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.

The Presence of Pigmentation on Central Anterior Lens Capsule in the Human Leukocyte Antigen B27-Associated Anterior Uveitis and Its Value in Clinical Diagnosis.

PURPOSE: To report on the value of presence of pigmentation on central anterior lens capsule (PioLe) in HLA B27- associated anterior uveitis (HLA B27-AU). METHODS: 268 patients (320 eyes) with AU were reviewed. Two diagnostic models to predict probability of HLA-B27-AU were developed. The first model included 6 variables (age, gender, unilaterality, presence of non-granulomatous keratic precipitates, hypopyon, and intraocular pressure (IOP). The second model was developed to investigate the added value of PioLe into the first model. RESULTS:      Unilaterality, presence of hypopyon, IOP <21 mmHg and PioLe were characteristic for HLA-B27 positive patients (P≤0.003 for all). All of 6 variables had area under receiver operating characteristic curves (AuROC) ≤ 60, but PioLe reached even higher value (65.5). Diagnostic model I and II had AuROC 76.3% (95%CI, 68.4%-84.2%) and 80.0% (95%CI, 72.6%-87.5%), respectively. CONCLUSIONS: Unilaterality, hypopyon, IOP <21 mmHg and presence of PioLe are clinical signs suggesting HLA B27- AU.

Prognostic factors of cataract surgery in patients with uveitis.

PURPOSE: To evaluate the long-term visual outcomes of patients with uveitis undergoing cataract surgery and to identify possible factors influencing the visual prognosis and the development of postoperative complications. METHODS: Retrospective study of all patients with uveitis who underwent cataract surgery between January 2015 and February 2020 in our tertiary referral center. RESULTS: A total of 78 eyes from 78 patients were included in the study. The best-corrected visual acuity (BCVA) improved in 86% of patients, and a BCVA of 0.5 or better was achieved in 57 (73%) patients. A significant correlation was shown between the preoperative and postoperative BCVA (Spearman r = 0.521, p < 0.01). Final BCVA differed between diverse anatomical uveitis entities (p = 0.047), and anterior uveitis demonstrated the best outcomes. Chronic uveitis resulted in a worse final BCVA than acute recurrent uveitis (p = 0.001). The presence of CME any time before the surgery and intermediate uveitis were associated with worse visual prognosis, while systemic therapy for uveitis before surgery and iris manipulation during surgery were not related to visual outcomes. Postoperative development of cystoid macular edema (CME) was closely associated with preexisting CME (p < 0.001) and intermediate uveitis (p = 0.01). CONCLUSIONS: Visual results of cataract surgery in patients with uveitis were beneficial, but limited visual outcomes were more frequently observed in patients with chronic uveitis and intermediate uveitis with a history of CME. In consequence, prevention, or adequate treatment of CME, especially in patients with intermediate uveitis, might result in better visual results of their cataract surgery.

Clinical and Microbiological Manifestations of Endogenous Endophthalmitis in Tertiary Care Hospital, Northern Thailand.

PURPOSE: To determine the characteristics, primary sources, pathogens, risk factors, and visual outcomes in patients with endogenous endophthalmitis (EE). METHODS: We performed a retrospective cohort study of 61 consecutive patients with EE (74 affected eyes) and reported on prevalence, clinical courses, prognostic factors and visual outcomes. RESULTS: Prevalence of EE was 5% of all patients with endophthalmitis. Among culture-positive cases (89%), Gram-positive species dominating (69%) followed by Gram-negative with 22% and fungal species with 9%. Regarding to visual outcomes, the mean visual acuity (VA, ETDRS letters) at baseline, 3-months, 6-months and 1-year follow-up was 0.85, 9, 8 and 9, respectively. Initial VA of hand movement or better (P 0.007) and bilateral infection (P 0.004) were associated with better visual outcome. CONCLUSION: The prognosis for EE remained poor despite aggressive and immediate treatment. The high suspicion, early diagnosis and prompt treatment are important factors that might lead to the better outcome.

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.

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.

Idiopathic Epiretinal Membranes: Visual Outcomes and Prognostic Factors

Objectives: To evaluate the associations between anatomical changes and visual outcomes in patients with idiopathic epiretinal membrane (ERM). Materials and Methods: We performed a prospective study of 130 consecutive idiopathic ERM patients and report their visual outcomes and the factors associated with visual outcome and anatomical changes. Results: Of 130 eyes of 130 patients, 87 eyes underwent surgery, while the remaining 43 eyes were observed. At 6-month follow-up, the best-corrected visual acuity (BCVA) increased in the whole population. Mean Early Treatment Diabetic Retinopathy Study letter score changed from 51 to 65 in the surgical group and from 67 to 68 in the non-surgical group. The surgical group had improvement in BCVA at all ERM stages and grades of disorganization of the retinal inner layers (DRIL) (p<0.01). In multivariable analysis of the surgical group, factors associated with BCVA of ETDRS 60 letters or more were no or mild DRIL and the absence of ellipsoid zone disruption at baseline (p=0.002 and p=0.034, respectively) and this statistically significant positive correlation was still maintained at 12-month follow-up. Conclusion: Baseline DRIL grade and presence of ellipsoid zone disruption were the most informative prognostic factors in patients with idiopathic ERMs. Patients with severe DRIL and/or advanced ERMs had improved vision after ERM removal.

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.

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.

Development of Acute Vogt-Koyanagi-Harada-like Syndrome during the Treatment Course with Vemurafenib for Metastatic Melanoma.

Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.

Causes of Hypertensive Anterior Uveitis in Thailand.

PURPOSE: To determine the prevalence of viral infections in patients with hypertensive anterior uveitis in Thailand from polymerase chain reaction (PCR) of aqueous humor. METHODS: Thirty-one patients with anterior uveitis with intraocular pressure (IOP) above 25 mmHg were included for PCR analysis for cytomegalovirus (CMV), herpes simplex (HSV), varicella-zoster (VZV), rubella, chikungunya and Zika virus. RESULTS: The prevalence of PCR-positive results was 32%, including 19% for CMV, 10% for HSV, and 3% for VZV; PCR for other tested viruses demonstrated negative results. PCR-positive patients exhibited satisfactory IOP control with antiviral and anti-glaucomatous treatment compared to PCR-negative patients, and more than half of PCR-negative patients required glaucoma surgery within 12 months (P = .01). CONCLUSION: PCR evidence of infection with herpes group viruses was found in one-third of patients with hypertensive anterior uveitis; CMV being the most common pathogen. The PCR-positive group generally responded well to a combination of antiviral and anti-glaucoma treatment.

Prevalence of Positive QuantiFERON-TB Gold In-Tube Test in Uveitis and its Clinical Implications in a Country Nonendemic for Tuberculosis.

PURPOSE: To report on the prevalence and clinical implications of positive QuantiFERON-Gold (QFT-G) test results in the diagnostic evaluation of a large cohort of consecutive patients with uveitis in the Netherlands. DESIGN: Retrospective cross-sectional study. METHODS: This study included 710 consecutive patients who all underwent evaluation for uveitis including QFT-G testing. The ocular features, comorbidity, and abnormalities in diagnostic imaging and laboratory tests were registered for QFT-G-positive patients with uveitis. RESULTS: Of all patients, 13% (92/710) were positive for QFT-G. Previously treated tuberculosis (TB) was documented in 2 patients. Of all 92 QFT-G-positive patients, culture-proven active TB was observed in 1 case. The proportion of patients with uveitis of unknown etiology was higher in QFT-G-positive than in the QFT-G-negative patients (54/92, 59% vs 238/618, 39%; P = .0004). The uveitis features of QFT-G-positive patients were mainly nonspecific. Of all QFT-G-positive patients with uveitis, 17 patients had chest imaging changes suggesting either TB or sarcoidosis. Twenty-nine QFT-G-positive patients with otherwise unexplained uveitis completed antituberculous therapy (29/710; 4% of all included patients) with beneficial effect in most cases. CONCLUSION: The QFT-G tested positive in 13% of patients with uveitis in the Netherlands, whereas only sporadic patients had a documented previous or active TB infection. The proportion of patients with unexplained uveitis was higher in QFT-G-positive patients. Though the association between uveitis and a positive QFT-G test might be coincidental, the majority of treated QFT-G-positive patients with otherwise unexplained severe uveitis cause had a beneficial response to antituberculous therapy.

Clinical Manifestations, Prognosis, and Vaccination Status of Patients With Rubella Virus-Associated Uveitis.

PURPOSE: To assess the clinical and laboratory manifestations and vaccination status of uveitis patients positive for rubella virus (RV) in aqueous humor and investigate its relationship to Fuchs uveitis syndrome (FUS). METHODS: Retrospective study of all uveitis patients, positive for RV in aqueous humor analysis (polymerase chain reaction [PCR] and/or Goldmann-Witmer coefficient [GWC]) between January 2010 and October 2016 at the ophthalmology departments in the Erasmus Medical Center (Rotterdam) and University Medical Center Utrecht. Outcomes of aqueous analyses of FUS patients during this period were assessed. RESULTS: We included 127 patients (144 eyes) positive for RV in aqueous fluid: 23 (20%) by PCR, 120 (97%) by GWC, and 16 (13%) by both. The average age at first presentation was 37 years. Patients typically complained of blurred vision and exhibited a combination of unilateral anterior uveitis, keratic precipitates, vitritis, and absence of posterior synechiae, but the classical FUS was observed in a minority. The main cause of untreatable visual loss was glaucoma. Cystoid macular edema (CME) before intraocular surgery was not encountered. None of the unilateral cases developed involvement of the other eye. None of the patients was vaccinated against RV. All FUS patients, except 2 (5%), were positive for RV. CONCLUSION: RV-associated uveitis and FUS are not exchangeable. Chronic anterior uveitis, vitritis, early development of cataract, and the absence of posterior synechiae and CME characterize RV-associated uveitis. Almost all FUS cases had documented intraocular RV infection, but only some of the patients with RV-associated uveitis presented with FUS.

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.

Ocular Manifestations and Visual Outcomes of Behçet's Uveitis in a Thai population.

PURPOSE: To report on ocular manifestations and visual outcomes of Thai patients with Behçet's Uveitis (BU). METHODS: We reviewed medical records of 50 BU patients (31 males and 19 females). Ocular manifestations, treatment modalities, complications, and visual outcomes were registered. RESULTS: Ocular involvement was bilateral in 76% of patients, resulting in 89 affected eyes. Panuveitis and posterior uveitis were the most common types. Retinal vasculitis was noted in majority of affected eyes and specifically arteritis was noticed in 32/57(56%). Most patients received combination therapy of systemic corticosteroids and immunosuppressive agents (azathioprine 72%). At final visit, VA ≤20/200 was observed in 25 affected eyes (28%). Risk factors for poor visual outcome were poor visual acuity at presentation (p < 0.001) and development of optic atrophy (p = 0.01). CONCLUSIONS: Typical ocular manifestations of Thai patients with BU consisted of bilateral uveitis affecting posterior eye segment with high rate of complications and frequent visual loss.

Risk Factors for Development of Rhegmatogenous Retinal Detachment in Patients with Uveitis.

Purpose: To describe risk factors for development of rhegmatogenous retinal detachment (RRD) in patients with uveitis. Methods: We performed a retrospective review of 411 consecutive human immunodeficiency virus-negative patients with uveitis (571 affected eyes) and report on prevalence, risk factors and visual outcomes of patients with RRD. Results: Prevalence of RRD was 7% of all patients with uveitis. Multivariate analysis revealed that posterior uveitis and panuveitis were associated with RRD (P = 0.001). Strong association between RRD development and infectious uveitis was also observed (P = 0.009). Acute retinal necrosis (ARN) was firmly associated with RRD development (P = 0.016). Although anatomical success was obtained, functional outcome was poor. Poor visual outcomes at 6-month and 1-year follow-up were associated with initial VA < counting fingers (P = 0.05, P = 0.044). Conclusions: Prevalence of RRD in uveitis was 7% and development of RRD was encountered in posterior and panuveitis. Infectious uveitis (specifically ARN) formed a high risk for RRD.

ADALIMUMAB THERAPY FOR REFRACTORY BIRDSHOT CHORIORETINOPATHY.

PURPOSE: To report the outcome of using adalimumab to treat birdshot chorioretinopathy. METHODS: Retrospective case series of 19 patients (38 eyes) with HLA-A29-positive birdshot chorioretinopathy who received adalimumab treatment. Patients had been refractory to previous standard systemic immunomodulatory therapy. They received biweekly subcutaneous injections of 40 mg of adalimumab. Outcome measures were change in visual acuity, fluorescein angiography, and optical coherence tomography features, the concomitant use of immunosuppressive drugs, and the occurrence of adverse effects between 1 year before, at baseline, and after 1 year of adalimumab treatment. RESULTS: Mean Snellen visual acuity at 1-year follow-up was 20/28, an improvement from 20/43 at the start of the treatment (P = 0.011) and equal to the visual acuity 1 year before the treatment (20/29). Only 2 of the 9 patients who had complete fluorescein angiography and optical coherence tomography results after the 1 year of treatment were completely free of inflammation signs at the end of the follow-up. Half (53%) of 17 patients were receiving adalimumab monotherapy after 1 year of treatment, an increase from 21% at the start of treatment (P = 0.047). Three of the 19 patients reported possible side effects; 2 discontinued treatment within 1 year. CONCLUSION: The results suggest that adalimumab is effective at improving visual acuity and at tapering concomitant immunomodulatory therapy, in patients with refractory birdshot chorioretinopathy. However, complete remission is rarely achieved.

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.