Ocular Immunology and Inflammation最新文献

Dry eye disease (DED), a multifactorial disorder characterized by tear film instability and ocular surface inflammation, remains a therapeutic challenge due to its complex immunopathogenesis. Emerging evidence highlights dendritic cells (DCs), including conventional (cDCs) and plasmacytoid subsets (pDCs), as pivotal mediators bridging innate and adaptive immune responses in DED. This review delineates the mechanisms by which DCs drive DED progression. Hyperosmolar stress, apoptotic debris, and goblet cell dysfunction activate DCs, promoting their migration to draining lymph nodes and subsequent priming of Th1/Th17 cells, which perpetuate lacrimal gland inflammation and ocular surface damage. Functional alterations in DCs that exacerbate neural-immune crosstalk include upregulated TLR7/9, STING, and S100A8/A9 pathways, and enhanced pro-inflammatory cytokine production including IL-12, IFN-I, and IL-23. Clinically, in vivo confocal microscopy reveals elevated corneal DCs density and activation, which correlate with symptom severity, tear break-up time, and corneal nerve abnormalities, underscoring their potential as diagnostic and prognostic biomarkers. Therapeutic strategies targeting DCs include reducing DCs density and activation (e.g. netrin-1, mesenchymal stem cell-derived extracellular vesicles), modulating inflammatory cytokine production (e.g. thrombospondin-1, mesenchymal stem cell, and butyrate), and regulating DCs-T cells interactions (e.g. neurokinin-1 antagonists, CD40/CD40L blockade), which offer novel avenues for immune regulation.

Purpose: This study aimed to investigate anterior scleral stromal thickness (AST) in patients with rheumatoid arthritis (RA) and primary Sjögren's Syndrome (SjS) compared with healthy controls and to explore its relationship with disease duration.

Methods: The study included 156 participants: 58 with RA, 42 with SjS and 56 healthy controls. The majority of participants were women (n = 130), with a mean age of 51.1 ± 9.38 years. All patients were receiving immunosuppressive therapy and had no history of scleritis. AST and conjunctiva-tenon-episcleral complex thickness (CTEC) were measured using anterior segment OCT at distances of 0, 1, 2 and 3 mm from the scleral spur in the medial-inferior-lateral-superior quadrants. Statistical analyses, including group comparisons and correlation analyses, were performed to assess intergroup differences and associations with disease duration.

Results: The proportion of women was significantly higher and the disease duration was significantly shorter in the SjS group. Compared with controls, the RA group showed significantly thinner medial CTEC at 1, 2, and 3 mm from the scleral spur, whereas inferior AST at the scleral spur was thicker. No significant differences in AST or CTEC parameters were observed in the SjS group relative to controls.

Discussion: RA is associated with localized alterations in anterior scleral morphology, while SjS does not appear to significantly affect these parameters. These findings may reflect the impact of timely diagnosisand effective immunosuppressive therapy in limiting ocular tissue involvement. However, the absence of a standardized anatomical reference point for scleral thickness measurements complicates direct comparison among scientific studies.

Purpose: Tubulointerstitial nephritis and uveitis (TINU) syndrome is traditionally treated with corticosteroids followed by antimetabolites. The efficacy of early tumor necrosis factor-α (TNF) inhibitor therapy in TINU has not been sufficiently assessed. This case series describes the ocular and renal outcomes of treating TINU with TNF inhibitors (TNFi) and antimetabolites.

Methods: Retrospective data was collected on medication use and outcomes in nine pediatric TINU patients. Patients were split based on corticosteroid-sparing therapy: Group A only used antimetabolites and Group B used TNFi. Groups were assessed for corticosteroid sparing efficacy, renal and ocular quiescence, and medication adverse effects.

Results: There were two Group A and seven Group B patients. Five Group B patients previously failed antimetabolite monotherapy. In Group A, median time from corticosteroid-sparing therapy initiation to prednisone cessation was 26.5 weeks, during which mean peak body mass index (BMI) increase was 1.65 kg/m². In Group B, median corticosteroid sparing time was 28 weeks and mean BMI increase was 4.16 kg/m². After removing time on antimetabolite monotherapy, median corticosteroid sparing time was 6 weeks and mean BMI increase was 2.03 kg/m². Five patients taking antimetabolites and one taking TNFi had uveitis relapses. No renal relapses were reported. Only mycophenolate mofetil was associated with symptomatic adverse effects.

Conclusions: TNFi controlled ocular and renal inflammation in TINU. Furthermore, some patients fail antimetabolite therapy and experience side effects of prolonged corticosteroid therapy. We recommend early and even first-line usage of TNFi as corticosteroid-sparing therapy with or without antimetabolites.

Purpose: To determine the demographic profile, clinical features, investigative results, management, lesion-specific outcomes, complications and follow-up of diagnosed sarcoid posterior uveitis (SPU) cases, presenting at a single tertiary care hospital.

Methods: A retrospective observational study was carried out. Details of all SPU cases were extracted from electronic medical records of a tertiary care center in India.

Results: Seventy-two eyes (of 43 patients) were included, of which 31 were bilateral SPU. Mean age of patients was 41.7 ± 13.0 years and 55.8% were females. The most common lesion noted was choroidal granulomas (62%). The mean presenting BCVA was-0.35 ± 0.5 logMAR which varied across lesion subtypes. Steroid was the mainstay of treatment and 90% cases were also started on immunosuppressives (IMT). Fifty-two eyes were followed up for 6 months. BCVA was stable in 75%, improved in 15.4% & declined in 9.6%. Lesion-specific visual prognosis and clinical response to treatment were analysed. Clinical response to treatment and visual acuity outcomes were noted to be better in retinal vasculitis and choroidal granulomas as opposed to eyes with multifocal choroiditis.

Conclusion: Sarcoid posterior uveitis is associated with a significant visual morbidity. Early identification of cause and manifestations are imperative. Timely treatment with steroids and IMT can cause resolution of uveitis and improvement in vision. The visual prognosis and response to treatment depend on lesion subtype of SPU.

Introduction: Birdshot chorioretinopathy (BSCR) is a chronic posterior uveitis. In some cases, hyperreflective material between the retinal pigment epithelium (RPE) and Bruch's membrane is noted on optical coherence tomography (OCT), the so-called double-layer sign. This study describes the clinical features associated with the double-layer sign on OCT in BSCR.

Methods: In retrospective, observational study of patients with BSCR, charts and OCT images of consecutive patients were reviewed and the presence of the double-layer sign on OCT was noted. Clinical features associated with the double-layer sign were analyzed.

Results: Forty-nine patients with HLA-A29+ BSCR were retrospectively reviewed and 15 eyes (15%) of 9 patients (18%) demonstrated the presence of the double-layer sign on OCT. The presence of CNV corresponding to the double-layer sign on OCT was confirmed in eyes that had additional imaging (11 out of 15 eyes; 73%). Intra- or subretinal exudation was present at some point during follow-up in 5/15 eyes (33%), and 3/15 eyes received treatment with intravitreal bevacizumab (20%).

Conclusions: Birdshot chorioretinopathy can develop a double-layer sign on OCT often harboring a non-exudative or minimally active choroidal neovascularization. This sign in patients with BSCR might indicate chronic inflammation involving the posterior pole.

Purpose: To describe the management patterns and outcomes among patients with incisional glaucoma surgery-associated endophthalmitis.

Methods: Retrospective review of all patients treated for endophthalmitis following standalone incisional glaucoma surgery (trabeculectomy and glaucoma drainage device (GDD) implants at a single institution). Data were recorded on clinical course, microbiological findings, management, and treatment outcomes.

Results: A total of 101 eyes with incisional glaucoma surgery-related endophthalmitis were identified, of which 66% (N = 67/101) were trabeculectomy related. The mean (SD) time from surgery to endophthalmitis presentation was 4.9 (6.3) years for trabeculectomies and 3.6 (4.5) years for GDD implant surgery. Most (N = 98/101, 97%) eyes underwent initial treatment with intravitreal antibiotics alone. Of the 98 eyes undergoing initial treatment with intravitreal antibiotics, 14% (N = 14/98) underwent a repeat injection of antibiotics, and 16% (N = 16/98) underwent a subsequent PPV after initial treatment. A higher proportion of eyes with GDD-related endophthalmitis underwent repeat injection with intravitreal antibiotics compared to eyes with trabeculectomy-related endophthalmitis (23.5% vs 9.0%, p = 0.045). The overall culture-positive rate was 30% (N = 26/85), with gram-positive microorganisms being more common. The mean presenting logMAR VA was 2.36 (Snellen equivalent 20/4600). Mean logMAR VA at last follow-up was 1.90 (Snellen equivalent 20/1600), with a mean (SD) follow-up duration of 2.6 (2.8) years.

Conclusions: Visual outcomes following incisional glaucoma surgery-associated endophthalmitis remain guarded. Most patients were managed with intravitreal antibiotics alone. Eyes with GDD-related endophthalmitis may be more likely to undergo repeat injection of intravitreal antibiotics.

Purpose: To compare the clinical effectiveness and safety of subcutaneous adalimumab (SCA) versus intravitreal adalimumab (IVA) in treating active non-infectious uveitis (NIU).

Methods: This single-center, phase 2 non-inferiority randomized controlled trial included patients with active NIU assigned to receive either SCA (80 mg loading dose, then 40 mg every 2 weeks) or IVA (1.5 mg at baseline, then every 4 weeks). Follow-ups occurred weekly for the first 2 weeks, then every 4 weeks until 26 weeks. Primary outcomes were changes in anterior chamber cell (AC) and vitreous haze (VH) grades at 26 weeks (non-inferiority margin: 0.5). Secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), fluorescein angiography (FA) score, and oral prednisone dose.

Results: A total of 23 patients (43 eyes) were randomized into the SCA (n = 12) or IVA (n = 11) treatment group. IVA was found to be non-inferior to SCA. The upper limit of the 90% confidence interval (CI) for the difference in AC grade change (-0.33 [-0.79 to 0.38], p = 0.440) and VH grade change (-0.34 [-1.15 to 0.47], p = 0.490) remained below the noninferiority margin of + 0.5 grade. No significant differences were found between the two treatment groups for secondary outcomes, including changes in BCVA (p = 0.594), CRT (p = 0.607), FA score (p = 0.318), and oral prednisone dose (p = 0.881). No serious systemic or ocular adverse events (AE) were observed. SCA resulted in a higher number of non-serious systemic AE (21) compared to IVA (5).

Conclusions: IVA was non-inferior to SCA in treating active NIU and resulted in fewer systemic adverse events.

In response to recent comments on our meta-analysis, we reaffirm that smoking is a major modifiable risk factor for uveitis, with consistent evidence demonstrating increased odds of disease across multiple anatomic subtypes. Biological plausibility is supported by mechanisms such as oxidative stress, endothelial dysfunction, and cytokine activation. Smoking also affects treatment response: current smokers with immune-mediated diseases such as psoriasis, Crohn's disease, and rheumatoid arthritis show reduced likelihood of achieving remission or near-complete clearance after biologic therapy. Tobacco use contributes to systemic organ damage, including cardiovascular, pulmonary, and ocular complications such as macular edema. Heterogeneity in exposure assessment and limited e-cigarette data highlight the need for further research. Nevertheless, clinicians should actively counsel patients to stop smoking or vaping. Reducing modifiable risk factors may improve treatment efficacy, lower inflammation, and prevent recurrence. Ophthalmologists play a key role in prevention and optimizing outcomes in uveitis.

Purpose: This study aims to investigate the risk of developing ocular adverse events, including uveitis, with bisphosphonate use and to analyze the factors that may lead to higher risks of developing the symptoms.

Materials & methods: A systematic search was conducted across multiple databases, including PubMed, Web of Science, Airiti Library, and Cochrane Library, to identify randomized controlled trials and their post-hoc analyses on bisphosphonate use published before February 2025 that reported ocular adverse events as the primary outcome or in safety analysis. A random-effects meta-analysis was utilized to evaluate the results. Additionally, the impact of different routes of administration and different generations of bisphosphonates on the risk of ocular adverse events were analyzed. The effect estimate was presented with risk ratio.

Results: Sixteen studies with a total of 15 062 patients were included in this systematic review. Bisphosphonate use resulted in a significantly higher risk ratio of developing overall ocular adverse events (RR = 1.42, 95% CI = [1.13, 1.80]) and uveitis (RR = 5.94, 95% CI = [1.56, 22.59]) compared to placebo. The overall incidence rate of bisphosphonate-associated ocular adverse events was 2.70%. Among studies specifically reporting uveitis, the incidence rate of uveitis was 1.12%. Additionally, the risk of developing these adverse events was significantly higher within 3 days following intravenous bisphosphonate administration (RR = 3.11, 95% CI = [1.61, 6.00]).

Conclusions: Bisphosphonate use is associated with a significantly higher risk of developing ocular adverse events, including uveitis. The first three days following intravenous bisphosphonate administration are associated with an elevated risk of developing ocular adverse events.

Purpose: The more widely known ocular toxicity of Mirvetuximab soravtansine-gynx (MIRV) is keratopathy. Clinical trial data provides little detail on the lesser known toxicity of anterior uveitis from MIRV. We discuss the potential mechanism for this toxicity and provide suggested adjustments to current clinical practice for patients on this drug.

Methods: This retrospective case series, single center study included 42 consecutive patients treated with MIRV at Memorial Sloan Kettering Cancer Center for High-grade serous ovarian cancer and examined in our ophthalmology department between March 1, 2024 - July 15, 2025.

Results: Seventeen of forty-two (40%) patients (median age of 69 years) developed keratitis, and three (7.1%) patients, developed grade 1+ bilateral non-granulomatous anterior uveitis on treatment with MIRV. Uveitis was diagnosed after a median of 12 cycles (range 9-14).

Conclusion: Although a small cohort, our findings suggest that MIRV-induced anterior uveitis is more common than initially thought. Reassuringly, all cases observed have been mild and reversible with topical steroid drops and most patients were able to continue on MIRV (lifesaving) treatment.