Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

BACKGROUND: Type I interferons (IFNs) promote the expansion of subsets of CD1c+ conventional dendritic cells (CD1c+ DCs), but the molecular basis of CD1c+ DCs involvement in conditions not associated without elevated type I IFNs remains unclear. METHODS: We analyzed CD1c+ DCs from two cohorts of non-infectious uveitis patients and healthy donors using RNA-sequencing followed by high-dimensional flow cytometry to characterize the CD1c+ DC populations. RESULTS: We report that the CD1c+ DCs pool from patients with non-infectious uveitis is skewed toward a gene module with the chemokine receptor CX3CR1 as the key hub gene. We confirmed these results in an independent case-control cohort and show that the disease-associated gene module is not mediated by type I IFNs. An analysis of peripheral blood using flow cytometry revealed that CX3CR1+ DC3s were diminished, whereas CX3CR1- DC3s were not. Stimulated CX3CR1+ DC3s secrete high levels of inflammatory cytokines, including TNF-alpha, and CX3CR1+ DC3 like cells can be detected in inflamed eyes of patients. CONCLUSIONS: These results show that CX3CR1+ DC3s are implicated in non-infectious uveitis and can secrete proinflammatory mediators implicated in its pathophysiology. FUNDING: The presented work is supported by UitZicht (project number #2014-4, #2019-10, and #2021-4). The funders had no role in the design, execution, interpretation, or writing of the study

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment

An Ocular Protein Triad Can Classify Four Complex Retinal Diseases

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions

Intraocular Inflammation Associated with Ocular Toxoplasmosis: Relationships at Initial Examination

PURPOSE: To describe characteristics of intraocular inflammation in eyes with active ocular toxoplasmosis and to identify relationships between signs of inflammation, complications (including elevated intraocular pressure [IOP]), other disease features, and host characteristics.DESIGN: Multicenter, retrospective, cross-sectional study.METHODS: We reviewed the medical records of 210 patients with toxoplasmic retinochoroiditis at seven in ternational sites (North America, South America, and Europe) for information from the first examination at each site during which patients had active retinal lesions. Signs of inflammation included anterior chamber (AC) cells and flare and vitreous humor cells and haze. Retinal lesion characteristics included size (1 DA) and presence or absence of macular involvement.RESULTS: AC cells and flare were related to vitreous inflammatory reactions (P <= .041). One or more signs of increased inflammation were related to the following factors: older patient age, larger retinal lesions, and extramacular location. in 30% of involved eyes, there was evidence of elevated IOP (despite use of glaucoma medications by some patients); other complications were uncommon. IOP of more than 21 mm Hg was associated with both increased AC cells and elevated flare (both P <= .001) and with macular involvement (P = .009). Inflammation seemed to be more severe among patients in Brazil than among those at other sites.CONCLUSIONS: There is substantial variation between patients in the severity of intraocular inflammation associated with ocular toxoplasmosis, attributable to multiple host and disease-related factors. Results suggest that disease characteristics also vary in different areas of the world. Elevated IOP at initial examination reflects the severity of inflammation. (Am J Ophthalmol 2008;146:856-865. (C) 2008 by Elsevier Inc. All rights reserved.)RESEARCH TO PREVENT BLINDNESS INC, NEW YORK, NEW YORKJULES Stein Eye InstituteSkirball Foundation, New York, New YorkHeed Foundation, Chicago, IllinoisEmily Plumb Estate and TrustConsultores Oftalmol, RA-1018 Buenos Aires, DF, ArgentinaUniv Calif Los Angeles, David Geffen Sch Med, Ocular Inflammatory Dis Ctr, Jules Stein Eye Inst, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USAKings Coll London, London WC2R 2LS, EnglandUniv Med Ctr, FC Donders Inst Ophthalmol, Utrecht, NetherlandsUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniv Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USAMed Univ Vienna, Univ Klin Augenheikunde & Optometrie, Vienna, AustriaMalayan Eye Inst, Yerevan, ArmeniaUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc