Relapse in ocular tuberculosis: relapse rate, risk factors and clinical management in a non-endemic country.

AIMS: To assess the risk of uveitis relapse in ocular tuberculosis (OTB) following clinical inactivity, to analyse clinical factors associated with relapses and to describe the management strategies for relapses. METHODS: A retrospective study was conducted on a 10-year patient registry of patients with OTB diagnosed at Erasmus MC in Rotterdam, The Netherlands. Time-to-relapse of uveitis was evaluated with Kaplan-Meier curve and risk factors for relapses were analysed. RESULTS: 93 OTB cases were identified, of which 75 patients achieved clinical inactivity following treatment. The median time to achieve uveitis inactivity was 3.97 months. During a median follow-up of 20.7 months (Q1-Q3: 5.2-81.2) after clinical inactivity, uveitis relapse occurred in 25 of these 75 patients (33.3%). Patients who were considered poor treatment responders for their initial uveitis episode had a significantly higher risk of relapse after achieving clinical inactivity than good responders (adjusted HR=3.84, 95% CI: 1.28 to 11.51). 13 of the 25 relapsed patients experienced multiple uveitis relapse episodes, accounting for 78 eye-relapse episodes during the entire observation period. Over half (46 out of 78, 59.0%) of these episodes were anterior uveitis. A significant number of uveitis relapse episodes (31 episodes, 39.7%) were effectively managed with topical corticosteroids. CONCLUSIONS: Our results suggest that approximately one-third of patients with OTB will experience relapse after achieving clinical inactivity. The initial disease course and poor response to treatment predict the likelihood of relapse in the long-term follow-up. Topical corticosteroids were particularly effective in relapse presenting as anterior uveitis.

The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.

Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) is a complication of type 2 diabetes mellitus (T2DM). Lipoprotein(a) (Lp(a)) contributes to the progression of DR, but how is unclear. In homeostasis of the retinal microvasculature, myeloid-derived pro-angiogenic cells (PACs) also play a pivotal role, and fail to function properly in diabetic conditions. Here, we explored the putative contribution of Lp(a) from patients with T2DM with/without DR and healthy controls on inflammation and angiogenesis of retinal endothelial cells (RECs), and on PAC differentiation. Subsequently, we compared the lipid composition of Lp(a) from patients to that from healthy controls. Methods: Lp(a)/LDL obtained from patients and healthy controls were added to TNF-alpha-activated RECs. Expression of VCAM-1/ICAM-1 was measured using flowcytometry. Angiogenesis was determined in REC-pericyte co-cultures stimulated by pro-angiogenic growth factors. PAC differentiation from peripheral blood mononuclear cells was determined by measuring expression of PAC markers. The lipoprotein lipid composition was quantified using detailed lipidomics analysis. Results: Lp(a) from patients with DR (DR-Lp(a)) failed to block TNF-alpha-induced expression of VCAM-1/ICAM-1 in REC whereas Lp(a) from healthy controls (healthy control [HC]-Lp(a)) did. DR-Lp(a) increased REC angiogenesis more than HC-Lp(a) did. Lp(a) from patients without DR showed intermediate profiles. HC-Lp(a) reduced the expression of CD16 and CD105 in PAC, but T2DM-Lp(a) did not. Phosphatidylethanolamine content was lower in T2DM-Lp(a) than in HC-Lp(a). Conclusions: DR-Lp(a) does not show the anti-inflammatory capacity seen with HC-Lp(a), but increases REC angiogenesis, and affects PAC differentiation less than HC-Lp(a). These functional differences in Lp(a) in T2DM-related retinopathy are associated with alterations in the lipid composition as compared to healthy conditions.

The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies.

Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether Mycobacterium tuberculosis (Mtb) is present in the ocular tissues, elicits a heightened immune response without Mtb invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-Mtb interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant Mtb strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary.

Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.

Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.

Evaluation of pre-processing methods for tear fluid proteomics using proximity extension assays.

Tear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the analysis and between-study comparisons. We studied two different pre-processing methods, specifically the use of punches of the strip versus elution of the strip in a buffer. Tear fluid filled Schirmer strips were collected from 5 healthy participants, and divided into two halves over the length of the strip. In either part, punches or eluates were obtained from 4 different locations, from the first part touching the eye (head) to the end, to assess the protein distribution along the strips. The levels of 92 inflammatory proteins were measured in the punches/eluates using proximity extension assays. The punch method yielded higher protein detectability compared to the elution method (76% vs 66%; p ≤ 0.001). Protein expression level was found to be slightly higher in the head of the strip, however, 3 out of 5 punches from the head failed quality control. Protein expression levels over the remaining parts of the strips were similar. Our study showed beneficial use of punches of any part of the strip except the head in future biomarker research.

Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response.

PURPOSE: Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach. METHODS: Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed. RESULTS: Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found. CONCLUSIONS: Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.

Vitreous proteomics, a gateway to improved understanding and stratification of diverse uveitis aetiologies.

PURPOSE: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. METHODS: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden's indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. RESULTS: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. CONCLUSION: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis.

CAUSES AND CLINICAL MANIFESTATIONS OF MASQUERADE SYNDROMES IN INTRAOCULAR INFLAMMATORY DISEASES.

OBJECTIVE: To identify the clinical characteristics and prevalence of neoplastic and nonneoplastic inflammatory masquerade syndromes (IMSs) in a tertiary center and determine the useful diagnostic tests. METHODS: A retrospective cohort study of consecutive 1906 patients diagnosed with intraocular inflammatory disease. RESULTS: Of all patients initially diagnosed with intraocular inflammatory disease, we identified 116 (6%) patients with noninflammatory causes (neoplastic IMSs in 36/116; 31% and nonneoplastic IMSs in 52/116; 45%). In addition, 26 patients (22%, 1.4% of all) had drug-induced uveitis and 2 (2%, 0.1% of all) had paraneoplastic uveitis. The large B-cell lymphoma was the most common neoplastic IMS (78%), and the major clinical features were presence of cells and floaters in the vitreous (69%) and chorioretinal lesions (33%). The causes of nonneoplastic IMSs included retinal vascular disorders (38%), hereditary retinal diseases (31%), and degenerative ocular disorders (19%). The common clinical manifestations consisted of chorioretinal scars (27%), small white-yellow retinal lesions (17%), and leaking vessels on fluorescein angiography (14%). CONCLUSION: Noninflammatory causes were determined in 6% of a large population with initial diagnosis of intraocular inflammatory disease. Although neoplastic IMS was commonly characterized by vitreous cells and opacities, most common definitive diagnoses in nonneoplastic IMS encompassed diverse retinal disorders.

The role of antibody indexes in clinical virology.

BACKGROUND: Serological techniques are an essential part of the diagnostic tools used in clinical virology. Among these techniques, antibody indexes are not novel, but do require specific expertise. Their niche has expanded substantially in recent years due to increasing evidence of their performance to diagnose viral infections. OBJECTIVES: This narrative review describes the background and clinical applications of antibody indexes. The first objective is to provide an overview of the theoretical background, insights for implementation, limitations and pitfalls. The second objective is to review the available evidence for the diagnostic performance, with a specific focus on viral encephalitis and uveitis. SOURCES: A comprehensive literature search was performed in PubMed, including original studies and reviews, with no time limit on the studies included. The following search terms were used: antibody index, Goldmann-Witmer coefficient, Reibergram, viral encephalitis, viral uveitis, herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, rubella virus, measles virus, enterovirus, influenza virus, flaviviruses. CONTENT: Antibody indexes can support the diagnosis of a spectrum of viral infections in immune privileged sites such as the central nervous system and the eye, through the demonstration of virus-specific intrathecal or intraocular antibody production. This is especially useful in situations where PCR has a lower positivity rate: infections with rapid viral clearance due to natural immunity or treatment and chronic stages of viral infections. IMPLICATIONS: Antibody indexes expand the clinical microbiologist's diagnostic toolbox. Careful interpretation of the results of these assays is crucial and further standardization of methods is required to improve interchangeability of results between laboratories.

No Evidence for Circulating Retina Specific Autoreactive T-cells in Latent Tuberculosis-associated Uveitis and Sarcoid Uveitis.

Purpose: To detect circulating retina-specific autoreactive CD4+ T-cells and antiretinal antibodies (ARA) in latent tuberculosis (TB)-associated uveitis or sarcoid uveitis patients.Methods: The presence of crude retinal extract (RE) autoreactive CD4+ T-cells was determined by a highly sensitive flowcytometric-based technique examining co-expression of CD25 and CD134 (OX40) on RE stimulated PBMC. The presence of ARA in available matched serum samples was assessed by indirect immunofluorescence.Results: No autoreactive CD4+ T-cells against RE could be detected in either latent TB-associated uveitis or sarcoid uveitis patients, while ARA were detected in the serum of the majority (5/6) of latent TB-associated uveitis and all (3/3) sarcoid uveitis patients.Conclusion: Even with the use of this highly sensitive flowcytometric technique circulating retina-specific autoreactive CD4+ T-cells could not be detected. In contrast, ARA were detected in the majority of patients indicating an adaptive humoral immune response toward retinal antigens had occurred.

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma.

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-1ß) 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.

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract.

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)-1ß, 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.

Autoantibody profiling in intraocular fluid of patients with uveitis.

A high prevalence of serum antiretinal antibodies (ARAs) in patients with uveitis has been previously described, though their clinical role remains elusive. Assessment of intraocular ARAs may provide further insight into the pathogenesis of diverse uveitis entities. In this study we investigate the prevalence of multiple specific anti-ocular antibodies (AOcAs), including ARAs, in intraocular fluid of patients with uveitis. Autoantibody profiling with 188 different ocular antigens was performed by a multiplex immunoassay with intraocular fluid samples of 76 patients with uveitis. Clinical data from uveitis patients were collected and statistical analyses were executed to evaluate associations between intraocular AOcAs and clinical characteristics. Controls consisted of 19 intraocular fluid samples from cataract patients. A spectrum of 22 different AOcAs was present in higher levels in patients with uveitis than in controls (p < 0.05), but in moderately elevated titers (<2x). High elevations of intraocular AOcAs in uveitis (>5x compared to cataract) were observed in varicella zoster virus-induced uveitis, multiple sclerosis-associated uveitis and patients with unexplained uveitis but positive quantiferon test. Presence of macular edema was associated with increased intraocular levels of tyrosinase antibodies. Our results show that patients with uveitis are characterized by the presence of a broad spectrum of moderately elevated levels of intraocular AOcAs, and high intraocular AOcA levels were found in several specific uveitis entities. This study favors secondary production of AOcAs and not their inciting role.

Three-dimensional tubule formation assay as therapeutic screening model for ocular microvascular disorders.

PURPOSE: This study is aimed to adapt a three-dimensional (3-D) in vitro angiogenesis model to the ophthalmology field using retinal endothelial cells (REC). This system is applied to assess the angiogenic capacity of aqueous humor (AH) from patients with ocular disorders, and to test the effect of VEGF inhibitor (aflibercept) on induced angiogenesis. METHODS: Human REC and umbilical vein endothelial cells (HUVEC) and pericytes were co-cultured in a gel matrix with 25-200 ng/ml pro-angiogenic growth factors (GF). AH from patients with cataract, glaucoma or proliferative diabetic retinopathy (PDR) was tested in the REC-pericyte co-culture. Aflibercept was then introduced to the co-culture containing PDR AH. The surface area and total tubule length were measured using Image J. RESULTS: Optimal GF concentrations at 200 ng/ml induced angiogenesis by REC as well as HUVEC, while vessel formation by both cell types was strongly reduced using 25-50 ng/ml GF. Addition of AH from the PDR patient triggered tubule formation by REC at low GF concentration. Aflibercept, however, significantly inhibited angiogenesis induced by PDR AH, but showed no significant influence on other conditions. CONCLUSION: REC can be applied efficiently in the 3-D in vitro angiogenesis model as a diagnostic tool to assess the AH angiogenic status and to validate new anti-angiogenic therapeutic compounds prior to clinical trial.

Autoimmunity in uveitis.

PURPOSE: Recent insights into the pathogenesis of immune-mediated diseases proposed a new classification, which includes autoimmune and auto-inflammatory diseases. The prevalence of specific autoimmune and auto-inflammatory diseases in uveitis and/or scleritis is not yet known. In this study, we examine the presence of systemic immune-mediated diseases in patients with uveitis and/or scleritis and put a special emphasis on autoimmune disorders by reporting on their clinical manifestations and visual prognosis. METHODS: In this retrospective study, we reviewed data of 1327 patients presenting with uveitis and/or scleritis between January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. All patients with noninfectious uveitis and/or scleritis were classified according to novel criteria for immune-mediated diseases. Various clinical data, including visual acuity (VA), of patients with uveitis of autoimmune origin were registered during 5-year follow-up. RESULTS: The origin of uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto-inflammatory and in 14% (180/1327) mixed autoimmune/auto-inflammatory. Patients with classical autoimmune connective tissue disease (N = 17) suffered mostly from rheumatoid arthritis and granulomatosis with polyangiitis and exhibited predominantly scleritis (53%). After 5 years of follow-up, none of the eyes of these patients developed legal blindness (VA of <0.1). The VA in patients with uveitis associated with autoimmune neuro-ophthalmological diseases (multiple sclerosis and neuromyelitis optica; N = 27) remained stable over time. CONCLUSION: 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.

Antiretinal antibodies in central serous chorioretinopathy: prevalence and clinical implications.

PURPOSE: To investigate the possible role of autoimmune reactions directed against retinal tissue in central serous chorioretinopathy (CSC), by analysing the presence of serum antiretinal antibodies (ARAs) and establishing their clinical relevance. METHODS: Sixty-three patients with CSC were included, and clinical characteristics were collected. Serum samples of all patients with CSC, 101 uveitis patients and 60 healthy donors were analysed for the presence of ARAs by indirect immunofluorescence. Furthermore, all CSC serum samples were analysed on Western blot. Correlations between laboratory findings and clinical features of CSC were determined by logistic regression. RESULTS: Antiretinal antibodies (ARAs) were present in 54% of the patients with CSC, in 46% of uveitis patients (p = 0.153) and in 17% of healthy controls (p < 0.001). The majority of ARAs in CSC were directed against photoreceptors (27%), which occurred significantly more often compared to uveitis patients (15%, p = 0.039) and to healthy controls (5%, p = 0.003). No associations between clinical CSC characteristics and the presence of ARAs were found. CONCLUSION: Serum ARAs are present in more than half of the patients with CSC, and especially, ARAs directed against photoreceptors were detected more frequently compared to both healthy controls and uveitis patients. Further research is warranted to unravel the role of ARAs in the pathogenesis of CSC.