44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0-32), resulting in mostly mild (18; 35.3%) and rarely severe (2; 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood.
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http://dx.doi.org/10.3390/jcm9072097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408766PMC
July 2020

UVEITIS TREATED WITH DEXAMETHASONE IMPLANT.

Retina 2021 Mar;41(3):620-629

Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Université Lyon 1, Lyon, France.

Purpose: To evaluate the real-life efficacy and safety of the intravitreal dexamethasone implant in uveitis.

Methods: This retrospective observational multicentric study included 152 eyes treated exclusively by 358 dexamethasone implant injections. The main outcome measures included change in the best-corrected visual acuity, central macular thickness, and vitreous haze score.

Results: Patients were treated with dexamethasone implant for macular edema (51.3%), vitritis with macular edema (40.1%), vitritis (5.3%), and other causes (3.3%). The mean duration of follow-up was 19.0 months. The mean gain in best-corrected visual acuity during follow-up was +12.1 letters. An improvement in best-corrected visual acuity ≥5, 10, and 15 letters was found in 64.5, 50.7, and 35.5% of cases, respectively. 59.7% of eyes with macular edema at baseline were found to be anatomical responders. Vitritis resolution (vitreous haze = 0+) was obtained in 81.4% of cases. Ocular hypertension (intraocular pressure ≥25 mmHg and/or gain ≥10 mmHg from baseline) occurred in 28.3% of patients. No filtering surgery/laser therapy was required. A total of 40.2% of phakic subjects underwent cataract surgery on average 11.2 months after the first injection.

Conclusion: This study confirms the efficacy and safety of the dexamethasone implant in noninfectious uveitis. Cataract and ocular hypertension were not uncommon but easily manageable.
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http://dx.doi.org/10.1097/IAE.0000000000002901DOI Listing
March 2021

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak.

Expert Rev Clin Immunol 2020 07 21;16(7):651-657. Epub 2020 Jul 21.

Department of Ophthalmology, IHU FOReSIGHT, Sorbonne University-APHP , Paris, France.

Introduction: Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression.

Areas Covered: This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic.

Expert Opinion: Management should proceed as usual when access to health care possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection, and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.
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http://dx.doi.org/10.1080/1744666X.2020.1791086DOI Listing
July 2020

Ethnic differences in normal retinal capillary density and foveal avascular zone measurements.

Int Ophthalmol 2020 Nov 29;40(11):3043-3048. Epub 2020 Jun 29.

Ophthalmology Department, Avicenne Hospital, 125 rue de Stalingrad, 93000, Bobigny, France.

Background: The purpose of this study was to quantify retinal capillary density and foveal avascular zone (FAZ) area in healthy subjects according to their ethnicity, using optical coherence tomography angiography (OCTA).

Methods: In this cross-sectional study, all eyes underwent swept-source OCTA (Triton, Topcon, Tokyo, Japan). Macular OCTA scans (3 × 3 mm) were obtained in healthy white Caucasian and black African subjects. The FAZ area and capillary density in both the superficial (SCP) and deep capillary plexuses (DCP) were automatically measured using a custom-made software combining vessel binarization and skeletonization.

Results: Twelve eyes of 12 healthy Caucasians and 15 eyes of 15 healthy black Africans were included in the analysis. The mean FAZ area was significantly smaller, and the overall vessel density (VD) was higher in the SCP and DCP of Caucasians compared to black Africans. The mean FAZ area was 0.26 ± 0.008 mm in the SCP and 0.25 ± 0.05 mm in the DCP in Caucasians versus 0.33 ± 0.08 mm in the SCP (p = 0.01) and 0.37 ± 0.1 mm in the DCP (p = 0.03) in Africans. In the SCP and DCP, the mean VD was, respectively, 40.5 ± 0.8% and 47.1 ± 0.5% in Caucasians versus 34.3 ± 1% (p = 0.008) and 40.6 ± 0.9% in Africans (p < 0.001).

Discussion/conclusion: In the SCP and DCP, VD is lower in black Africans compared to Caucasians. In OCTA studies on vascular diseases, ethnicity-matched measurements from healthy subjects should be used for comparisons.
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http://dx.doi.org/10.1007/s10792-020-01488-0DOI Listing
November 2020
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