Ocular Immunology and Inflammation最新文献

Objectives: Non-infectious uveitis (NIU) is an immune-mediated, vision-threatening disease often requiring immunomodulatory therapy. We systematically evaluate the efficacy and safety of immunomodulatory therapies for the management of NIU.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched up to December 2024. Randomized, controlled trials (RCTs) assessing the efficacy and safety of immunomodulatory agents for uveitis were included. Bayesian network meta-analyses were conducted to compare treatments across trials, while frequentist meta-analyses were performed to estimate the absolute treatment failure rate at month 6 and the overall SAEs rate. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool.

Results: Sixteen randomized controlled trials, involving 11 immunomodulatory therapies, were included from 6097 records retrieved. Among them, adalimumab plus corticosteroids was associated with significant reduction in hazard of treatment failure over time (HR 0.51, 95% CrI: 0.24-0.95) compared with corticosteroids monotherapy. The estimated overall treatment failure rate at month 6 was 37.6%, and the number of SAE was around 10.1%. No significant differences were observed in treatment failure rates at month 6, changes in BCVA or number of SAEs across treatments.

Conclusions: Adalimumab plus corticosteroids significantly prolonged the relapse-free period compared with corticosteroids monotherapy. Mycophenolic acid showed favorable trend in both efficacy and safety. Despite immunomodulatory treatment, the risk of uveitis relapse still remains and warrants continued attention.

Purpose: To explore the clinical characteristics of moxifloxacin-associated bilateral acute iris transillumination (BAIT) and provide references for diagnosis and treatment.

Methods: The clinical reports of moxifloxacin-associated BAIT were collected before August 31, 2025, and the clinical data were extracted for retrospective analysis.

Results: A total of 40 patients were included, with a median age of 53 (range 26, 77), including 28 (70.0%) women. The median occurrence time of BAIT was 14 days (rang 0.2, 60). Patients may present with photophobia (75.0%), decreased vision (67.5%), ocular pain (50.0%), and high intraocular pressure (32.5%). Ophthalmic examination shows iris transillumination. After the patients discontinued moxifloxacin and received topical steroids and anti-glaucoma treatment, the symptoms of most patients improved, while transillumination remained.

Conclusions: The patient developed ocular symptoms such as photophobia, ocular pain and decreased vision during the use of moxifloxacin, which requires further examination. If iris transillumination, ocular hypertension and acute pigment dispersion of the iris pigment epithelium are found during ophthalmic examination, the possibility of BAIT should be considered.

Purpose: To present a case series of three immunocompromised patients (four eyes) with polymerase chain reaction (PCR)-confirmed ocular toxoplasmosis treated with intravitreal clindamycin (IVC).

Methods: Clinical data from three immunocompromised patients with atypical ocular toxoplasmosis treated with IVC were retrospectively reviewed. Diagnosis was confirmed by aqueous humor PCR, which tested positive for Toxoplasma gondii and negative for herpesviruses. Clinical outcomes were evaluated using multimodal imaging, including fundus autofluorescence (FAF).

Results: All patients presented with progressive vision loss, with T. gondii infection confirmed following initial misdiagnoses. The case series included: (1) a 56-year-old cardiac transplant recipient on immunosuppressive therapy; (2) a 47-year-old male with dermatomyositis on oral prednisone; and (3) a 56-year-old female with suspected dermatomyositis previously treated with corticosteroids, which had been discontinued one month prior to symptom onset. PCR positivity enabled targeted IVC therapy, adjunctive or substitute for systemic treatment, effectively controlling intraocular infection in all cases. FAF was valuable in follow-up, revealing subclinical progression of hyperautofluorescent lesions in some cases. Despite successful inflammation control, delayed diagnosis and advanced disease at presentation led to irreversible visual impairment in all patients.

Conclusion: Aqueous humor PCR is essential for diagnosing atypical ocular toxoplasmosis in immunocompromised patients. IVC appears well tolerated and may serve as adjunctive therapy or monotherapy when systemic treatment is not tolerated. Despite a small sample size, findings highlight the importance of early diagnosis to prevent irreversible retinal damage. FAF may aid in detecting subclinical activity throughout the disease course.

Purpose: To describe differences in the expression of selected host biomarkers, by analysing the aqueous humour (AH), cerebrospinal fluid (CSF) and serum of patients with ocular syphilis, both with and without neurosyphilis and HIV infection, to support the diagnosis of ocular syphilis.

Methods: A prospective observational descriptive study was conducted at Tygerberg Academic Hospital in Cape Town, South Africa, from February 1, 2018, to January 31, 2021. The study included all patients aged 18 years or older who presented to the eye clinic with ocular syphilis, provided they had a positive serum Treponema pallidum antibodies (TPA) test, an RPR titre of ≥ 8 and confirmed ocular inflammation. The HIV status of each patient was determined and the CRP, IL-2, IL-6, IL-10, IL-12 p70, MIP-1$\beta$ and IFN-$\gamma$ were measured in their AH, CSF and serum samples using a multiplex immunoassay platform. All patients received treatment.

Results: The mean concentrations of biomarkers IL-2, IL-10, MIP-1$\beta$, IL-6, IL-12 p70 and IFN-$\gamma$ were consistently higher in the AH compared to the CSF and serum in patients with ocular syphilis, irrespective of their HIV status and the presence or absence of concurrent neurosyphilis.

Conclusion: Our findings showed significant differences in certain cytokine levels across the AH, CSF, and serum, with notably higher concentrations in the AH. This indicates that ocular syphilis triggers a unique immune response within the eye. As a result, further analysis of AH biomarkers is needed to determine if these may enhance the diagnosis of ocular and neurosyphilis.

Purpose: The IL-6 R/JAK/STAT3 signaling pathway is implicated in non-infectious uveitis-associated macular edema, and its inhibition using monoclonal anti-IL-6 receptor therapy has been associated with clinical improvement. However, the underlying pathogenic mechanisms remain unclear. In this study, we investigated the pathological effects of a STAT3 gain-of-function (GOF) variant p.L387R identified in a family with immune dysregulation syndrome and severe retinal vasculitis and macular edema.

Methods: Primary retinal pigment epithelial (RPE) cells were transduced with STAT3 wildtype (WT), the retinal disease-associated familial STAT3 GOF variant p.L387R, or another pathogenic STAT3 GOF variant (p.Y360C) linked to immune dysregulation without retinal involvement. Cells were subsequently stimulated with IL-6 and IFN-α. RNA sequencing was performed to analyze gene expression differences, particularly related to cytokines, chemokines, and factors associated with RPE barrier permeability. Additionally, the expression of tight junction proteins involved in the blood-retinal barrier integrity was assessed. The efficacy of JAK inhibitors to modulate hyperactivation of the IL-6 R/JAK/STAT3 pathway was also evaluated.

Results: Compared with WT and STAT3 p.Y360C variant-expressing cells, those expressing STAT3 p.L387R variant produced significantly elevated levels of IL-6, CCL2, and VEGF-A, which are known contributors to vascular leakage in retinal endothelial cells. Treatment with JAK1/2 inhibitors effectively reduced SOCS3 overexpression in STAT3 GOF RPE cells.

Conclusion: The pathogenic STAT3 p.L387R GOF variant enhances inflammatory cytokine production in human primary RPE cells, potentially exacerbating retinal vascular leakage and macular edema. These effects can be mitigated by JAK1/2 inhibition, highlighting a promising therapeutic strategy for retinal inflammation and associated edema.

External ophthalmomyiasis is an acute parasitic infection resulting from the infestation of ocular surface tissues by larvae of the order Diptera. It occurs more frequently in tropical and subtropical regions with inadequate sanitation, particularly among individuals in close contact with livestock. Patients often present with severe ocular irritation, including foreign body sensation, redness, pain, and increased lacrimation; severe cases may develop complications such as keratitis or intraocular involvement. Diagnosis primarily relies on the direct visualization of larvae under slit-lamp microscopy. The cornerstone of treatment involves the mechanical removal of larvae under topical anesthesia, supplemented by local application of antimicrobial and anti-inflammatory agents. This review systematically summarizes current knowledge regarding the epidemiology, clinical features, and management advances, with the aim of enhancing clinical recognition and therapeutic outcomes.

Purpose: To report a boy with IgA vasculitis (IgAV), who suffered two episodes of Posterior Scleritis (PS). This is the first reported case of this association.

Methods: Case report based on medical record review.

Results: A 13-year-old boy with IgAV presented with left eye (LE) pain. Although the eye examination was unremarkable, Magnetic resonance imaging (MRI) revealed PS; appropriate treatment was initiated, resulting in an excellent response. Later, a similar episode occurred in the right eye (RE) accompanied by a violaceus papule on the tip of the nose.

Conclusion: PS may be associated with IgAV in children. MRI was crucial to detect the PS in this case. Nonsteroidal anti-inflammatory drugs (NSAIDs) were effective first-line treatment.

Purpose: To present a case of retinal toxicity following intravitreal clindamycin injection in a patient with toxoplasma retinochoroiditis and to review the relevant literature.

Methods: A single case was evaluated, documented, and described.

Results: A 41-year-old woman with reactivated Toxoplasma retinochoroiditis in her right eye received intravitreal clindamycin (1 mg/0.1 mL) and dexamethasone (0.4 mg/0.1 mL). Regrettably, her visual acuity declined to hand motion one day post-injection. Fundus examination revealed extensive macular necrosis with retinal vascular occlusion, suggestive of retinal infarction. Despite high dose systemic steroid therapy, her condition progressed to macular atrophy and severe vision loss.

Conclusion: Macular infarction is a rare but devastating complication of intravitreal clindamycin injection. This risk should always be considered when intravitreal therapy is planned for the treatment of ocular toxoplasmosis.

Purpose: To report the clinical presentations and outcome of ocular tuberculosis (OTB) in an Egyptian cohort.

Methods: The medical records of 42 consecutive patients with presumed ocular tuberculosis referred to a tertiary referral center in Alexandria, Egypt, were reviewed retrospectively.

Results: Sixty-seven eyes of 42 patients were included in the study. The most common clinical presentation was anterior and intermediate uveitis in 25 eyes (37.3%), followed by anterior uveitis in 14 eyes (20.9%), intermediate uveitis in 11 eyes (16.4%), panuveitis in 10 eyes (14.7%), scleritis and sclerouveitis in 4 eyes (5.8%), and posterior uveitis in 3 eyes (4.5%). Nearly half of the patients, 20 patients (47.6%), were treated with combined ATT and oral corticosteroids; 8 patients (19%) received ATT alone; 6 patients (14.3%) were treated with oral corticosteroids only; and 11 patients (19.1%) were started on systemic immunosuppressants after initiation of ATT. Periocular corticosteroids were required in 14 patients (33.3%) and intravitreal Ozurdex injections in 6 patients (14.3%) to control intraocular inflammation and cystoid macular edema. The most commonly reported ocular complications of tubercular uveitis were posterior synechiae, followed by cystoid macular edema, cataract, and ocular hypertension.

Conclusion: Ocular tuberculosis should be considered in cases of recurrent or treatment-resistant uveitis, even in patients without systemic Tb manifestation and with normal chest imaging. In our cohort, anterior and intermediate uveitis were the most common presentations. Most cases were treated with antituberculous treatment whether alone or combined with oral corticosteroids for optimal disease control.

Purpose: Intermediate uveitis (IU) can occur secondary to systemic autoinflammatory disorders, such as juvenile idiopathic arthritis and multiple sclerosis. In contrast, pars planitis (PP) specifically refers to an idiopathic form of IU, characterized by the absence of any identifiable underlying systemic condition. The frequency of the association between PP and CNS demyelination is unknown in children.

Methods: A retrospective analysis of paediatric PP patients' clinical and brain magnetic resonance imaging (MRI) data was conducted to investigate the coexistence of PP and CNS demyelinating pathologies in children.

Results: The cohort comprised 65 paediatric patients with PP, mean age 13.25 ± 3.1, (range 6-18, median 13) years, 41.5% female, who had at least one brain MRI. The mean follow-up was 4.02 ± 2.76 (range 0.5-11, median 4) years. Demyelinating lesions on MRI were visible in 5/65 (7.7%) patients. None reported neurological symptoms nor had abnormal findings on neurological examination. Three patients who had been undergoing adalimumab (ADA) treatment for a period of between three months and four years had their ADA therapy stopped when a demyelinating lesion was observed on MRI. Additionally, mycophenolate mofetil or methotrexate treatment was maintained as a maintenance therapy. The other two patients had not received any immunomodulatory treatment when demyelinating lesions were identified, and MRI findings were taken into consideration when treatment was planned.

Conclusions: Demyelinating lesions of the CNS can be detected in paediatric PP patients at a rate similar to adults. Clinicians should be aware of the presence of silent demyelination in PP and plan the anti-inflammatory treatment accordingly.