Comprehensive evaluation of functional vision, quality of life, and cognitive ability in pediatric uveitis.

BACKGROUND: Pediatric uveitis may cause severe impairment of vision in children and affect their quality of life as well as cognitive ability. This study aims to evaluate the functional vision, visual-related and health-related quality of life, and cognitive ability in pediatric uveitis. METHODS: Children with uveitis aged 5-16 years old completed six validated instruments to assess functional visual ability with Cardiff Visual Ability Questionnaire for Children (CVAQC), vision-related quality of life with Impact of Vision Impairment for Children (IVI-C), health-related quality of life with Pediatric Quality of Life Inventory (PedsQL), cognitive ability with Chinese Wechsler Intelligence Scale for Children (C-WISC), and depression and anxiety evaluation with Hospital Anxiety and Depression Scale (HAD). RESULTS: The CVAQC, IVI-C, and PedsQL scores of pediatric uveitis were significantly lower than that of normal levels. Full-scale intelligence quotient (IQ) and performance IQ were significantly lower in pediatric uveitis patients with impaired vision in their best eye (visual acuity < 0.3) compared to those with a vision equal to or better than 0.3. Verbal IQ was significantly lower in male pediatric uveitis patients with impaired vision compared to those with a vision equal to or better than 0.3. Additionally, parents of pediatric uveitis patients with impaired vision generally had lower educational levels than parents of those with a vision equal to or better than 0.3. CONCLUSIONS: Impaired vision caused by pediatric uveitis has a significant impact on children's functional visual ability and quality of life. The development of cognitive function in pediatric uveitis is also significantly hindered.

Blister Pack Ingestion in an Elderly Patient With a Communication Barrier: A Case Report.

Foreign body ingestion is a common problem among elderly patients and can pose a serious health risk, particularly for those with communication barriers, cognitive impairments, or obscure medical histories. This report presents the case of a 67-year-old female inpatient who had a language communication barrier and accidentally ingested a blister pack. Effective communication was facilitated through an interpreter, and prompt endoscopic intervention was conducted to remove the foreign body safely. The patient was discharged with no further symptoms during follow-up. This case highlights the importance of prompt evaluation and intervention for foreign body ingestion in elderly patients, particularly those with communication barriers.

A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.

Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is -7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is -0.8 letters (95% CI, -6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.

TET2-mediated upregulation of 5-hydroxymethylcytosine in LRRC39 promoter promotes Th1 response in association with downregulated Treg response in Vogt-Koyanagi-Harada disease.

DNA 5-Hydroxymethylcytosine (5-hmC), an oxidative reaction mediated by the ten-eleven translocation (TET) family, has been reported to play an essential role in the progression of auto-inflammatory and autoimmune diseases. By far, little is known about the effect of DNA 5-hmC and the TET family on the development of Vogt-Koyanagi-Harada (VKH) disease. In this study, we discovered that the global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET2 at both mRNA and protein levels in CD4+T cells from active VKH patients compared to healthy controls. Integrated analysis of DNA 5-hmC pattern and transcription profile of CD4+ T cells revealed that 6 candidate target genes were involved in the development of VKH disease. The promoter 5-hmC and mRNA levels of leucine rich repeat containing 39 (LRRC39) were verified to be elevated in active VKH patients. Functional experiments showed that TET2 could up-regulate LRRC39 mRNA expression by increasing the promoter 5-hmC level of LRRC39 in CD4+ T cells from active VKH patients. Up-regulated LRRC39 expression could increase the frequencies of IFN-γ+ and IL-17+ CD4+ T cells as well as the secretions of IFN-γ and IL-17 in association with the decreased frequency of CD4+CD25+FOXP3+ regulatory T (Treg) cells and the reduced production of IL-10. Additionally, restoration of LRRC39 rescued TET2-silencing-mediated reduced frequency of IFN-γ+ CD4+ T cells and increased frequency of CD4+CD25+FOXP3+ Treg cells. Collectively, our study reveals a novel axis, the TET2-5-hmC-LRRC39-Th1/Treg responses axis, in the pathogenesis of VKH and provides a potential target for further investigation into the epigenetic therapy of this disease.

Vogt-Koyanagi-Harada disease in pediatric, adult and elderly: clinical characteristics and visual outcomes.

PURPOSE: To depict a whole spectrum of clinical feartures and visual prognosis among pediatric, adult, and elderly Vogt-Koyanagi-Harada disease (VKH) patients. METHODS: Retrospective chart review was conducted in 2571 VKH patients diagnosed from April 2008 to January 2022. Based on age of disease onset, patients were divided into pediatric (age ≤ 16 years), adult (16 < age < 65 years), and elderly (age ≥ 65 years) VKH group. Ocular and extraocular manifestations were compared among these patients. Visual outcomes and complications were evaluated using logistic regression models and restricted cubic splines analysis. RESULTS: The median follow-up time was 48 (IQR, 12-60) months. Pediatric, adult and elderly VKH were found in 106 (4.1%), 2355 (91.6%), and 110 (4.3%) patients, respectively. All of the patients showed similar ocular manifestations in the context of disease phasing. The proportion of neurological and auditory manifestations in pediatric (42.3% and 7.5%) VKH patients was significantly lower than that in adults (66.5% and 47.9%) and elderly (68.2% and 50%) (both p < 0.0001). An increased risk of macular abnormalities was seen in adults (OR, 3.43; 95% CI, 1.62-7.29) compared with elderly VKH. An inverted-U-shaped pattern was observed between disease onset age and a poor visual outcome (visual acuity 6/18 or worse) according to OR value in VKH patients. The highest risk of BCVA ≤ 6/18 was observed in 32 years at disease onset (OR, 1.51; 95% CI, 1.18-1.94). A higher risk of visual loss was observed in adult VKH patients (OR, 9.06; 95% CI, 2.18-37.6) compared with elderly VKH patients. And stratified by macular abnormalities, the interaction test was not significant (P = 0.634). CONCLUSION: Our study identified, for the first time, a whole spectrum of clinical features of VKH based on a large cohort of Chinese patients. Adult VKH patients have an increased risk of poor visual outcomes, possibly due to increased frequency of macular abnormalities.