Search Results (73)

Uveitis constitutes a heterogeneous group of intraocular inflammatory pathologies, including both infectious and non-infectious aetiologies, often leading to substantial morbidity and permanent loss of vision in up to 20% of the affected cases. Visual impairment is most prominent in intermediate, posterior, or panuveitis and is commonly associated with cystoid macular oedema, epiretinal membranes, macular holes, and retinal detachment. In the context of uveitis, these complications arise as a result of recurrent flare-ups or chronic inflammation, contributing to cumulative ocular damage. Pars plana vitrectomy (PPV) has an evolving role in the diagnostic and therapeutic approach to uveitis. Diagnostic PPV allows for the analysis of vitreous fluid and tissue using techniques such as PCR, flow cytometry, cytology, and cultures, providing further insights into intraocular immune responses. Therapeutic PPV can be employed for the management of structural complications associated with uveitis, in a wide spectrum of inflammatory clinical entities such as Adamantiades–Behçet disease, juvenile idiopathic arthritis, acute retinal necrosis, or ocular toxoplasmosis. Modern small-gauge and minimally invasive techniques improve visual outcomes, reduce intraocular inflammation, and may decrease reliance on systemic immunosuppression. Emerging technologies, including robot-assisted systems, are expected to enhance surgical precision and safety in the future. Despite these advances, PPV outcomes remain variable due to heterogeneity in indications, surgical techniques, and postoperative management. Prospective studies with standardized protocols, detailed subgroup analyses, and the integration of immunological profiling are needed to define which patients benefit most, optimize therapeutic strategies, and establish predictive biomarkers in uveitis management. Full article

Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity between cerebrospinal fluid (CSF) and aqueous humor, this study evaluated the diagnostic utility of a commercially available CSF multiplex PCR panel for detecting herpesviruses in patients with suspected viral uveitis. Methods: We retrospectively reviewed the medical records of patients whose aqueous humor samples were analyzed using a multiplex PCR assay originally designed for CSF testing (Seeplex Meningitis-V1 ACE Detection kit, Seegene, Seoul, Republic of Korea). The samples were obtained between May 2019 and June 2023 at two tertiary referral hospitals. The assay targeted herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). Patients were classified into three groups: (I) anterior uveitis with suspected herpesviral infection, (II) acute retinal necrosis (ARN), and (III) CMV retinitis. Baseline characteristics, PCR positivity rates, and virus prevalence were compared among the groups. Results: Among 149 eyes tested, 86 were included in the final analysis. The overall positivity rate was 38.4%. PCR positivity was 19.7% (12/61) in Group I, 93.8% (15/16) in Group II, and 66.7% (6/9) in Group III. CMV was the most common pathogen in Groups I (66.7%) and III (100%), while VZV was predominant in Group II (80%). No HHV-6 infection was detected. Conclusions: The positivity rate in anterior uveitis (Group I) was lower than previously reported, likely due to the limited sample volume relative to the assay’s requirement. Nevertheless, the assay demonstrated diagnostic reliability comparable to previous reports for ARN and CMV retinitis. Therefore, the CSF-based multiplex PCR panel serves as a feasible and cost-effective diagnostic option for sight-threatening posterior segment infections, facilitating prompt diagnosis and treatment, although further optimization is warranted for anterior uveitis. Full article

Ocular Toxoplasmosis (OT), a leading cause of infectious posterior uveitis, presents significant diagnostic challenges in atypical cases due to phenotypic overlap with other retinochoroiditides and a reliance on expert interpretation of multimodal imaging. This scoping review systematically maps the burgeoning application of artificial intelligence (AI), particularly deep learning, in automating OT diagnosis. We synthesized 22 studies to characterize the current evidence, data landscape, and clinical translation readiness. Findings reveal a field in its nascent yet rapidly accelerating phase, dominated by convolutional neural networks (CNNs) applied to fundus photography for binary classification tasks, often reporting high accuracy (87–99.2%). However, development is critically constrained by small, imbalanced, single-center datasets, a near-universal lack of external validation, and insufficient explainable AI (XAI), creating a significant gap between technical promise and clinical utility. While AI demonstrates strong potential to standardize diagnosis and reduce subjectivity, its path to integration is hampered by over-reliance on internal validation, the “black box” nature of models, and an absence of implementation strategies. Future progress hinges on collaborative multi-center data curation, mandatory external and prospective validation, the integration of XAI for transparency, and a focused shift towards developing AI tools that assist in the complex differential diagnosis of posterior uveitis, ultimately bridging the translational chasm to clinical practice. Full article

Toxoplasma gondii is the most common infectious cause of posterior uveitis in immunocompetent adults. While the parasite is typically acquired through ingestion of undercooked meat or contaminated food and water, unpasteurized goat milk has been identified as a less frequent but plausible source of infection. Coinfections in ocular toxoplasmosis are rare, and the role of Epstein–Barr virus (EBV) in these coinfections remains poorly understood. We report the case of a 70-year-old immunocompetent male presenting with severe, refractory panuveitis in the left eye. Initial serologic testing confirmed acquired Toxoplasma gondii infection, and treatment was initiated with systemic antimicrobials and corticosteroids. Intraocular inflammation persisted despite sequential therapy with trimethoprim–sulfamethoxazole, clindamycin, and azithromycin, eventually requiring pars plana vitrectomy with intravitreal clindamycin and dexamethasone due to non-clearing vitreous hemorrhage. Vitreous PCR testing revealed intraocular concurrent detection of EBV DNA, prompting combined antimicrobial and antiviral therapy. Epidemiological history revealed recent consumption of unpasteurized goat milk, suggesting a potential oral transmission route for Toxoplasma gondii. Although visual acuity improved following surgical intervention and targeted therapy, it remained markedly compromised due to the severity of the disease. This case illustrates the diagnostic value of multiplex PCR in refractory uveitis, enabling the detection of Toxoplasma gondii and the concurrent detection of EBV DNA in an immunocompetent patient. It highlights the importance of early molecular testing and detailed epidemiological assessment, including atypical transmission routes such as unpasteurized goat milk. Full article

A herd of approximately 300 Spanish meat goats in central Alabama experienced sporadic ocular, respiratory, and reproductive diseases over two years, prompting diagnostic investigation at Auburn University’s JT Vaughan Large Animal Teaching Hospital. Five representative doelings exhibiting ocular lesions were examined. Clinical signs included conjunctivitis, corneal opacity, uveitis, and, in one severe case, systemic illness. Initial treatment with topical and systemic antibiotics provided incomplete resolution, raising suspicion of infectious keratoconjunctivitis of atypical etiology. Comprehensive diagnostic testing was performed, including aerobic and Mycoplasma cultures, Giemsa staining, and molecular assays. Moraxella bovoculi was cultured; however, Giemsa staining revealed Chlamydia elementary bodies, and a FRET-qPCR with DNA sequencing confirmed high Chlamydia pecorum loads (up to 1.1 × 10⁷ copies/swab). Mycoplasma testing was negative. Extended treatment with systemic and topical oxytetracycline led to gradual clinical improvement, with C. pecorum DNA declining over 22,000-fold and becoming undetectable after five weeks. This case represents the first documented report of C. pecorum–associated keratoconjunctivitis in goats in the United States. The findings underscore the diagnostic importance of molecular assays for detecting intracellular pathogens that may be missed by culture. The protracted treatment course highlights the therapeutic challenges posed by chlamydial infections due to their intracellular persistence. Additionally, the concurrent detection of M. bovoculi suggests the potential for mixed infections influencing disease severity. These results emphasize C. pecorum as an emerging pathogen of caprine ocular disease with implications for herd health and management. Full article

Climate change and the El Niño Southern Oscillation (ENSO) events have been increasingly linked to infectious disease outbreaks. While growing evidence has connected climate variability with systemic illnesses, the ocular implications remain underexplored. This study aimed to assess the relationships between ENSO-driven climate events and infectious diseases with ophthalmic consequences. A narrative review of 255 articles was conducted, focusing on infectious diseases influenced by ENSO and their associated ocular findings. 39 articles met criteria for full review, covering diseases such as dengue, zika, chikungunya, malaria, leishmaniasis, leptospirosis, and Rift Valley fever. Warmer temperatures, increased rainfall, and humidity associated with ENSO events were found to enhance vector activity and disease transmission. Ocular complications included uveitis, retinopathy, and optic neuropathy, but the specific disease findings varied by infectious disease syndrome. The climactic variable changes in response to ENSO events differed across diseases and regions and were influenced by geography, local infrastructure, and socioeconomic factors. ENSO event-related climate shifts significantly impact the spread of infectious diseases with ocular symptoms. These findings highlight the need for region-specific surveillance and predictive models that may provide insight related to the risk of ophthalmic disease during ENSO events. Further research is needed to clarify long-term ENSO effects and develop integrated strategies for systemic and eye disease detection, prevention, and management. Full article

Background: Uveitis encompasses a broad group of diseases with infectious and non-infectious etiologies, potentially leading to permanent and irreversible visual impairment. This study aimed to determine whether the etiology and anatomical location of uveitis influence the course and laterality of the disease. Methods: This retrospective observational study included patients with uveitis treated at the University Eye Clinic of “St. George” University Hospital in Plovdiv, Bulgaria, between January 2011 and December 2023. All participants underwent a comprehensive eye examination and minimal laboratory screening, with additional tests and specialist consultations performed when necessary. Uveitis cases were categorized into anterior, intermediate, posterior, and panuveitis according to anatomical location; unilateral or bilateral according to laterality; and acute, chronic, or recurrent based on disease course. Results: The study included 606 patients aged between 3 and 87 years. The etiology and anatomical location of uveitis were significantly associated with the course and laterality of the disease (p < 0.001). Anterior and posterior uveitis were mostly unilateral, with a defined cause and characterized by acute or recurring progression. Intermediate uveitis was mostly idiopathic and chronic, while panuveitis had a more uniform distribution regarding disease progression. Among cases with a determined etiology, HLA-B27-associated uveitis was the most common (32.5%), characterized by sequential involvement of both eyes and a recurrent course. Viral and toxoplasmic uveitis were more frequently unilateral. Conclusions: Our findings indicate that the etiology and anatomical location of uveitis can serve as prognostic factors for contralateral eye involvement and the progression of the inflammatory process. We found that anterior and posterior uveitis were predominantly unilateral and typically presented with an acute or recurrent course, whereas intermediate uveitis and panuveitis were more commonly chronic. In men, uveitis more often had an acute onset, while in women, it tended to follow a chronic course. Full article

Background: Infectious uveitis is a potentially sight-threatening condition that requires timely and accurate pathogen identification to guide effective therapy. However, conventional microbiological tests (CMTs) often lack sensitivity and the inclusiveness of pathogen detection. Metagenomic next-generation sequencing (mNGS) offers an unbiased approach to detecting a broad range of pathogens. This review evaluates its diagnostic performance in detecting infectious uveitis. Methods: A systematic search across multiple databases identified studies assessing the use of mNGS for diagnosing infectious uveitis. The included studies compared mNGS to CMTs, including polymerase chain reaction (PCR), culture, serology, and the IGRA (Interferon-Gamma Release Assay). The study characteristics; the detection rates; and the sensitivity, specificity, and predictive values were extracted. The sensitivity and specificity of mNGS were calculated using CMTs as a reference. Results: Twelve studies comprising 859 patients were included. The sensitivity of mNGS compared to that of CMTs ranged from 38.4% to 100%, while specificity varied between 15.8% and 100%. The commonly detected pathogens included varicella-zoster virus, cytomegalovirus, Toxoplasma gondii, and herpes simplex virus. In some cases, mNGS outperformed PCR in viral detection, aiding diagnosis when the standard methods failed. However, contamination risks and inconsistent diagnostic thresholds were noted. Conclusions: mNGS enables the diagnosis of infectious uveitis, particularly for viral causes, but its variable performance and standardization challenges warrant further investigation. Full article

Background/Objectives: Chronic macular edema (CME) is a common complication of diabetic retinopathy or non-infectious uveitis affecting the posterior segment (NIU-PS). Alongside anti-VEGF therapy, glucocorticoids are frequently used to manage CME. Given the heterogeneous nature of patients’ medical history, their social conditions, and disease manifestations, individualized treatment is essential for optimal outcomes. This study assesses the effectiveness of intravitreal fluocinolone acetonide (FA) (Iluvien^®) in treating persistent and recurrent macular edema in clinical practice at the University Hospital of Erlangen–Nuremberg, Germany. Methods: A total of 46 eyes with diabetic macular edema (DME) (21 eyes) and NIU-PS (25 eyes) were retrospectively analyzed over a follow-up period of up to 36 months. Since persistent retinal thickness fluctuations are linked to long-term retinal damage and functional decline, this study analyzed central retinal thickness (CRT)—including its fluctuations measured as CRT amplitude—alongside BCVA as the primary outcomes. Results: After an initial decrease in CRT in the first year after FA treatment, the maximum CRT amplitude significantly decreased in the following years. For patients with DME, CRT amplitude reduced from 271.4 µm to 91.57 µm in the first year (p = 0.0056) and 106.0 µm in the second year (p = 0.0109). For patients with NIU-PS, CRT amplitude decreased from 185.2 µm to 87.7 µm in the first year (p = 0.0131) and 97.3 µm in the second year (p = 0.0375). Mean BCVA remained stable in both cohorts. Conclusions: Intravitreal FA proved to be effective in reducing and stabilizing CRT in patients with chronic DME and NIU-PS without losing visual acuity, reducing treatment burden. Full article

Background/Objectives: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat. Methods: Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst. Results: ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment. Conclusions: Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments. Full article

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

Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain proteins, nucleic acids and other molecules. Produced by virtually all cell types, they travel throughout the body until they reach their target, where they can trigger a wide variety of effects by transferring the molecular cargo to recipient cells. In the context of ocular physiology, exosomes play a very important role in embryological development, the regulation of homeostasis and the immune system, which is crucial for normal vision. Consequently, in pathological situations, exosomes also undergo modifications in terms of quantity, composition and content, depending on the etiology of the disease. However, the mechanisms by which exosomes contribute to ocular pathology has not yet been studied in depth, and many questions remain unanswered. This review aims to summarize the most recent knowledge on the function of exosomes in the ocular system in healthy individuals and the role they play during pathological processes of a degenerative, infectious, neurodegenerative, vascular and inflammatory nature, such as keratoconus, keratitis, glaucoma, diabetic retinopathy and uveitis. Furthermore, given their unique characteristics, their potential as diagnostic biomarkers or therapeutic agents and their application in clinical ophthalmology are also explored, along with the main limitations that researchers face today in the field. Full article

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

Background: The leading cause of blindness due to non-infectious uveitis is cystoid macular edema (CME). Behçet’s disease (BD) is one of the most commonly conditions related to CME. Objectives: To compare the effectiveness and safety of adalimumab (ADA), infliximab (IFX) and certolizumab (CZP) in refractory CME due to BD. Methods: Multicenter study of BD-CME patients with no response to glucocorticoids (GCs) and at least one conventional immunosuppressive drug. At baseline, all patients presented CME, defined by OCT > 300 µ. The effectiveness of ADA, IFX and CZP was assessed over a 2-year period from baseline using the following ocular parameters: macular thickness (µm), visual acuity (BCVA), anterior chamber (AC) cells and vitritis. Mixed-effects regression models were applied. Results: a total of 50 patients (75 eyes) were studied (ADA = 25; IFX = 15 and CZP = 10). No significant differences in demographic parameters were found among the three groups. However, individuals in the CZP group had a significantly extended time from diagnosis to treatment onset (72 (36–120) months, p = 0.03) and had received a higher number of biological therapies (1.7 ± 1.1) compared to the ADA and IFX groups. Within the CZP group, ADA and IFX were previously administrated in seven patients. After 2 years of follow-up, a rapid and sustained reduction in macular thickness was noted in all three groups with no significant differences between them. Additionally, enhancements in BCVA, AC cells and vitritis were also observed. No serious adverse events were reported in the CZP group, although one isolated case of bacteremia was documented in the ADA group. ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Conclusions: ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Full article