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Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 32875

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Prof. Dr. Pascal Sève

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Internal Medicine, University of Lyon, Lyon, France
Interests: uveitis; sarcoidosis
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Intraocular inflammatory disorders encompass a broad spectrum of disease in which the eye or its various parts may be attacked by the immune system, leading to severe visual impairment. Uveitis is the third leading cause of blindness and currently accounts for approximately 10% of preventable vision loss in the US, and up to 15% worldwide. In the recent past, tremendous progress in the treatment landscape, as well as the optimization of diagnostic monitoring tools, have made it possible to change the natural history of non-infectious uveitis, with a consequent improvement in disease-related morbidity. The ULISSE study showed that the rate of diagnoses was comparable between a standardized strategy and an open strategy. The investigations requested in the absence of guidance prove to be of very limited interest. Conversely, some simple complementary examinations have shown significant benefit. Several studies have clarified the value of investigations such as magnetic resonance imaging, nuclear imaging, and anterior chamber tap for the diagnosis. Based on the results from randomized controlled trials, the treatment of chronic non-infectious uveitis has extended to biotherapies such as adalimumab and tocilizumab. Despite these exciting progresses, treating physicians still face old and new challenges in the diagnosis and management of non-infectious uveitis and its complications. In the future, analyses of endocular specimens, combining the microbiologic techniques of multiplex PCR and the measurement of cytokine or chemokine levels, could guide the diagnosis of uveitis due to an inflammatory disease. The advent of many new different molecules represents new challenges for laboratories, where reliable tests must be identified in order to optimize the choice and monitoring of systemic treatments.

The present Special Issue aims to provide an overview of the latest research on the diagnosis and treatment of non-infectious uveitis. This Issue welcomes all types of papers on the broad spectrum of clinical characteristics, prognosis, pathophysiology, and treatment of uveitis.

Prof. Dr. Pascal Sève
Guest Editor

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Keywords

uveitis
diagnosis
behçet’s syndrome
sarcoidosis
HBA-B27 acute anterior uveitis
vogt–koyanagi–harada disease
birdshot retinochoroidopathy
systemic treatment

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Published Papers (10 papers)

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Editorial

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7 pages, 276 KiB

Open AccessEditorial

Management of Non-Infectious Uveitis, a Selection of Topical Items Updating

by Pascal Sève, Thomas El Jammal, Mathieu Gerfaud-Valentin, Laurent Kodjikian, Yvan Jamilloux and Robin Jacquot

J. Clin. Med. 2022, 11(19), 5558; https://doi.org/10.3390/jcm11195558 - 22 Sep 2022

Viewed by 1031

Abstract

First of all, we would like to thank all of the authors for their contributions and the editorial staff who enabled the achievement of this «Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges» Special Issue [...] Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

Research

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23 pages, 865 KiB

Open AccessArticle

Ocular Inflammation Induced by Immune Checkpoint Inhibitors

by Florence Chaudot, Pascal Sève, Antoine Rousseau, Alexandre Thibault Jacques Maria, Pierre Fournie, Pierre Lozach, Jeremy Keraen, Marion Servant, Romain Muller, Baptiste Gramont, Sara Touhami, Habeeb Mahmoud, Pierre-Antoine Quintart, Stéphane Dalle, Olivier Lambotte, Laurent Kodjikian and Yvan Jamilloux

J. Clin. Med. 2022, 11(17), 4993; https://doi.org/10.3390/jcm11174993 - 25 Aug 2022

Cited by 21 | Viewed by 2471

Abstract

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. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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11 pages, 638 KiB

Open AccessArticle

Development and Validation of a Bayesian Network for Supporting the Etiological Diagnosis of Uveitis

by Yvan Jamilloux, Nicolas Romain-Scelle, Muriel Rabilloud, Coralie Morel, Laurent Kodjikian, Delphine Maucort-Boulch, Philip Bielefeld and Pascal Sève

J. Clin. Med. 2021, 10(15), 3398; https://doi.org/10.3390/jcm10153398 - 30 Jul 2021

Cited by 12 | Viewed by 2097

Abstract

The etiological diagnosis of uveitis is complex. We aimed to implement and validate a Bayesian belief network algorithm for the differential diagnosis of the most relevant causes of uveitis. The training dataset (n = 897) and the test dataset (n = 154) were composed of all incident cases of uveitis admitted to two internal medicine departments, in two independent French centers (Lyon, 2003–2016 and Dijon, 2015–2017). The etiologies of uveitis were classified into eight groups. The algorithm was based on simple epidemiological characteristics (age, gender, and ethnicity) and anatomoclinical features of uveitis. The cross-validated estimate obtained in the training dataset concluded that the etiology of uveitis determined by the experts corresponded to one of the two most probable diagnoses in at least 77% of the cases. In the test dataset, this probability reached at least 83%. For the training and test datasets, when the most likely diagnosis was considered, the highest sensitivity was obtained for spondyloarthritis and HLA-B27-related uveitis (76% and 63%, respectively). The respective specificities were 93% and 54%. This algorithm could help junior and general ophthalmologists in the differential diagnosis of uveitis. It could guide the diagnostic work-up and help in the selection of further diagnostic investigations. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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10 pages, 246 KiB

Open AccessArticle

Cardiac Sarcoidosis Is Uncommon in Patients with Isolated Sarcoid Uveitis: Outcome of 294 Cases

by Mael Richard, Yvan Jamilloux, Pierre-Yves Courand, Laurent Perard, Cécile-Audrey Durel, Arnaud Hot, Carole Burillon, Isabelle Durieu, Mathieu Gerfaud-Valentin, Laurent Kodjikian and Pascal Seve

J. Clin. Med. 2021, 10(10), 2146; https://doi.org/10.3390/jcm10102146 - 15 May 2021

Cited by 4 | Viewed by 1899

Abstract

Recently, concerns have been raised about an increased risk of cardiac sarcoidosis in patients with sarcoid uveitis. While cardiac sarcoidosis has a high mortality burden, there is still a lack of precise data on this association. The objective of this study is to describe the frequency and type of cardiac complications associated with sarcoidosis of a large cohort of patients with sarcoid uveitis. We analyzed the cardiac outcomes of a monocentric retrospective cohort of consecutive adults with a diagnosis of sarcoid uveitis between January 2004 and March 2020 in a tertiary French university hospital. A total of 294 patients with a final diagnosis of sarcoid uveitis were included. At final follow-up, seven (2.4%) patients of the cohort had cardiac sarcoidosis. Cardiac sarcoidosis was more frequent among patients with previously reported systemic sarcoidosis (p = 0.008). The prevalence of cardiac sarcoidosis among patients with sarcoid uveitis is low, but patients with previously diagnosed sarcoidosis or those who develop systemic sarcoidosis during follow-up appear to be at increased risk. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

29 pages, 8298 KiB

Open AccessArticle

Uveitis as an Open Window to Systemic Inflammatory Diseases

by Thomas El Jammal, Olivier Loria, Yvan Jamilloux, Mathieu Gerfaud-Valentin, Laurent Kodjikian and Pascal Sève

J. Clin. Med. 2021, 10(2), 281; https://doi.org/10.3390/jcm10020281 - 14 Jan 2021

Cited by 18 | Viewed by 5313

Abstract

Spondyloarthritis (Spa), Behçet’s disease (BD) and sarcoidosis are major systemic inflammatory diseases worldwide. They are all multisystem pathologies and share a possible ocular involvement, especially uveitis. We hereby describe selected cases who were referred by ophthalmologists to our internal medicine department for unexplained uveitis. Physical examination and/or the use of laboratory and imaging investigations allowed to make a diagnosis of a systemic inflammatory disease in a large proportion of patients. In our tertiary referral center, 75 patients have been diagnosed with Spa (n = 20), BD (n = 9), or sarcoidosis (n = 46) in the last two years. There was a significant delay in the diagnosis of Spa-associated uveitis. Screening strategies using Human Leukocyte Antigen (HLA)-B27 determination and sacroiliac magnetic resonance imaging in patients suffering from chronic low back pain and/or psoriasis helped in the diagnosis. BD’s uveitis affects young people from both sexes and all origins and usually presents with panuveitis and retinal vasculitis. The high proportion of sarcoidosis in our population is explained by the use of chest computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography CT that helped to identify smaller hilar or mediastinal involvement and allowed to further investigate those patients, especially in the elderly. Our results confirm how in these sight- and potentially life-threatening diseases a prompt diagnosis is mandatory and benefits from a multidisciplinary approach. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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9 pages, 278 KiB

Open AccessArticle

Factors Associated with Ocular and Extraocular Recovery in 143 Patients with Sarcoid Uveitis

by Francois-Henri Bienvenu, Théophile Tiffet, Delphine Maucort-Boulch, Mathieu Gerfaud-Valentin, Laurent Kodjikian, Laurent Perard, Carole Burillon, Cécile-Audrey Durel, Arnaud Hot, Yvan Jamilloux and Pascal Seve

J. Clin. Med. 2020, 9(12), 3894; https://doi.org/10.3390/jcm9123894 - 30 Nov 2020

Cited by 8 | Viewed by 1647

Abstract

Background: Sarcoidosis is one of the leading causes of uveitis. To date, no studies have assessed the factors specifically related with recovery in ocular sarcoidosis. In this study, we aimed to determine factors associated with ocular and extraocular recovery in patients with sarcoid uveitis. Methods: A retrospective study of sarcoid uveitis, with a three-year minimum follow-up in Lyon University Hospital between December 2003 and December 2019. Patients presented biopsy-proven sarcoidosis or presumed sarcoid. Recovery was defined by a disease-free status, spontaneously or despite being off all treatments for three years or more. Results: 143 patients were included: 110 with biopsy-proven and 33 with presumed sarcoid uveitis. Seventy-one percent were women, the median age at presentation was 53 years, and 71% were Caucasian. Chronic uveitis was the main clinical presentation (75%), mostly panuveitis (48%) with bilateral involvement (82%). After a median follow-up of 83.5 months, recovery was reported in 26% of patients. In multivariable analysis, Caucasian ethnicity (p = 0.007) and anterior uveitis (p = 0.008) were significantly associated with recovery, while increased intraocular pressure was negatively associated (p = 0.039). Conclusion: In this large European cohort, one quarter of patients recovered. Caucasian ethnicity and anterior uveitis are associated with ocular and extraocular recovery. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

Review

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17 pages, 7567 KiB

Open AccessReview

Birdshot Chorioretinopathy: A Review

by Elodie Bousquet, Pierre Duraffour, Louis Debillon, Swathi Somisetty, Dominique Monnet and Antoine P. Brézin

J. Clin. Med. 2022, 11(16), 4772; https://doi.org/10.3390/jcm11164772 - 16 Aug 2022

Cited by 13 | Viewed by 4089

Abstract

Birdshot chorioretinopathy (BSCR) is a bilateral chronic inflammation of the eye with no extraocular manifestations. BSCR affects middle-aged individuals from European descent and is strongly associated with the human leucocyte antigen (HLA)-A29 allele. The immune mechanisms involved are not fully understood, but recent advances have shown the role of Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) in disease pathogenesis. Multimodal imaging, including fluorescein angiography, indocyanine angiography, fundus autofluorescence, and optical coherence tomography, are useful in confirming the diagnosis and monitoring disease activity. Visual field testing is also important to assess the disease progression. To date, there is no consensus for optimal treatment regimen and duration. Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease. Here, we will review publications focused on birdshot chorioretinopathy to give an update on the pathophysiology, the multimodal imaging, and the treatment of the disease. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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7 pages, 211 KiB

Open AccessReview

Juvenile Idiopathic Arthritis-Associated Chronic Uveitis: Recent Therapeutic Approaches

by Pierre Quartier

J. Clin. Med. 2021, 10(13), 2934; https://doi.org/10.3390/jcm10132934 - 30 Jun 2021

Cited by 13 | Viewed by 2549

Abstract

Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

21 pages, 4098 KiB

Open AccessReview

Old and New Challenges in Uveitis Associated with Behçet’s Disease

by Julie Gueudry, Mathilde Leclercq, David Saadoun and Bahram Bodaghi

J. Clin. Med. 2021, 10(11), 2318; https://doi.org/10.3390/jcm10112318 - 26 May 2021

Cited by 8 | Viewed by 5995

Abstract

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. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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36 pages, 401 KiB

Open AccessReview

Biotherapies in Uveitis

by Mathilde Leclercq, Anne-Claire Desbois, Fanny Domont, Georgina Maalouf, Sara Touhami, Patrice Cacoub, Bahram Bodaghi and David Saadoun

J. Clin. Med. 2020, 9(11), 3599; https://doi.org/10.3390/jcm9113599 - 8 Nov 2020

Cited by 36 | Viewed by 4275

Abstract

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. Full article

(This article belongs to the Special Issue Diagnosis and Management of Non-infectious Uveitis: Old and New Challenges)

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