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IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
(Frontiers Media SA, 2025-05-13)
Rodrigo A. Valenzuela
;
Fabian Vega-Tapia
;
Nathaly Elizalde
;
Ivan Flores
;
Felipe M. Rojas
Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
Scopus© Citations 6 1
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Interpretable multimodal classification for age-related macular degeneration diagnosis
(2024)
Carla Vairetti
;
Sebastián Maldonado
;
Loreto Cuitino
;
URZUA SALINAS, CRISTHIAN
;
Xu Yanwu
<jats:p>Explainable Artificial Intelligence (XAI) is an emerging machine learning field that has been successful in medical image analysis. Interpretable approaches are able to “unbox” the black-box decisions made by AI systems, aiding medical doctors to justify their diagnostics better. In this paper, we analyze the performance of three different XAI strategies for medical image analysis in ophthalmology. We consider a multimodal deep learning model that combines optical coherence tomography (OCT) and infrared reflectance (IR) imaging for the diagnosis of age-related macular degeneration (AMD). The classification model is able to achieve an accuracy of 0.94, performing better than other unimodal alternatives. We analyze the XAI methods in terms of their ability to identify retinal damage and ease of interpretation, concluding that grad-CAM and guided grad-CAM can be combined to have both a coarse visual justification and a fine-grained analysis of the retinal layers. We provide important insights and recommendations for practitioners on how to design automated and explainable screening tests based on the combination of two image sources.</jats:p>
Scopus© Citations 1
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Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role
(2023)
Carl P. Herbort
;
Masaru Takeuchi
;
Ioannis Papasavvas
;
Ilknur Tugal-Tutkun
;
Alireza Hedayatfar
<jats:p>Background: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. Purpose: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. Methods: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. Results: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were “complementary to dye methods”, “adjunct”, “supplementing” and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. Conclusion: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.</jats:p>
7Scopus© Citations 13
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Successful treatment of cytomegalovirus retinitis with oral/intravitreal antivirals in HIV-negative patients with lymphoma
(2022)
Anastasia Tasiopoulou
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URZUA SALINAS, CRISTHIAN
;
Susan Lightman
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Objectives</jats:title> <jats:p>To report patients with systemic lymphoma and cytomegalovirus (CMV) retinitis, treated with a combination of oral and intravitreal antiviral agents on an outpatient basis.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Retrospective cases series. Information was gathered from the database of the Uveitis clinics at Moorfields Eye Hospital, United Kingdom from December 2014 to December 2018. The inclusion criteria comprised the diagnosis of systemic lymphoma, associated with a diagnosis of CMV retinitis. Exclusion criteria were alternative ocular diagnosis, human immunodeficiency virus (HIV), primary intraocular lymphoma, or other causes of immunosuppression.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>All seven subjects had been under oncologist care for systemic lymphoma. CMV retinitis presented with a median of 61 months after the systemic lymphoma diagnosis. Five patients underwent a vitreous biopsy, and four of them returned PCR positive for CMV and the fifth patient had PCR positive in a blood sample. All patients were treated with oral Valganciclovir, with an induction dose of 900 mg every 12 h for up to 3 weeks until disease resolution and a maintenance dose thereafter. All but one received additional intravitreal Foscarnet injections, with a dose of 2.4 mg /0.1 ml.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The management of patients with systemic lymphoma and CMV retinitis with oral and intravitreal antiviral agents, resulted in effective disease control.</jats:p> </jats:sec>
1Scopus© Citations 6
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Pattern ERGs suggest a possible retinal contribution to the visual acuity loss in acute optic neuritis
(2022)
I. Kleerekooper
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L. Del Porto
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L. Dell’Arti
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J. Guajardo
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S. Leo
7Scopus© Citations 6
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“White dot syndromes”, an inappropriate and outdated misnomer
(2021)
Piergiorgio Neri
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Carl P. Herbort
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Alireza Hedayatfar
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Ilknur Tugal-Tutkun
;
Luca Cimino
15Scopus© Citations 11
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Vogt-Koyanagi-Harada disease: the step-by-step approach to a better understanding of clinicopathology, immunopathology, diagnosis, and management: a brief review
(2022)
Cristhian A. Urzua
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Carl P. Herbort
;
Masaru Takeuchi
;
Ariel Schlaen
;
Luz E. Concha-del-Rio
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Appraisals of Vogt-Koyanagi-Harada disease (VKH) have become progressively more complete, since its first description in 1906. The availability of new investigational methods has improved our knowledge of the immunopathology, clinicopathology, diagnosis, and management of VKH disease. This review aimed to describe some of the steps that led to better characterization of VKH as a clinical entity.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We searched on PubMed for articles that described the history of VKH disease and analyzed the progress in disease appraisal with new investigational and imaging methods. In particular, we searched for articles that investigated the clinicopathology, diagnosis, and management of VKH.</jats:p> </jats:sec><jats:sec> <jats:title>Findings</jats:title> <jats:p>The following developments were considered essential for improving the appraisal and understanding of VKH: (1) the history of the disease, (2) immunopathological mechanisms, (3) clinicopathology, (4) the importance of distinguishing initial-onset from chronic disease, (5) relevant imaging modalities, among which indocyanine green angiography is crucial, (6) diagnostic criteria that facilitate early diagnosis, and (7) the need for early, prolonged, aggressive treatment that combines steroidal and non-steroidal immunosuppression.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Based on these findings, the definition of VKH has improved. VKH disease starts in the choroidal stroma and later involves other structures when it is not diagnosed and treated early. Indocyanine green angiography and enhanced depth imaging optical coherence tomography facilitate early diagnosis and precise monitoring of choroidal inflammation. ICGA is clearly the gold standard for appraisals and follow-ups in VKH disease, however EDI-OCT should be especially considered in those areas where ICGA is not fully available. These modalities have contributed substantially to a “cure” for VKH, when treatment is introduced within the therapeutic window of opportunity.</jats:p> </jats:sec>
Scopus© Citations 25 1
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Diagnosis and classification of optic neuritis
(2022)
Axel Petzold
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Clare L Fraser
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Mathias Abegg
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Raed Alroughani
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Daniah Alshowaeir
Scopus© Citations 81 2
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Precise, simplified diagnostic criteria and optimised management of initial-onset Vogt–Koyanagi–Harada disease: an updated review
(2021)
Carl P. Herbort
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Ilknur Tugal-Tutkun
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Ahmed Abu-El-Asrar
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Amod Gupta
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Masaru Takeuchi
17Scopus© Citations 44
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Definition of Uveitis Refractory to Treatment: A Systematic Review in the Absence of a Consensus
(2020)
Rodrigo A. Valenzuela
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Iván Flores
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Myriam Pujol
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Carolina Llanos
;
Ester Carreño
3Scopus© Citations 10

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