Purpose To analyse intraocular cytokine levels and prevalence of intraocular antiretinal antibodies (ARAs) in patients with retinitis pigmentosa (RP), age‐related macular degeneration (AMD), glaucoma and cataract, and correlate the results to clinical manifestations. Methods We collected intraocular fluid samples from patients with RP (n = 25), AMD (n = 12), glaucoma (n = 28) and cataract (n = 22), and serum samples paired with the intraocular fluids from patients with RP (N = 7) and cataract (n = 10). Interleukin (IL)‐1β, IL‐1ra, IL‐2, IL‐6, IL‐6rα, IL‐7, IL‐8, IL‐10, IL‐17A, IL‐23, thymus‐ and activation‐regulated chemokine (TARC), monocyte chemoattractant protein‐1 (MCP‐1), tumour necrosis factor‐alpha (TNF‐α), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) were measured using a multiplex assay. Antiretinal antibodies (ARA) detection was performed by indirect immunofluorescence. Results Increasing age was associated with increasing levels of IL‐6, IL‐8, TNF‐α and VEGF. All patient groups exhibited distinct profiles of intraocular cytokines. Intraocular levels of IL‐8 were highest in patients with AMD and glaucoma. Cataract patients exhibited high intraocular levels of IL‐23. Intraocular levels of IL‐2, IL‐6, MCP‐1 and PlGF in RP patients exceeded the levels of serum, indicating intraocular production. Intraocular ARAs were found in only one patient with AMD. Conclusion Increased levels of inflammatory cytokines in intraocular fluid of patients with originally noninflammatory ocular diseases show that intraocular inflammation is involved in their pathogenesis of these entities. Moreover, we show that increasing age is associated with increasing levels of intraocular cytokines and conclude that future studies on intraocular mediators should be corrected for age of patients.

IMPORTANCE New and improved diagnostic tests for sarcoidosis-associated uveitis are needed because the currently available laboratory diagnostic biomarkers (eg, lysozyme and angiotensin-converting enzyme [ACE]) are lacking in high sensitivity and specificity.OBJECTIVE To compare the value of soluble interleukin 2 receptor (sIL-2R) with ACE as diagnostic biomarkers of sarcoidosis in patients with uveitis.

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PurposeAlthough multiple serum antiretinal autoantibodies (ARAs) have been reported in patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy ((n)pAIR), not all retinal antigens involved in (n)pAIR are specified. This study aims to serologically identify patients with presumed (n)pAIR through determination of both known and unknown ARAs by autoantibody profiling.MethodsAn antigen suspension bead array using 188 different antigens representing 97 ocular proteins was performed to detect ARAs in serum samples of patients with presumed (n)pAIR (n = 24), uveitis (n = 151) and cataract (n = 21). Logistic regressions were used to estimate the associations between ocular antigens and diagnosis. Validation of interphotoreceptor matrix proteoglycan 2 (IMPG2) and recoverin antigens was performed by immunohistochemistry and immunoblot, respectively.ResultsSamples of patients with presumed (n)pAIR exhibited a broad spectrum of ARAs. We identified retinal antigens that have already been described previously (e.g. recoverin), but also identified novel ARA targets. Most ARAs were not specific for (n)pAIR since their presence was also observed in patients with cataract or uveitis. High titers of autoantibodies directed against photoreceptor-specific nuclear receptor and retinol-binding protein 3 were more common in patients with presumed (n)pAIR compared to uveitis (p = 0.015 and p = 0.018, respectively). The presence of all other ARAs did not significantly differ between groups. In patients with presumed (n)pAIR, anti-recoverin autoantibodies were the most prevalent ARAs. Validation of bead array results by immunohistochemistry (anti-IMPG2) and immunoblot (anti-recoverin) showed concordant results in (n)pAIR patients.ConclusionsPatients with (n)pAIR are characterized by the presence of a broad spectrum of ARAs. The diagnosis of (n)pAIR cannot be based on the mere presence of serum ARAs, as these are also commonly present in uveitis as well as in age-related cataract patients.

Purpose Primary vitreoretinal lymphoma [(P)VRL]) is a rare malignancy of the eye localized in the retina, vitreous or choroid. Here, we aim to determine the value of the combination of innovative diagnostic methods for accurate differentiation between (P)VRL and non‐(P)VRL in patients with suspect uveitis or vitritis. Methods Multicolour flow cytometric immunophenotyping of cells in the vitreous samples was performed using the EuroFlow small sample tube. Additionally, cytokines/chemokines and growth factors were measured in the vitreous specimens using a multiplex immunoassay. Data were evaluated in predefined clinical subgroups using omniviz unsupervised Pearson's correlation visualization and unsupervised heatmap analysis. Results A total of 53 patients were prospectively included in the period 2012–2015. In the (P)VRL subgroup (n = 10), nine cases showed aberrant surface membrane immunoglobulin (SmIg) light chain expression. In the non‐(P)VRL group (n = 43) clearly skewed SmIg light chain expression was observed in two multiple sclerosis‐related uveitis cases, but not in other uveitis types. Soluble mediator measurement revealed high interleukin (IL)‐10/IL‐6 ratios, and high IL‐1RA levels in 9/10 (P)VRL cases, but not in any non‐(P)VRL case. Further correlation and heatmap analysis revealed a minimal signature of cellular parameters (CD19+ B cells, aberrant SmIg light chain expression) and cytokine parameters (IL‐10/IL‐6 ratio >1, high IL‐10, high IL‐1 RA, high monocyte chemotactic protein‐1, high macrophage inflammatory protein‐1β) to reliably distinguish (P)VRL from non‐(P)VRL. Conclusion Here, we show the power of a combined cellular and proteomics strategy for detecting (P)VRL in vitreous specimens, especially in cases with minor cellular (P)VRL infiltrates.

BackgroundRetinal detachment is more common among uveitis patients than in the general population. Here, we aimed to assess the prevalence of rhegmatogenous retinal detachment (RRD) in a uveitis population.MethodsWe retrospectively studied 851 uveitis patients, recording characteristics such as uveitis duration, anatomical location, and cause; RRD occurrence; proliferative vitreoretinopathy (PVR) at presentation; surgical approach; reattachment rate; and initial and final visual acuity (VA).ResultsRRD occurred in 26 patients (3.1%; 29 affected eyes) and was significantly associated with posterior uveitis (p < 0.001), infectious uveitis (p < 0.001), and male gender (p = 0.012). Among cases of infectious uveitis, cytomegalovirus and varicella zoster virus were most commonly associated with RRD development. RRD in non-infectious uveitis was not found to be associated with any specific uveitis entity. The rate of single-operation reattachment was 48%, and the rate of final reattachment was 83%. Mean final VA was 20/125, with 41% of eyes ultimately having a VA of less than 20/200.ConclusionUveitis is a risk factor for RRD development, which carries a poor prognosis.

Uveitis and scleritis of autoimmune origin were observed in 5% of the total series. The term autoimmune uveitis should not be used as a synonym for intraocular inflammation of noninfectious origin.

We hypothesize that nivolumab, an immune checkpoint inhibitor, can provoke paraneoplastic acute exudative polymorphous vitelliform maculopathy by means of a tumoral immune reaction with cross-reaction against the retinal pigment epithelium.