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.