Proteomic analysis of human aqueous humor from fuchs uveitis syndrome.

Fuchs uveitis syndrome (FUS) is a commonly misdiagnosed uveitis syndrome often presenting as an asymptomatic mild inflammatory condition until complications arise. The diagnosis of this disease remains clinical because of the lack of specific laboratory tests. The aqueous humor (AH) is a complex fluid containing nutrients and metabolic wastes from the eye. Changes in the AH protein provide important information for diagnosing intraocular diseases. This study aimed to analyze the proteomic profile of AH in individuals diagnosed with FUS and to identify potential biomarkers of the disease. We used liquid chromatography-tandem mass spectrometry-based proteomic methods to evaluate the AH protein profiles of all 37 samples, comprising 15 patients with FUS, six patients with Posner-Schlossman syndrome (PSS), and 16 patients with age-related cataract. A total of 538 proteins were identified from a comprehensive spectral library of 634 proteins. Subsequent differential expression analysis, enrichment analysis, and construction of key sub-networks revealed that the inflammatory response, complement activation and hypoxia might be crucial in mediating the process of FUS. The hypoxia inducible factor-1 may serve as a key regulator and therapeutic target. Additionally, the innate and adaptive immune responses are considered dominant in the patients with FUS. A diagnostic model was constructed using machine-learning algorithm to classify FUS, PSS, and normal controls. Two proteins, complement C1q subcomponent subunit B and secretogranin-1, were found to have the highest scores by the Extreme Gradient Boosting, suggesting their potential utility as a biomarker panel. Furthermore, these two proteins as biomarkers were validated in a cohort of 18 patients using high resolution multiple reaction monitoring assays. Therefore, this study contributes to advancing of the current knowledge of FUS pathogenesis and promotes the development of effective diagnostic strategies.

TNFAIP8 overexpression aggravates retinal pathophysiological features of diabetic retinopathy.

Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1ß, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.

HIGH LONG-TERM DRUG-FREE REMISSION RATE FOR ACUTE VOGT-KOYANAGI-HARADA DISEASE WITH AN APPROPRIATE IMMUNOSUPPRESSIVE REGIMEN.

PURPOSE: To report the clinical profile and outcomes of acute Vogt-Koyanagi-Harada disease with a strict immunosuppression regimen and investigate the risk factors for a prolonged disease course. METHODS: A total of 101 patients with acute Vogt-Koyanagi-Harada (202 eyes) with more than 24 months of follow-up were recruited from January 2011 to June 2020. They were divided into two groups according to the interval between the onset of Vogt-Koyanagi-Harada and treatment. Oral prednisone was gradually tapered off by a diminished dose according to a relatively strict protocol. Patient responses to the treatment regimen were classified as long-term drug-free remission or chronic recurrent. RESULTS: Ninety-six patients (95.0%) achieved long-term drug-free remission without recurrence, while 5 (5.0%) had chronic recurrence. Most patients achieved good best-corrected visual acuity (90.6% ≧20/25). A generalized estimation equation model demonstrated that time of visit, ocular complications, and cigarette smoking were independent risk factors for a longer disease course, and smokers required a higher drug dose and longer treatment course than nonsmokers. CONCLUSION: An immunosuppressive regimen with an appropriate tapering speed can lead to long-term drug-free remission in patients with acute Vogt-Koyanagi-Harada. Cigarette smoking significantly affects ocular inflammation.

Outcomes of retinal pigment epithelial detachment in Vogt-Koyanagi-Harada disease: a longitudinal analysis.

BACKGROUND: The aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course. METHODS: The retrospective study enrolled a total of 470 eyes with VKH, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (the CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups. RESULTS: CSC developed at the site of the PED in 5 of the 12 eyes with PED, while in the remaining 7 eyes PED gradually resolved following therapy. The prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P = 0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P = 0.03). CONCLUSION: PEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of classic CSC in VKH cases.

Comparison of the clinical features between posterior scleritis with exudative retinal detachment and Vogt-Koyanagi-Harada disease.

PURPOSE: This study aims to analyse the differences in clinical characteristics between VKH disease and PS with exudative retinal detachment (ERD). METHODS: The medical records of 18 eyes of 12 patients with PS accompanied by ERD and 32 eyes of 16 patients with VKH disease were retrospectively reviewed. RESULTS: Single ERD was more common in PS, while hyperreflective dots, multiple ERD, retinal pigment epithelium folds were more common in VKH disease on OCT. Both posterior coat thickness and choroid thickness were higher in VKH eyes. "T" sign was observed in 6 of 18 eyes (33.3%) in the PS group, whereas in none of the eyes of VKH disease. No significant differences were shown in FA imaging between PS and VKH cases. Relapse occurred in 12 eyes (66.7%) in PS group, mainly in the posterior segment, while 6 eyes (18.8%) experienced recurrence in the anterior segment in VKH group. CONCLUSION: There are characteristic differences in multimodal imaging parameters and clinical course between VKH and PS with ERD.

Comprehensive Proteomic Profiling of Aqueous Humor in Idiopathic Uveitis and Vogt-Koyanagi-Harada Syndrome.

Idiopathic uveitis (IU) and Vogt-Koyanagi-Harada (VKH) syndrome are common types of uveitis. However, the exact pathological mechanisms of IU and VKH remain unclear. Proteomic analysis of aqueous humor (AH), the most easily accessible intraocular fluid and a key site of uveitis development, may reveal potential biomarkers and elucidate uveitis pathogenesis. In this study, 44 AH samples, including 12 IU cases, 16 VKH cases, and 16 controls, were subjected to label-free quantitative proteomic analysis. We identified 557 proteins from a comprehensive spectral library of 634 proteins across all samples. The AH proteomic profiles of the IU and VKH groups were different from those of the control group. Differential analysis revealed a shared pattern of extracellular matrix disruption and downregulation of retinal cellular proteins in the IU and VKH groups. Enrichment analysis revealed a protein composition indicative of inflammation in the AH of the IU and VKH groups but not in that of the control group. In the IU and VKH groups, innate immunity played an important role, as indicated by complement cascade activation and overexpression of innate immune cell markers. Extreme gradient boosting (XGBoost), an efficient and robust machine learning algorithm, was subsequently used to screen potential biomarkers for classifying the IU, VKH, and control groups. Transferrin and complement factor B were deemed the most important and represent a promising biomarker panel. These proteins were validated by high-resolution multiple reaction monitoring (HR-MRM) in an independent validation cohort. A classification decision tree was subsequently built for the diagnosis. Our findings further the understanding of the underlying molecular mechanisms in IU and VKH and facilitate the development of potential therapeutic and diagnostic strategies.

Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with macular edema secondary to uveitis.

AIM: To assess the correlation between disorganization of the retinal inner layers (DRIL) and best-corrected visual acuity (BCVA) in patients with uveitis and macular edema (UME) who underwent systemic treatment using optical coherence tomography (OCT). METHODS: A retrospective clinical study of 23 patients (30 eyes) with DRIL and 23 patients (31 eyes) without DRIL secondary to UME were included. All patients underwent comprehensive ophthalmic examinations at baseline, 3, 6, and 12mo after local and systemic treatment. The OCT-based parameters included foveal center point thickness (FCPT), mean thickness (MT), and diameters of DRIL in horizontal and vertical directions. BCVA and OCT-based parameters were compared between the two groups. The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis. RESULTS: At the initial visit, the mean baseline FCPT was 441.03±128.68 µm in the eyes with DRIL and 337.26±99.31 µm in the eyes without DRIL (P=0.001). No significant differences were observed in MT (P=0.357). The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61 µm at baseline, respectively. There was significant improvement in BCVA and OCT-based parameters at 3, 6, and 12mo in all cases (P<0.001 for each timepoint). In addition, significant differences were detected in BCVA and OCT parameters between eyes with and without DRIL at each time point (P<0.01 for each timepoint). A greater DRIL range at baseline was associated with a worse baseline BCVA (transverse diameter of DRIL: r=0.875, P<0.001; vertical diameter of DRIL: r=0.622, P<0.001). The transverse diameter of baseline DRIL was found to be significantly correlated with the final BCVA (P=0.003). CONCLUSION: The improvement in BCVA is associated with DRIL in patients with UME. DRIL is an easy-to-determine and robust imaging biomarker that could help predict BCVA prognosis in eyes with UME.