Using paired t-test statistical analysis,authors studied the features of hemorrheology in 13 cases of anterior uveitis,16 cases of pan-uveitis,and 15 cases of Behccedil;et' syndrome.The study showed that serous viscocity(at 230 s-1)in anterior uveitis patient group was higher than that of the control group,P＜0.02; that blood viscocity at high shear rate(230 s-1)in pan-uneitis patient group was markedly elevated and the difference between patient and control group was sighificant,P＜0.005; and that blood viscocity at both high(230 s-1)and low shear rate(5.75 s-1)in Behcet' syndrome grou was elevated,and the differences were significant as compared to the controls(P＜0.01,P＜0.05).the high blood viscocity in uveitis and Behcet' syndrome patients was analyzed and discussed in the paper.We thought that the treatment for uveitis and Behcet' syndrome should include lowering blood viscocity and improving the plasticity of red blood cells. （Chin J Ocul Fundus Dis,1993,9:70-72）
ObjectiveTo observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)-related uveitis after hematopoietic stem cell transplantation (HSCT).MethodsA retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12±12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.ResultsAll eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.ConclusionCMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (＞3 months).
ObjectiveTo investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice. MethodsTwelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23Rlentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. ResultsCompared with the LV-Ctrlgroup, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group (t=－2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23Rgroup were higher than those of LV-Ctrl group, and the difference was statistically significant (t=－4.429, －6.578, －7.768, －10.183, －6.325, －7.304, －4.841, －6.872; P＜0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant (t=－4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23RmRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant (Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant (t=－6.313,－5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant (t=－5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant (t=－4.290, 3.700; P=0.002, 0.006). ConclusionIL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.
Vaccine-associated uveitis (VAU) usually refers to a rare adverse reaction that occurs after vaccination. The clinical manifestations of VAU are most often anterior with mild symptoms and responded promptly to topical corticosteroids. However, more severe forms of posterior and panuveitis may also occur, such as multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada syndrome, and acute posterior multifocal placoid pigment epitheliopathy. The pathogenesis of VAU is still unclear. Currently, it mainly includes vaccine Shoenfeld syndrome, type Ⅲ hypersensitivity reaction caused by immune complex deposition, direct infection with live attenuated vaccine, and molecular mimicry theory. VAU is self-limiting, and most patients heal without treatment. In the future, it is recommended to ask all patients with uveitis about their recent vaccination history in the clinic. For patients with inactivated vaccine or recombinant/subunit vaccination history, the possibility of developing Shoenfeld syndrome should be considered, and the history, signs and symptoms related to autoimmune diseases should be carefully looked for.
Anti-tumor necrosis factor-α monoclonal antibody agents have been widely applied in the management of autoimmune diseases. Among them, Adalimumab and Infliximab have been used for years in clinical practice in treating non-infectious uveitis and achieved satisfactory effects and safety. However, no guideline or expert consensus for their usage is available in China currently. It hopefully promotes standardized clinical application of anti-tumor necrosis factor -α monoclonal antibody in treating non-infectious uveitis, together with other senior experts in uveitis, the Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association form this evidence-based recommendations for clinicians’ reference.
As a new treatment option after conventional corticosteroids and immunomodulatory drugs, biologics have been widely used in the clinical management of non-infectious uveitis in many countries due to their approved efficacy and safety. Anti-tumor necrosis factor-alpha monoclonal antibody is the most commonly used one. However, the guidance on its standardized application is lacking. The Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association compiled the Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody. This evidence-based consensus is made according to the principle of consensus building and combines the clinical experience of the experts. Twelve recommendations are formatted on the application of Adalimumab and Infliximab. The interpretation of this consensus point will help improve the normative and effective application of anti-tumor necrosis factor-alpha monoclonal antibody in ophthalmologists, rheumatologists and immunologists.
Iron death is an alternative to normal cell death and is regulated by a variety of cellular metabolic pathways. Iron death has become a hot topic of research because it can cause damage to various organs and degenerative diseases in the body. Metabolism, signalling pathways, endoplasmic reticulum stress, and immune cells can all affect the occurrence of iron death, and the blood-retina destruction induced by iron death plays an important role in autoimmune uveitis. Exploring the components of the blood-retina regulatory mechanism of iron death in autoimmune uveitis can lead to the search for targeted drug targets, which can provide a new research idea for the subsequent study of the diagnosis and treatment of autoimmune uveitis.
Objective To investigate the clinical efficacy and factors influencing treatment of pediatric noninfectious uveitis with Adalimumab (ADA). MethodsA retrospective clinical study. A total of 86 pediatric patients with non-infectious uveitis, diagnosed and treated with ADA at Department of Uveitis Specialist of Xi'an People's Hospital (Xi' an Fourth Hospital) from January 1, 2021 to December 31, 2023, were included in this study. The age of all patients was ≤16 years. Among them, 55 (63.95%, 55/86) patients received ADA combined with one immunosuppressive agent, 28 (32.56%, 28/86) patients received ADA combined with ≥2 immunosuppressive agents, and 3 (3.49%, 3/86) patients received ADA alone without any immunosuppressive agents. All patients underwent best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The thickness of the retinal nerve fiber layer (RNFL) in the macular region was measured using an OCT device. The cumulative treatment effectiveness rate at 12 months post-treatment was evaluated using the Kaplan-Meier survival analysis. Multivariate analysis was performed using the Cox proportional hazards regression model, and the optimal predictive model was selected based on the Bayesian information criterion. The association between different treatment regimens and various clinical outcomes was assessed.ResultsAmong the 86 pediatric patients, 42 were male and 44 were female, with a mean age of (10.47±3.23) years. The distribution of uveitis types was as follows: anterior uveitis in 37 cases, intermediate uveitis in 15 cases, posterior uveitis in 10 cases, and panuveitis in 24 cases. Anterior chamber cells (ACC), keratic precipitates, and synechiae were present in 66, 55, and 38 cases, respectively. The cumulative treatment effectiveness at 12 months was 85.1% [95% confidence interval (CI) 71.9-92.2], with a median time to treatment effectiveness of 3 months. Compared with baseline, after 6 months of treatment, the BCVA, RNFL thickness (Z=−6.323, −8.017), and the grading of ACC and vitreous haze (χ2= −6.917, −5.027) showed significant improvement, with statistically significant differences (P＜0.05). Multivariate analysis revealed that ACC (hazard ratio=22.31, 95%CI 2.43-204.68) and anterior uveitis (hazard ratio=3.88, 95%CI 2.03-7.42) were significantly associated with treatment effectiveness (P＜0.05). Patients with ACC had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 95.5% (95%CI 86.3-98.5). Patients with anterior uveitis had a median time to treatment effectiveness of 2 months, with a 12-month cumulative treatment effectiveness of 97.3% (95%CI 81.3-99.6). Patients without anterior uveitis had a median time to treatment effectiveness of 5 months, with a 12-month cumulative treatment effectiveness of 76.7% (95%CI 54.1-88.2). The cumulative recurrence risk at 12 months was 15.6% (95%CI 6.2-24.1). ConclusionADA is safe and effective in treating pediatric non-infectious uveitis, and ACC and anterior uveitis are associated with response rate.
Pediatric uveitis is an inflammatory disease involving iris, ciliary body and choroid. Compared with adult uveitis, pediatric uveitis has insidious onset and is easy to delay treatment. In recent years, biological agents have made remarkable progress in the treatment of non-infectious uveitis (NIU) in children. Anti-tumor necrosis factor-alpha drugs represented by Adalimumab have shown good effects in the control of inflammation, the saving of glucocorticoids, the frequency of uveitis attacks and the improvement of visual prognosis. At the same time, other biologics such as B cell antagonists, T cell antagonists, interleukin-6 antagonists and Janus kinase inhibitors were also gradually tested in children with NIU, bringing good news to children who failed to respond to anti-tumor necrosis factor-alpha drugs. With the in-depth understanding of the diagnosis and treatment of NIU children by clinicians, as well as the characteristics and therapeutic application of various biological agents, it is helpful to develop a more diversified and individualized treatment plan for children, so as to save the vision of children and children's families.