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Clinical Advances in the Diagnosis and Treatment of Uveitis
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Clinical Advances in the Diagnosis and Treatment of Uveitis

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

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 26071

Special Issue Editor

Prof. Dr. Nicole Stuebiger

E-Mail Website
Guest Editor
Department of Ophthalmology, University of Hamburg, Hamburg, Germany
Interests: uveitis; diagnosis; new diagnostic testings; imaging; new treatment strategies; bDMARDS; small molecules
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For the last decades, there has been an increasing pace of progress in diagnosis and in new treatment options in patients who are suffering from uveitis.

Uveitis is an inflammation of the uvea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Ocular inflammation can be in the form of anterior, intermediate, posterior, or pan-uveitis, as described by the Standardization of Uveitis Nomenclature (SUN) Working Group. It affects approximately 1:4500 people, while occurring most common between the ages 20 to 60 with men and women affected equally. Even in Western countries, uveitis is estimated to be responsible for approximately 10%–20% of blindness. Evidence suggests that early diagnosis and more aggressive therapy improves ocular outcomes.

For reaching the diagnosis in uveitis patients there are several investigations including microbiological, immunological, imaging and molecular diagnostic testing, e.g., Interferon-gamma release assay (IGRA) for confirming acute or latent tuberculosis or the spectral domain optical coherence tomography (OCT) including OCT-angiography (OCTA) for imaging the retina, the choroid, and their vasculature.

Immunomodulatory therapy has been associated with control of inflammation associated with better visual outcomes. Still last century visual outcome was uncertain during treatment with conventional Disease Modyfying Antirheumatic Drugs (cDMARDs), but prognosis emerged dramatically since FDA approved in the late 1990s the first biologic drug, the TNF-alpha-blocking agent etanercept. This is a constantly expanding medication class, the biological (b)DMARDs. Inhibitors of other pro-inflammatory cytokines, e.g., the interleukin (IL)-6 blockade with tocilizumab or the B-cell depleting agent rituximab also belong to this class. Other new therapeutics that enhance anti-inflammatory cytokines (e.g. IL-10), or block small molecule signaling (phosphodiesterase and tyrosine kinase inhibition) are in development, or in use, for other inflammatory indications.

This Special Issue compiles articles that reflect the current state of the art and are also indicative of some of the anticipated advances in diagnosis and treatment in uveitis.

Prof. Dr. Nicole Stuebiger
Guest Editor

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Keywords

  • Uveitis
  • Diagnosis
  • New diagnostic testings
  • Imaging
  • New treatment strategies
  • bDMARDS
  • Small molecules

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Published Papers (8 papers)

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8 pages, 2586 KiB  
Article
X-Linked Retinoschisis Masquerading Uveitis
by Luca Mautone, Johannes Birtel, Yevgeniya Atiskova, Vasyl Druchkiv, Nicole Stübiger, Martin S. Spitzer and Simon Dulz
J. Clin. Med. 2023, 12(11), 3729; https://doi.org/10.3390/jcm12113729 - 29 May 2023
Cited by 2 | Viewed by 1650
Abstract
X-linked retinoschisis (XLRS) shows features also seen in patients with uveitis and is recognized as an uveitis masquerade syndrome. This retrospective study aimed to describe characteristics of XLRS patients with an initial uveitis diagnosis and to contrast these to patients with an initial [...] Read more.
X-linked retinoschisis (XLRS) shows features also seen in patients with uveitis and is recognized as an uveitis masquerade syndrome. This retrospective study aimed to describe characteristics of XLRS patients with an initial uveitis diagnosis and to contrast these to patients with an initial XLRS diagnosis. Patients referred to a uveitis clinic, which turned out to have XLRS (n = 4), and patients referred to a clinic for inherited retinal diseases (n = 18) were included. All patients underwent comprehensive ophthalmic examinations, including retinal imaging with fundus photography, ultra-widefield fundus imaging, and optical coherence tomography (OCT). In patients with an initial diagnosis of uveitis, a macular cystoid schisis was always interpreted as an inflammatory macular edema; vitreous hemorrhages were commonly interpreted as intraocular inflammation. Patients with an initial diagnosis of XLRS rarely (2/18; p = 0.02) showed vitreous hemorrhages. No additional demographic, anamnestic, and anatomical differences were found. An increased awareness of XLRS as a uveitis masquerade syndrome may facilitate early diagnosis and may prevent unnecessary therapies. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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14 pages, 1291 KiB  
Article
Tear and Plasma Levels of Cytokines in Patients with Uveitis: Search for Active Disease Biomarkers
by Luis García-Onrubia, Milagros Mateos Olivares, Carmen García-Vázquez, Amalia Enríquez-de-Salamanca, Lidia Cocho and José María Herreras Cantalapiedra
J. Clin. Med. 2022, 11(23), 7034; https://doi.org/10.3390/jcm11237034 - 28 Nov 2022
Cited by 5 | Viewed by 2039
Abstract
Uveitis accounts for up to 20% of blindness in Europe, making the development of new non-invasive biomarkers which could help in its management a field of interest. It has been hypothesised that tear levels of cytokines and chemokines could be used as a [...] Read more.
Uveitis accounts for up to 20% of blindness in Europe, making the development of new non-invasive biomarkers which could help in its management a field of interest. It has been hypothesised that tear levels of cytokines and chemokines could be used as a potential biomarker in patients with anterior uveitis, and this could be correlated with their concentration in plasma. Therefore, we measured twelve cytokines/chemokines in tear and plasma samples of 22 patients diagnosed with active anterior uveitis. Levels of these molecules in tears and plasma were compared and associated with the degree of activity of the uveitis. It is notable that the percentage of tear interleukin (IL)-6 detection was significantly reduced in the inactive phase (p < 0.05). However, the tear concentration in epidermal growth factor (EGF), fractalkine, IL-8, IL-1RA, interferon-inducible protein (IP)-10/CXCL10, vascular endothelial growth factor (VEGF) and IL-6, comparing the active and inactive period, was not statistically different. Apart from the tear VEGF levels, the cytokine/chemokine concentration in tears in the active/inactive phase was statistically different (p < 0.05) from the counterpart levels in plasma. In conclusion, no isolated cytokine/chemokine in the tears has been found in a concentration which could be used as a potential biomarker of disease activity and treatment response. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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8 pages, 551 KiB  
Article
Diagnostic Accuracy of Vitreous Cytology in Patients with Vitreoretinal Lymphoma
by Donghyun Lee, Junwon Lee, Ji-Hae Nahm and Min Kim
J. Clin. Med. 2022, 11(21), 6450; https://doi.org/10.3390/jcm11216450 - 31 Oct 2022
Cited by 3 | Viewed by 1597
Abstract
(1) Background: To determine the diagnostic value of vitreous cytology in patients with vitreoretinal lymphoma (VRL) and evaluate its diagnostic accuracy relative to that of other diagnostic tests. (2) Methods: In total, 38 eyes from 38 patients with VRL who underwent diagnostic vitrectomy [...] Read more.
(1) Background: To determine the diagnostic value of vitreous cytology in patients with vitreoretinal lymphoma (VRL) and evaluate its diagnostic accuracy relative to that of other diagnostic tests. (2) Methods: In total, 38 eyes from 38 patients with VRL who underwent diagnostic vitrectomy and were followed up for at least 6 months were analyzed. The clinical manifestations and VRL diagnostic rates for all diagnostic tests were determined. (3) Results: The presence of vitreous cells/opacity was the most common ophthalmic finding (97.4%), followed by sub-retinal pigment epithelial infiltration (65.8%) and retinal hemorrhage (21.1%). The VRL diagnostic rates were 89.3% for interleukin (IL)-10 levels > 50 pg/mL; 82.1% for IL-10/IL-6 ratios > 1; 60.0% and 63.3% for immunoglobulin heavy chain and kappa light chain clonality assays, respectively; and 44.4% for vitreous cytology. The VRL diagnostic rate for vitreous cytology was significantly lower in the steroid pretreatment group than in the non-steroid pretreatment group (p = 0.007). (4) Conclusions: The VRL detection rate for vitreous cytology was lower than that for the other tests, especially in patients who received steroid pretreatment. These findings suggest that even if vitreous cytology findings are negative, other tests and characteristic fundus findings should be evaluated to confirm VRL diagnosis. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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9 pages, 1280 KiB  
Article
Longitudinal Comparison of Constant Artifacts in Optical Coherence Tomography Angiography in Patients with Posterior Uveitis Compared to Healthy Subjects
by Dominika Pohlmann, Martin Berlin, Felix Reidl, Steffen Emil Künzel, Uwe Pleyer, Antonia M. Joussen and Sibylle Winterhalter
J. Clin. Med. 2022, 11(18), 5376; https://doi.org/10.3390/jcm11185376 - 13 Sep 2022
Cited by 2 | Viewed by 1347
Abstract
Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of [...] Read more.
Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of 54 patients with posterior uveitis, and an age-matched control group including 34 healthy subjects (67 eyes), were evaluated (day 0, month 3, month 6). We assigned different artifacts to distinct layers. Various types of artifacts were examined in different retinal layers. The χ2 test for the comparison between the control and uveitis group and Cochran’s Q test for the longitudinal comparison within the uveitis group were used. Results: A total of 2238 images were evaluated; 1836 from uveitis patients and 402 from healthy subjects. A total of 2193 artifacts were revealed. Projection (812 [36.3%]), segmentation (579 [25.9%]), shadowing (404 [18.1%]), and blink artifacts (297 [13.3%]) were the most common artifact types. The uveitis group displayed significantly more segmentation artifacts and projection artifacts (p < 0.001). No segmentation artifacts were documented in healthy subjects. The consecutive examinations within the uveitis group revealed the same artifact types without significance (p > 0.1). Conclusions: The uveitis patients showed more segmentation and projection artifacts than the control group. Within the uveitis group, artifacts remained longitudinally constant in terms of artifact type and pattern. The artifacts therefore appear to be reproducible on an individual level. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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19 pages, 5297 KiB  
Article
Treatment in Latent Tuberculosis Uveitis—Is Immunosuppression Effective or Is Conventional 3- or 4-Drug Antituberculosis Therapy Mandatory?
by Eileen Bigdon, Nils Alexander Steinhorst, Stephanie Weissleder, Vasyl Durchkiv and Nicole Stübiger
J. Clin. Med. 2022, 11(9), 2419; https://doi.org/10.3390/jcm11092419 - 26 Apr 2022
Cited by 7 | Viewed by 2445
Abstract
Background/Aims: Controversy exists regarding 3- or 4 drug antituberculosis therapy (conventional ATT) in uveitis patients having latent tuberculosis (LTB), especially while initiating therapy with corticosteroids and/or other immunosuppressants. Methods: We performed a monocentral retrospective analysis of posterior uveitis patients with latent TB. Latent [...] Read more.
Background/Aims: Controversy exists regarding 3- or 4 drug antituberculosis therapy (conventional ATT) in uveitis patients having latent tuberculosis (LTB), especially while initiating therapy with corticosteroids and/or other immunosuppressants. Methods: We performed a monocentral retrospective analysis of posterior uveitis patients with latent TB. Latent TB was diagnosed, in case of a positive QuantiFERON®-TB-Gold test and normal chest imaging, after ruling out other causes of infectious and noninfectious uveitis. Patients with active TB were excluded. From 2016 to 2020 we included 17 patients. Ophthalmological evaluation consisted of Best corrected visual acuity (BCVA), slit lamp examination, fundoscopy, OCT, and fluorescein- and indocyaningreen- angiography before and at months 3, 6, 12, 24, and the last follow-up after treatment. Results: Initially, all patients had active posterior uveitis with occlusive (n = 5 patients) and nonocclusive retinal vasculitis (n = 12 patients). Mean follow up was 28 ± 15 months. Therapy was started with systemic corticosteroids (mean prednisolone equivalent 71.3 mg/d) and already after 3 months it could be tapered to a mean maintenance dosage of 8.63 mg/d. Additional immunosuppressive treatment with cs- or bDMARDs was initiated in 14 patients (82%) due to recurrences of uveitis while tapering the corticosteroids <10 mg per/day or because of severe inflammation at the initial visit. While being on immunosuppression, best corrected visual acuity increased from 0.56 logMAR to 0.32 logMAR during follow-up and only three patients had one uveitis relapse, which was followed by switch of immunosuppressive treatment. As recommended, TB prophylaxis with 300 mg/d isoniazid was administered in 11 patients for at least 9 months while being on TNF-alpha-blocking agents. No patient developed active tuberculosis during immunosuppressive therapy. Conclusion: Mainly conventional ATT is strongly recommended—as monotherapy or in combination with immunosuppressives—for effective treatment in patients with uveitis due to latent TB. Although in our patient group no conventional ATT was initiated, immunosuppression alone occurred as an efficient treatment. Nevertheless, due to possible activation of TB, isoniazid prophylaxis is mandatory in latent TB patients while being on TNF-alpha blocking agents. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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11 pages, 837 KiB  
Article
Occurrence and Risk Factors for Macular Edema in Patients with Juvenile Idiopathic Arthritis-Associated Uveitis
by Christoph Tappeiner, Han Sol Bae, Kai Rothaus, Karoline Walscheid and Arnd Heiligenhaus
J. Clin. Med. 2021, 10(19), 4513; https://doi.org/10.3390/jcm10194513 - 29 Sep 2021
Cited by 3 | Viewed by 2013
Abstract
Purpose: To analyze occurrence and risk factors for macular edema (ME) in juvenile idiopathic arthritis-associated uveitis (JIA-U). Methods: Retrospective analysis of patients with JIA-U at a tertiary referral uveitis center between 2000 and 2019. Epidemiological data and clinical findings before ME onset were [...] Read more.
Purpose: To analyze occurrence and risk factors for macular edema (ME) in juvenile idiopathic arthritis-associated uveitis (JIA-U). Methods: Retrospective analysis of patients with JIA-U at a tertiary referral uveitis center between 2000 and 2019. Epidemiological data and clinical findings before ME onset were evaluated. Results: Out of 245 patients, ME developed in 41 (18%) of the 228 JIA-U patients for whom data documentation was complete during the follow-up (mean 4.0 ± 3.8 years). Risk factors (univariable logistic regression analysis) at baseline for subsequent ME onset included older age at initial documentation at institution (hazard ratio, HR 1.19, p < 0.0001), longer duration of uveitis at initial documentation (HR 1.17, p < 0.0001), worse best-corrected visual acuity (BCVA; HR 2.49, p < 0.0001), lower intraocular pressure (IOP; HR 0.88, p < 0.01), band keratopathy (HR 2.29, p < 0.01), posterior synechiae (HR 2.55, p < 0.01), epiretinal membrane formation (HR 6.19, p < 0.0001), optic disc swelling (HR 2.81, p < 0.01), and cataract (HR 4.24, p < 0.0001). Older age at initial documentation at institution (HR 1.55, p < 0.001), worse BCVA (HR 28.56, p < 0.001), and higher laser-flare photometry (LFM) values (HR 1.003, p = 0.01) were independent risk factors for ME manifestation. Patients with ME revealed significant changes in BCVA, LFM, and IOP and new optic disc swelling at 6 and 3 months before ME onset compared to timepoint of ME occurrence (p < 0.05, each). Conclusion: ME is a common complication of JIA-U. Demographic risk factors and courses of IOP, BCVA, and LFM may indicate patients at risk for ME onset. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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14 pages, 1937 KiB  
Article
Intravitreal 0.19 mg Fluocinolone Acetonide Implant in Non-Infectious Uveitis
by Muaas Hikal, Nil Celik, Gerd Uwe Auffarth, Lucy Joanne Kessler, Christian Steffen Mayer and Ramin Khoramnia
J. Clin. Med. 2021, 10(17), 3966; https://doi.org/10.3390/jcm10173966 - 1 Sep 2021
Cited by 20 | Viewed by 3026
Abstract
The efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema (UME) was assessed on twenty-six patients (34 eyes) with non-infectious UME between 2013 and 2020, in a mean follow-up of 18 ± 19.3 (mean [...] Read more.
The efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema (UME) was assessed on twenty-six patients (34 eyes) with non-infectious UME between 2013 and 2020, in a mean follow-up of 18 ± 19.3 (mean ± SD) months. Macular edema was resolved in 24 (70.6%) cases. Five of these eyes had a relapse after 23.2 ± 14 months. Three FAc reinjections were performed and a drying of the macula was observed. After FAc implantation, 24 eyes (70.6%) were completely dry; central retinal thickness (CRT) decreased in 6 eyes (17.6%), but residual intraretinal fluid was still evident. In 20 eyes (58.5%), visual acuity (VA) improved (from +1 to +5 lines) and remained stable in 9 eyes (26.5%). Thirty eyes (88.2%) were pseudophakic at baseline and four were phakic. Three of these eyes had a cataract prior to therapy and the other developed a cataract 2.5 years after the FAc implant was administered. There was an overall increase in intraocular pressure (IOP; +4.4 ± 3.7 mmHg) and eye drops were required in three eyes. The FAc implant led to long-term improvements in mean CRT and VA, and that the side-effect profile was manageable in a clinical setting in patients with non-infectious UME. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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28 pages, 16291 KiB  
Review
A Comprehensive Update on Retinal Vasculitis: Etiologies, Manifestations and Treatments
by Aniruddha Agarwal, Anne Rübsam, Lynn zur Bonsen, Francesco Pichi, Piergiorgio Neri and Uwe Pleyer
J. Clin. Med. 2022, 11(9), 2525; https://doi.org/10.3390/jcm11092525 - 30 Apr 2022
Cited by 21 | Viewed by 10576
Abstract
Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have [...] Read more.
Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging. Full article
(This article belongs to the Special Issue Clinical Advances in the Diagnosis and Treatment of Uveitis)
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