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Biomedicines
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Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation
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Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 7934

Special Issue Editor

Prof. Dr. Uwe Pleyer

E-Mail Website
Guest Editor
Center of Ocular Inflammation, Charité, Berlin, Germany
Interests: ocular immune-mediated disorders; keratitis; immune pharmacology; uveitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Intraocular inflammation remains a leading cause of visual impairment and a significant burden of legal and economic blindness. Although the molecular/immunological mechanisms of uveitis have been analyzed, leading to new findings, many details of the inflammatory processes remain unknown. Complex interactions, e.g., with regard to “new” infectious agents, the genotype of the host, and modulation of the microbiome in non-infectious uveitis are of increasing interest. The relevance of immune senescence and “inflammaging” are other interesting fields that remain uncovered. The complex immune–biologic scenario is often highly destructive and remains a challenge for early and accurate diagnosis and effective management. Therefore, the development of improved therapeutic modalities, both with intravitreal approaches as well as immune modulatory agents, has received intense attention from the uveitis research community.

The aim of this Special Issue is to provide expert insight into current diagnostic and therapeutic procedures for infectious and non-infectious uveitis. In addition, current developments regarding biomarkers for monitoring inflammation will be included. Both original papers and review articles will be considered.

Prof. Dr. Uwe Pleyer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarker
  • diagnosis
  • immune pharmacology
  • immune regulation
  • immune system
  • infection
  • uveitis
  • therapy

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Published Papers (7 papers)

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Research

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15 pages, 2909 KiB  
Article
A Meta-Analysis of the Efficacy and Safety of the 0.19 mg Fluocinolone Acetonide Implant in Non-Infectious Uveitis
by Suji Yeo, Yoo-Ri Chung, Ji Hun Song, Bahram Bodaghi and Sara Touhami
Biomedicines 2025, 13(2), 248; https://doi.org/10.3390/biomedicines13020248 - 21 Jan 2025
Viewed by 842
Abstract
Background/Objectives: The fluocinolone acetonide implant (FAI) is an intravitreal corticosteroid implant designed to have a therapeutic effect lasting up to 3 years. We performed a meta-analysis to investigate the efficacy and safety of the FAI (0.19 mg, releasing at 0.2 μg/day) in patients [...] Read more.
Background/Objectives: The fluocinolone acetonide implant (FAI) is an intravitreal corticosteroid implant designed to have a therapeutic effect lasting up to 3 years. We performed a meta-analysis to investigate the efficacy and safety of the FAI (0.19 mg, releasing at 0.2 μg/day) in patients with non-infectious uveitis. Methods: The PubMed, EMBASE, and Cochrane Library databases were last searched on 6 September 2024. Studies comparing FAI with sham injections were investigated. The primary outcome was the recurrence of uveitis. Secondary outcomes included visual acuity, intraocular pressure (IOP), and occurrence of cataracts. Results: Significantly more patients in the FAI group experienced no uveitis recurrence for up to 36 months compared to the sham group, with a relatively lower number of recurrences. Systemic adjuvant therapy was similar between groups, while fewer patients required local rescue injections in the FAI group (95% confidence interval (CI): −2.91 to −1.70). Visual acuity changes and the proportion of eyes with ≥15 letters gain were not significantly different between the groups. More patients needed cataract surgery in the FAI group (95% CI: 0.68–1.96). No differences were observed in IOP change, final IOP, or treatment-requiring events related to an increased IOP. However, more subjects experienced events of IOP > 25 mmHg with the FAI (95% CI: 0.73 to 2.14). Conclusions: The 0.19 mg FAI was effective in preventing uveitis recurrence, and reduced the need for local injections. No significant impacts were noted in terms of systemic therapy, visual improvement, or most IOP-related complications. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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12 pages, 559 KiB  
Article
Adalimumab Autoantibodies in Uveitis Patients: Do We Need Routine Drug Monitoring?
by Lynn S. zur Bonsen, Vitus A. Knecht, Anne Rübsam, Dominika Pohlmann and Uwe Pleyer
Biomedicines 2024, 12(12), 2782; https://doi.org/10.3390/biomedicines12122782 - 6 Dec 2024
Viewed by 1022
Abstract
Background: Adalimumab, an anti-TNF-α biologic agent, has emerged as a principal treatment option for patients with non-infectious uveitis. The influence of adalimumab anti-drug antibodies (AAA) on the efficacy of adalimumab therapy is not yet fully understood. We aim to understand their clinical implications [...] Read more.
Background: Adalimumab, an anti-TNF-α biologic agent, has emerged as a principal treatment option for patients with non-infectious uveitis. The influence of adalimumab anti-drug antibodies (AAA) on the efficacy of adalimumab therapy is not yet fully understood. We aim to understand their clinical implications in the context of therapeutic drug monitoring and the factors contributing to the formation of these antibodies. Methods: We conducted a retrospective analysis of 114 patients with non-infectious uveitis who developed AAA while undergoing adalimumab therapy. Results: Among the 114 AAA-positive uveitis patients, a significant correlation was observed between AAA levels and reduced adalimumab serum levels (r = −0.58, p < 0.001). The mean time to AAA detection was 2.1 years (range 0.1–11.9 years), with 45.6% of cases identified through routine testing. If AAA levels were initially low, subsequent measurements for AAA were more likely to become negative during treatment (r = 0.63, p < 0.001). Higher AAA concentrations were associated with a shorter time to detection (r = −0.27, p = 0.01) and younger age (r = −0.21, p = 0.03). There was a trend, though no significant influence, of concomitant immunosuppression with prednisolone ≤ 7.5 mg or methotrexate on antibody formation (p = 0.18). No significant difference was observed in AAA levels between uveitis subtypes. Conclusions: Higher AAA concentrations are associated with lower adalimumab serum levels in uveitis patients. Routine clinical testing is essential for optimal therapeutic drug monitoring to prevent early loss of effectiveness. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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15 pages, 2607 KiB  
Article
Choroidal Response to Intravitreal Bevacizumab Injections in Treatment-Naïve Macular Neovascularization Secondary to Chronic Central Serous Chorioretinopathy
by David Rabinovitch, Shiri Shulman, Dafna Goldenberg, Liang Wang, Prashanth Iyer, Anat Loewenstein, Noah Igra, Olivia Levine, Gissel Herrera and Omer Trivizki
Biomedicines 2024, 12(12), 2760; https://doi.org/10.3390/biomedicines12122760 - 3 Dec 2024
Viewed by 823
Abstract
Background/Objectives: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic central serous chorioretinopathy (cCSC). Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC [...] Read more.
Background/Objectives: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic central serous chorioretinopathy (cCSC). Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC complicated by MNV and treated with IVB injections over a 5-year period. The presence of MNV was confirmed using optical coherence tomography angiography (OCTA). Best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SFCT), and subretinal fluid (SRF) were recorded pre- and post-IVB treatment. Results: Twenty-two eyes of 22 patients (mean age, 68 ± 11 years) were included. After a mean follow-up of 21.0 ± 14.6 months, SRF significantly decreased from baseline (176.86 ± 115.62 µm) to the final follow-up (80.95 ± 87.32 µm, p = 0.003). A greater SRF reduction was associated with more injections (>7) (p = 0.047). However, no significant changes were observed in BCVA (p > 0.05) or SFCT (p > 0.05), irrespective of follow-up duration or injection frequency. Complete resolution of SRF was achieved in nine patients (40.9%), and a significantly greater reduction in SFCT was observed in complete responders compared to non-responders (p = 0.03). Conclusions: IVB therapy significantly reduced SRF in cCSC patients with secondary MNV, though it did not lead to visual improvement or significant changes in SFCT. However, greater choroidal thinning in patients with complete fluid resorption may suggest distinct underlying mechanisms or alternative sources of subretinal fluid beyond the MNV itself. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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14 pages, 3211 KiB  
Article
Microvascular and Structural Characterization of Birdshot Chorioretinitis in Active and Inactive Phases
by Aina Moll-Udina, Marina Dotti-Boada, Anabel Rodríguez, Maite Sainz-de-la-Maza, Alfredo Adán and Victor Llorenç
Biomedicines 2024, 12(10), 2414; https://doi.org/10.3390/biomedicines12102414 - 21 Oct 2024
Viewed by 911
Abstract
Objective: This study aimed to examine microvascular changes and identify predictors of short-term quiescence in active birdshot chorioretinitis (BSCR). Methods: An observational, prospective, 12-month follow-up cohort study was conducted. BSCR eyes were clinically assessed at baseline, categorized as active or inactive, and reevaluated [...] Read more.
Objective: This study aimed to examine microvascular changes and identify predictors of short-term quiescence in active birdshot chorioretinitis (BSCR). Methods: An observational, prospective, 12-month follow-up cohort study was conducted. BSCR eyes were clinically assessed at baseline, categorized as active or inactive, and reevaluated at 12 months. Based on their clinical activity at both timepoints, eyes were divided into three subgroups: active-to-inactive (A-I), consistently active (A-A), and consistently inactive (I-I). Structural OCT, OCT-angiography (OCT-A), and ultra-widefield imaging were utilized. Exam data from fundus and nasal subfields were analyzed for microvascular changes and quiescence predictors. Results: Sixty eyes from 30 BSCR patients (47% women, 53% men, mean age 59.7 ± 12.3 years) were included. In the A-I group (16 eyes), vascular density and perfusion indices increased in all subfields post-quiescence, contrasting with the other groups. Perifoveal looping in the superficial capillary plexus predicted quiescence at 12 months compared with the A-A group. Conclusions: Vascular density rises after complete inflammation control in BSCR, and perifoveal capillary loops serve as potential predictors of short-term quiescence in active BSCR. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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10 pages, 2048 KiB  
Article
Long-Term Functional Outcomes of Retinal Detachment Due to Acute Retinal Necrosis: A Case Series
by Ludovico Iannetti, Giacomo Visioli, Ludovico Alisi, Marta Armentano, Maria Pia Pirraglia, Massimo Accorinti, Valerio Di Martino and Magda Gharbiya
Biomedicines 2024, 12(10), 2320; https://doi.org/10.3390/biomedicines12102320 - 11 Oct 2024
Viewed by 1212
Abstract
Objectives: To evaluate the long-term anatomical and functional prognosis of patients with retinal detachment (RD) secondary to acute retinal necrosis (ARN) treated with pars plana vitrectomy (PPV). Methods: This retrospective case series included 21 eyes from 21 patients with RD secondary [...] Read more.
Objectives: To evaluate the long-term anatomical and functional prognosis of patients with retinal detachment (RD) secondary to acute retinal necrosis (ARN) treated with pars plana vitrectomy (PPV). Methods: This retrospective case series included 21 eyes from 21 patients with RD secondary to ARN. The study analyzed vitreous or aqueous biopsy results, the impact of antiviral therapy, time to retinal detachment, changes in visual acuity (VA), and anatomical and surgical outcomes. All cases underwent 23-gauge PPV with silicone oil tamponade, and an episcleral encircling band was used in 11 cases. All patients received systemic antiviral therapy at diagnosis. Results: Retinal reattachment was achieved in 91% of cases during follow-up, with an average follow-up period of 39.5 ± 36.8 months. The average time from ARN diagnosis to RD onset was 33.3 ± 27.5 days. VZV was detected in 10 eyes through PCR analysis. Significant differences in visual prognosis were found between macula-off and macula-on RD (p = 0.048). Eyes with optic nerve head inflammation had worse final VA (p = 0.010). No significant difference was observed between preoperative VA and VA at the end of follow-up (p = 0.665). Conclusions: VZV was the primary virus associated with ARN-related RD. Early involvement of the macula and optic nerve in retinitis negatively impacted the final visual prognosis. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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Review

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16 pages, 2069 KiB  
Review
Retinopathy of Prematurity and MicroRNAs
by Giuseppe Maria Albanese, Giacomo Visioli, Ludovico Alisi, Marta Armentano, Francesca Giovannetti, Luca Lucchino, Marco Marenco, Paola Pontecorvi and Magda Gharbiya
Biomedicines 2025, 13(2), 400; https://doi.org/10.3390/biomedicines13020400 - 7 Feb 2025
Cited by 1 | Viewed by 981
Abstract
Retinopathy of Prematurity (ROP), a leading cause of blindness in preterm infants, arises from dysregulated angiogenesis and inflammation. Without timely intervention, ROP can progress to severe outcomes, including dense fibrovascular plaques and retinal detachment. MicroRNAs (miRNAs) regulate key pathways such as hypoxia response, [...] Read more.
Retinopathy of Prematurity (ROP), a leading cause of blindness in preterm infants, arises from dysregulated angiogenesis and inflammation. Without timely intervention, ROP can progress to severe outcomes, including dense fibrovascular plaques and retinal detachment. MicroRNAs (miRNAs) regulate key pathways such as hypoxia response, VEGF signaling, and vascular remodeling. Studies have identified miRNAs (e.g., miR-210, miR-146a, and miR-21) as potential biomarkers and therapeutic targets. Preclinical evidence supports miRNA-based therapies (e.g., miR-18a-5p and miR-181a), targeting HIF-1α and VEGFA to mitigate neovascularization, with nanoparticle delivery systems enhancing stability and specificity. These strategies, combined with anti-VEGF agents, show significant potential for improving ROP management. While promising, miRNA therapies require validation in clinical trials to ensure safety and efficacy. This review discusses the role of miRNAs in ROP, highlighting their relevance as diagnostic and therapeutic tools. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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15 pages, 1458 KiB  
Review
A Comprehensive Review of Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome
by Alexandra Bograd, Arnd Heiligenhaus, Stefan Reuter and Christoph Tappeiner
Biomedicines 2025, 13(2), 300; https://doi.org/10.3390/biomedicines13020300 - 26 Jan 2025
Viewed by 1398
Abstract
Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This [...] Read more.
Background: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disorder, characterized by acute tubulointerstitial nephritis and uveitis. It poses diagnostic challenges due to the mostly asynchronous onset of renal and ocular manifestations, as well as the variety of differential diagnoses. This review provides an overview of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management strategies. Methods: A comprehensive review of the peer-reviewed literature, including studies and case reports, was conducted. Results: The etiology of TINU syndrome involves an autoimmune reaction to renal and ocular antigens, leading to interstitial inflammation and tubular damage in the kidneys, and anterior uveitis with acute onset of flares. Diagnostic criteria based on ocular examination, laboratory parameters, and renal biopsy emphasize the need to exclude other systemic diseases. TINU syndrome accounts for approximately 2% of all uveitis cases. Primary treatment consists of corticosteroids, while immunomodulatory therapies (methotrexate, azathioprine, mycophenolate mofetil, or biologic agents) are reserved for refractory cases. Recurrence of uveitis appears to be more common than that of nephritis. Conclusions: TINU syndrome is rare and requires clinical suspicion for accurate diagnosis. Early diagnosis and initiation of treatment are crucial for achieving favorable outcomes. Advances in the understanding of its pathogenesis and treatment have improved patient outcomes. Further research is needed to investigate the underlying triggers and mechanisms in order to develop targeted therapies. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Therapeutic Strategies in Intraocular Inflammation)
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