Ocular Immunology and Inflammation最新文献

Purpose: We report a rare case of CMV-associated conjunctival atypical lymphoid hyperplasia (ALH).

Methods: A case report.

Results: A 34-year-old Chinese male with a 2-year history of recurrent bilateral redness, photophobia, and tearing, and no systemic or prior ocular illnesses, presented with severe bilateral conjunctival hyperemia, gelatinous limbal hyperplasia, and corneal opacities. Surgical excision was performed. Histopathology and immunohistochemistry revealed atypical lymphoid hyperplasia with a clonal B-cell population and CMV positivity within the lesional tissue.

Conclusion: This case expands the clinical spectrum of ocular CMV disease and underscores the importance of considering CMV in the differential diagnosis of chronic, atypical conjunctival lesions. The relationship between CMV infection and ALH warrants further investigation. Long-term follow-up is needed to monitor for local recurrence or progression to overt lymphoma.

Purpose: To describe the demographics, clinical characteristics, treatment patterns, and outcomes of pediatric patients with noninfectious posterior and panuveitis at a single center.

Methods: Retrospective cohort study of all eyes with posterior and panuveitis between June 2015 and June 2025 that were identified using ICD codes. Charts were reviewed for demographics, clinical characteristics, disease evolution, sequelae, and treatment. Eyes with less than 3 months of follow-up were excluded.

Results: Between 2015 and 2025, a total of 12 004 patients (16,810 eyes) were seen for any uveitis diagnosis. Of them, 281 children (449 eyes) were referred for a diagnosis of non-infectious uveitis and 106 eyes of 69 patients met inclusion criteria. Bilateral disease occurred in 50.7% of patients. The leading diagnosis was idiopathic uveitis (51.9% of eyes), with a mean follow-up of 42 months. Nearly all eyes experienced at least one inflammatory flare (mean 1.1 per eye). Topical corticosteroids were most used (60.9% of treated eyes). Ocular sequelae were nearly universal (98.1%), and the proportion of patients with vision 20/200 or worse remained stable from baseline to follow-up (39.1% vs 40.6%). Linear mixed-effects modeling identified glaucoma (β×t =  +0.0141 logMAR/month, p < 0.001) and vitreous opacities (β×t =  +0.0096, p = 0.005) as the sequelae most strongly associated with visual decline. Methotrexate was independently associated with a more favorable visual acuity trajectory (β×t =  -0.0071 logMAR/month, p < 0.001).

Conclusions: Pediatric noninfectious posterior and panuveitis is characterized by chronic, bilateral disease with near-universal sequelae. Glaucoma and vitreous opacities were the strongest drivers of visual decline, while methotrexate was associated with visual preservation, supporting its early use in this population.

Purpose: Dupilumab is an injectable human IgG4 monoclonal antibody targeting the IL-4 receptor indicated for moderate to severe atopic dermatitis (AD) refractory to standard topical treatments. We report an association of dupilumab with non-infectious posterior uveitis in a 10-year-old boy.

Methods: Case report.

Results: A 10-year-old boy was referred for specialty eye examination due to bilateral blurry vision, redness, and light sensitivity unresponsive to topical ocular corticosteroids in the setting of using dupilumab for severe AD. There was iritis and vitreitis and numerous yellow-white moderate-sized retinochoroidal lesions in both eyes, with evidence of retinal vasculitis in one eye. Optical coherence tomography showed sublesional choroidal swelling with sub-retinal pigment epithelial deposits, full thickness retinal hyperreflectivity, and overlying vitreous cells. Fluorescein angiography revealed early blockage and late staining of lesions. Indocyanine green angiography showed hypofluorescent lesions throughout the course. An extensive immunological and infectious workup was negative. Dupilumab was stopped with some improvement noted. He was started on oral corticosteroids with additional improvement and rapidly transitioned to steroid-sparing therapy with mycophenolate, methotrexate and adalimumab. New retinal hemorrhages and inflammatory signs resolved after starting adalimumab. Visual acuity was maintained at 20/20. He was diagnosed with relentless placoid chorioretinopathy - possible associated with dupilumab use, which was permanently discontinued.

Conclusion: Relentless placoid chorioretinopathy is a rare sight-threatening posterior uveitis that is ordinarily classified as undifferentiated but, in this case, could be an immunologic reaction to dupilumab. The immunopathogenic mechanism is presumably related to dupilumab-mediated Th2 IL-4/IL-13 dual blockade which polarizes Th17 (IL-23/IL-17) responses.

Purpose: To analyze the tear fluid proteome of non-infectious acute anterior uveitis to identify objective markers of inflammation and further dissect the underlying disease pathology.

Methods: Patients from the Uveitis arm of the German Spondyloarthritis Inception cohort with available tear fluid samples and consecutive patients attending the Ophthalmology Department were included. In total, 47 patients with unilateral, non-infectious acute anterior uveitis, including 23 with follow-up samples during non-inflamed state, and 23 healthy controls were enrolled. Tear fluid was collected using Schirmer strips from both eyes during unilateral inflammation and ≥5 months after uveitis resolution from the initially inflamed eye, and from the left eye of healthy individuals. Proteomic analysis was performed by mass spectrometry in data-independent acquisition mode.

Results: A total of 1,994 proteins were consistently identified in the tear fluid. Of these, 24 proteins were significantly differently expressed in the eye with active uveitis compared to the non-inflamed fellow eye: the most strongly upregulated proteins were protein S100-P, villin-like protein, and glutamine synthetase, while the most downregulated proteins were protein S100-A7, immunoglobulin kappa joining 3, and prostaglandin D2 synthase. The latter was also downregulated in active uveitis compared to follow-up and healthy controls. Compared to the post-inflammatory samples, active uveitis showed 201 differentially expressed proteins, including upregulation of proteins related to unfolded protein binding and downregulation of proteins involved in metabolic processes and energy-related pathways.

Conclusion: Uveitis alters the tear fluid proteome, indicating the potential of identifying biomarkers useful for diagnostics and monitoring the course of inflammation.

Purpose: To investigate the correlation between viral load, interleukin-8 (IL-8) levels and clinical outcomes during antiviral therapy in patients with acute retinal necrosis (ARN).

Methods: Before intravitreal injections of ganciclovir, aqueous humor samples were collected from 43 ARN patients (53 eyes). Viral load was quantified using polymerase chain reaction (PCR) and IL-8 concentrations were analyzed using enzyme-linked immunosorbent assay (ELISA). Relevant medical records and clinical characteristics were collected for analysis.

Results: Varicella zoster virus (VZV) was detected in 49 eyes (92.5%). No significant difference in Best-corrected visual acuity (BCVA) was found between baseline and final follow-up (p = 0.43). In VZV-induced ARN eyes, those with high initial viral loads (≥5.0 × 10⁶ copies/ml) had significantly worse baseline and final BCVA than those with low viral load (p₁ < 0.01, p₂ < 0.01). Worse final BCVA correlated positively with both higher baseline VZV DNA loads (r = 0.14, p < 0.01) and elevated IL-8 levels (r = 0.26, p < 0.01). After treatment, viral load and IL-8 levels showed a plateau phase and a subsequent decrease. The viral load plateau lasted two weeks, while the IL-8 plateau lasted only one week. Viral load changes were positively correlated with IL-8 changes after antiviral therapy (r = 0.33, p < 0.01).

Conclusion: Monitoring aqueous viral load and IL-8 levels may serve as a potential indicator for assessing the efficacy of antiviral treatment. Notably, IL-8 demonstrates greater sensitivity in reflecting the treatment response.

Uveitis and scleritis are well-recognized extraintestinal manifestations of inflammatory bowel disease (IBD). Although ocular involvement typically follows IBD diagnosis, a meaningful subset of patients presents to ophthalmologists before intestinal disease is recognized, sometimes years earlier. Despite this, no standardized ophthalmologic screening protocols exist to guide early detection. We synthesized cohort studies, meta-analyses, and Mendelian randomization evidence on the ocular-intestinal temporal relationship in IBD. Patients with uveitis or scleritis have approximately double the risk of a subsequent IBD diagnosis (adjusted HR 1.44-2.25), with median diagnostic intervals exceeding two years and often longer in pediatric populations (>5 years). Mendelian randomization studies provide genetic evidence supporting a causal effect of IBD on uveitis. In a large pediatric cohort (n = 2,555), ocular manifestations preceded IBD in approximately 20% of cases. Uveitis occurs more frequently in Crohn's disease than in ulcerative colitis, and no ophthalmology guideline provides actionable screening criteria for IBD. We propose a tiered, risk-stratified framework to identify undiagnosed IBD in ophthalmology settings: (Tier 1) universal gastrointestinal symptom screening for non-infectious or recurrent uveitis and all scleritis; (Tier 2) targeted laboratory evaluation, including fecal calprotectin in high-risk patients; and (Tier 3) low-threshold gastroenterology referral for positive screens or persistent clinical concern. Lower referral thresholds are appropriate in pediatric populations. This framework is proposed to complement clinical judgment and requires prospective validation before adoption as standard practice. By recognizing ocular inflammation as an early systemic signal, ophthalmologists are uniquely positioned to reduce diagnostic delay and improve interdisciplinary care in IBD.

Purpose: This study aims to demonstrate the efficacy of adalimumab (ADA) in reducing overall treatment burden in a cohort of patients with idiopathic multifocal choroiditis (MFC)/punctate inner choroidopathy (PIC).

Methods: This is a retrospective case series of eyes classified as having idiopathic MFC/PIC using standard multi-modal imaging, including color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. LogMAR best-corrected visual acuity (BCVA), doses of prednisone and other immunomodulatory therapies (IMT), injections of corticosteroids or anti-vascular endothelial growth factor (anti-VEGF), and breakthrough flares were collected at baseline (initiation of ADA), 12 months from baseline, and last follow-up.

Results: Twenty-five patients (21 females, 41 eyes) were included. Mean follow-up time was 51.4 ± 35.2 months (range 9.2-126.6). Mean LogMAR BCVA was 0.35 ± 0.48 at baseline and 0.34 ± 0.55 at last follow-up (p > 0.5). Mean prednisone dosage decreased significantly from 15.76 ± 18.69 mg/day at baseline to 0.23 ± 1.1 mg/day at the last follow-up (p < 0.0001). Thirty eyes received steroid or anti-VEGF injections at baseline; this decreased to one at the last follow-up (p < 0.0001). Similarly, eight patients received other IMT at baseline, but only one continued to receive supplemental IMT at the last follow-up (p < 0.05) at a decreased dosage. Six patients experienced disease flare-up within the first 12 months of treatment, and three patients flared between 12 months and last follow-up.

Conclusions: Adalimumab therapy demonstrated a significant steroid-sparing effect in addition to vision preservation and reduction in both anti-VEGF injections and IMT.

Purpose: To evaluate the diagnostic yield, clinical utility and cost of common screening investigations in patients presenting with acute anterior uveitis (AAU).

Methods: Subjects with acute anterior uveitis were retrospectively identified from the Inflammatory Eye Disease Registry at Greenlane Clinical Centre, Auckland, New Zealand. Subjects were excluded if there was a pre-existing systemic disease known to cause AAU. Demographics, clinical presentation, diagnosis, human leukocyte antigen (HLA) B27, syphilis serology, serum angiotensin converting enzyme (ACE), chest x-ray and C-reactive protein (CRP) were assessed.

Results: 1040 subjects were included in the study. Median age was 43.9 years with 57.1% male. Systemic disease was documented in 487 subjects (46.8%). Predictors of systemic disease on multivariate analysis included younger age (OR 0.987 p = 0.006), hypopyon (OR 4.960 p = 0.015) and high CRP (OR 1.525 p = 0.009). High intraocular pressure at presentation (≥24 mmHg) was associated with a lower risk of systemic disease (OR 0.229 p < 0.001) as was bilateral presentation (OR 0.417 p < 0.001). Cost of screening per true positive identified was $178.37 for HLA-B27, $2,144.81 for syphilis serology, $4,470.93 for serum ACE, and $5,389.17 for chest x-ray.

Conclusions: The cost of screening in patients with AAU varied significantly between tests, with a high yield observed from HLA-B27 and syphilis and a low yield from sarcoid and chest x-ray. Costs can be optimized by selecting higher-risk patients via history and examination. Any AAU screening protocol must consider the diagnostic utility of an individual test and the cost of a missed systemic diagnosis.

Purpose: We evaluated the long-term safety and efficacy of high-dosage infliximab and biosimilars (IFX+) in recalcitrant, non-infectious inflammatory retinal vasculitis (RV) after antimetabolite and adalimumab failure.

Methods: This retrospective study included patients from the University of Illinois at Chicago Uveitis Service (2014-2024) who transitioned to IFX+ after prior treatment failure. Patients were categorized into low-dosage (LD, ≤5 mg/kg/Q4W, n = 14), medium-dosage (MD, 5.5-9.5 mg/kg/Q4W, n = 8), and high-dosage (HD, ≥10 mg/kg/Q4W, n = 9) groups. Efficacy was defined as ≥ 1 zone fluorescein angiographic (FA) improvement, prednisone reduction to < 10 mg/day with no flares, or both, at 6, 12, and 24 months, and last follow-up. Secondary outcomes included visual acuity (VA) and central macular thickness changes.

Results: At 12 months, efficacy was achieved by 57.1%, 87.5%, and 88.9% of LD, MD, and HD IFX+ patients, increasing to 83.3%, 75.0%, and 100% by last visits. FA improvement rate was 60.0% (LD), 50.0% (MD), and 87.5% (HD) at 12 months, increasing to 71.4%, 60.0%, and 100% at last visits. VA significantly improved in HD by 12 months (p = 0.03) and MD by 24 months (p = 0.02). LD and MD groups required dosage increases to sustain inflammation control. By 24 months, no significant dosage differences between groups existed. No adverse events were reported in the HD group.

Conclusion: In this retrospective study, medium- and high-dosage IFX+ achieved better inflammation control and visual outcomes versus low-dosage IFX+, with no additional safety concerns, in treating recalcitrant non-infectious inflammatory RV. Early initiation at greater dosages may optimize IFX response, reduce treatment duration, and improve health-related quality of life.

Purpose: To determine the long-term association of systemic autoimmune disease, infection, and vitreoretinal lymphoma in patients initially diagnosed with undifferentiated uveitis, stratified by anatomical location.

Methods: Retrospective cohort study using a multicenter electronic health records database. We identified patients ≥18 years with the index diagnosis of undifferentiated uveitis. We excluded patients if they had an autoimmune, infectious, adverse drug reaction, or positive autoimmune serologic markers at baseline. We stratified patients by time (6 months, 5 years, and 15 years) and anatomical location (anterior, intermediate, and posterior/panuveitis). We estimated survival probabilities and reported cumulative incidence using a time-to-first event analysis.

Results: We analyzed 39 703 patients with undifferentiated uveitis at baseline. Mean age was 51 years. The cohort was predominantly female (21,894, 57%), non-Hispanic (27,915, 72%), and White (20,467, 53%). Systemic autoimmune disease demonstrated the highest cumulative incidence at 15 years (25.93%), with infectious disease being 11.61% and lymphoma approximating between 0.12% and 2.78%. Inflammatory spondyloarthropathy (SpA) showed the greatest systemic diagnosis outcome (8.62%) while herpes viruses were the predominate infectious etiologic diagnosis (8.02%). Etiologies varied by anatomy with inflammatory SpA demonstrating the greatest cumulative incidence among anterior uveitis (34.14%), multiple sclerosis displaying a high cumulative incidence among intermediate uveitis (7.23%), and lymphoma concentrating in posterior/panuveitis (0.35%-5.22%).

Conclusion: Undifferentiated uveitis potentially carries a risk of association with systemic autoimmune disease compared to other etiologies over time. Although less frequent, infectious etiologies remain a significant presence in later diagnoses. Longitudinal monitoring is critical for the correct etiological diagnosis of uveitis.