Efficacy of Adalimumab in pediatric non-infectious uveitis with apparent and non-apparent anterior uveitis

Efficacy of Adalimumab in pediatric non-infectious uveitis with apparent and non-apparent anterior uveitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of Adalimumab in pediatric non-infectious uveitis with apparent and non-apparent anterior uveitis Chunbo Zhang, Xiaorong Xue, Jinan Xiao, Qiongge Li, Yuyao Zhai, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4540347/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Jan, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Adalimumab (ADA) has been used for treating various types of pediatric non-infectious uveitis. Existing studies lack an examination of the correlation between the clinical characteristics of uveitis and the success rate of ADA treatment. The present study is to identify the clinical characteristic of cases that is related to the response rate of ADA treatment. Methods A retrospective review of medical records was conducted for pediatric patients with non-infectious uveitis undergoing ADA treatment for a minimum of six months. The patients were stratified into two groups: apparent anterior uveitis (AAU) and with non-apparent anterior uveitis (NAAU). Outcomes including best-corrected visual acuity (BCVA), anterior chamber cell (ACC), vitreous haze (VH) grade, retinal nerve fiber layer (RNFL) thickness, fundus fluorescein angiography (FA) scores, as well as systemic immunosuppression therapy (IMT) and glucocorticoid load, were assessed. Treatment success was defined based on a composite outcome involving the aforementioned variables. Results The study included 59 patients (111 eyes), with 44 patients (83 eyes, 74.58%) falling into the AAU group and 15 patients (28 eyes, 25.42%) in the NAAU group. Following 6-month of ADA treatment in the AAU group, there was a significant improvement in BCVA ( p < 0.001), improved ACC ( p < 0.001) and VH ( p < 0.001), decreased RNFL thickness ( p < 0.001), reduced FA scores ( p < 0.001). Conversely, no significant differences were observed in BCVA, VH, RNFL thickness, FA scores between baseline and the 6-month follow-up visit in the NAAU group. There was also a significant decrease in systemic IMT and glucocorticoid dosing, comparing baseline to the 6-month follow-up visit in both the AAU ( p < 0.001) and NAAU groups ( p < 0.05). The rate of treatment success in the AAU group was significantly higher compared to that in NAAU patients (93.18% vs. 20%, p < 0.001). Conclusion ADA demonstrates superior efficacy in the treatment of pediatric non-infectious uveitis with AAU compared to NAAU. TNF-α inhibitor Adalimumab pediatric non-infectious uveitis anterior uveitis treatment Introduction Pediatric non-infectious uveitis is characterized by the persistence or recurrence of intraocular inflammation, posing a substantial risk of visual impairment in approximately one-third of affected individuals [ 1 ]. The management of most cases of pediatric non-infectious uveitis necessitates a systemic and prolonged treatment regimen, typically following a stepwise approach. Systemic glucocorticoids use in children and adolescents raises significant concerns due to growth retardation and other metabolic or endocrine side effects. Consequently, the overarching objective of long-term therapy is to achieve corticosteroid-free remission through the implementation of corticosteroid-sparing immunomodulatory agents for the management of chronic or recurrent pediatric uveitis [ 1 ]. Conventional corticosteroid-sparing immunomodulatory agents include methotrexate (MTX), azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus and cyclosporine (CsA) [ 2 ]. Despite the efficacy of these agents, a subset of patients remains refractory, exhibiting inadequate response to conventional immunosuppressants. In such instances, the therapeutic paradigm advances to include biologic agents, among which tumor necrosis factor alpha (TNF-α) inhibitors stand out as pivotal contributors to the evolving landscape of pediatric uveitis treatment [ 1 ]. Adalimumab (ADA), a fully humanized anti-TNF-α monoclonal antibody, has been recognized as a promising agent for treating noninfectious uveitis in adults and children [ 3 – 10 ]. Notably, the SYCAMORE study, a randomized, double blinded, placebo-controlled study, provided compelling evidence that the combination of ADA with MTX yielded a lower rate of treatment failure compared to MTX alone for treating juvenile idiopathic arthritis (JIA)-associated uveitis [ 10 ]. Moreover, ADA was efficacious in managing non-JIA chronic uveitis [ 11 ]. Despite these advancements, a subset of pediatric patients with uveitis within our clinical practice exhibit insufficient or no response to TNF-α inhibitor treatment. Other studies reported that pediatric uveitis cases of varied etiologies showed response rates ranging from 58.8–95.5% [ 6 , 12 – 15 ]. The substantial disparity in treatment success rates across different studies prompts a crucial inquiry into the identification of clinical features closely associated with the responsiveness to ADA treatment. Within this context, our clinical observations lead us to postulate that pediatric patients with non-infectious uveitis, specifically those presenting with apparent anterior uveitis (AAU), may have a more favorable response to ADA treatment than those with non-apparent anterior uveitis (NAAU) during the early stages of clinical intervention. Consequently, we conducted a retrospective analysis to systematically compare the efficacy of ADA treatment between these two groups at both baseline and the 6-month follow-up visit. Materials and methods Study Design and Patient Identification This retrospective study was conducted at a tertiary ophthalmic center in Shaanxi, China. Medical records of pediatric patients (age ≤ 16 years) with uveitis who visited the uveitis service of the ophthalmology department at Xi’an People’s Hospital (Xi’an Fourth Hospital) (Shannxi, China) between January 2021 and February 2023 were reviewed. The inclusion criteria were: a confirmed diagnosis of non-infectious chronic uveitis and treatment with ADA (Humira; AbbVie Inc., Ludwigshafen, Germany) or ADA biosimilars (Anjianning; BioRay Pharmaceutical Co., Ltd., Taizhou, Zhejiang province, CHN or QLETLI; Bio-Thera Solutions Ltd., Guangzhou, Guangdong province, CHN) for a duration exceeding 6 months. The initial dosage regimen consisted of 80 mg, followed by 40 mg after 1 week. Subsequently, a maintenance dose of 40 mg was administered every 2 weeks, while those weighing ˂30 kg received half the standard dose. Exclusion criteria comprised the presence of corneal or lens opacity hindering the visualization of the anterior chamber or fundus, or impeding optimal imaging using spectral-domain optical coherence tomography (OCT) devices. The anatomical classification of uveitis was determined according to the Standardization of Uveitis Nomenclature (SUN) Working Group [ 16 ]. The included patients were stratified into two groups: the apparent anterior uveitis (AAU) group and the non-apparent anterior uveitis (NAAU) group. Criteria for inclusion in the AAU group were patients exhibiting ACC grade ≥ 1 + at least one visit before initiation of ADA treatment, pupillary adhesion or band degeneration of the cornea. Inclusion in the NAAU group required patients to display an ACC grade ≤ 0.5 + during all visits, and the absence of pupillary adhesion and band degeneration of the cornea. This study protocol underwent rigorous evaluation by the Ethics Committee of Xi'an People's Hospital (Xi’an Fourth Hospital) (No.20220023). Considering the retrospective nature of this study, the requirement for informed consent was waived by the Ethics Committee. The study was done in compliance with the Declaration of Helsinki. Data Collection A comprehensive dataset of demographic and clinical characteristics was assembled, including gender, age, anatomical uveitis classification, uveitis etiology and ocular complication at the baseline visit. A thorough ophthalmic examination, such as best corrected visual acuity (BCVA) through a logarithmic visual acuity chart, intraocular pressure (IOP), slit-lamp examination of the anterior segment, and a detailed examination of the dilated vitreous and fundus, were performed at both baseline and follow-up visits. The use of concurrent systemic glucocorticoids and/or other immunosuppressive therapy were documented. Patients were scheduled for follow-up assessments based on their specific conditions between the baseline and 6-month follow-up visit. Grading of anterior chamber cell (ACC) count was executed in adherence to the SUN Working Group criteria [ 16 ]. Vitreous haze (VH) was evaluated by the Nussenblatt scale [ 17 ]. Retinal nerve fiber layer (RNFL) thickness measurements were obtained through optical coherence tomography (OCT) (Spectralis, Heidelberg Engineering, Germany). Assessment of retinal vascular leakage was evaluated by fluorescein angiography (FA) (Heidelberg Engineering, Germany). FA scores were independently evaluated by two ophthalmologists (Y.C. and J.-A.X.) based on the scoring system established by the Angiography Scoring for Uveitis Working Group (ASUWOG) [ 17 ]. The systemic immunosuppression therapy (IMT) load and glucocorticoid load were assessed utilizing a weighted semiquantitative scale for each prescribed medication as detailed in supplementary Table 1 to present a consolidated, single numeric score reflecting the overall immunosuppression load per unit body weight per day [ 18 ]. The improvement of outcomes was defined as follows: visual acuity increased by two or more lines; ACC or VH reduced two or more grades or to grade 0. The worsening of outcomes was defined as follows: visual acuity decreased by two or more lines; ACC or VH increased by two or more grades or to grade 4; The improvement or worsening of retinal vascular leakage detected by FA was assessed by two experienced ophthalmologists (YC and JA-X). Treatment success of uveitis was defined as the improvement of any one of the specified outcomes at the 6-month follow-up visit compared to the baseline visit in the eye exhibiting more severe intraocular inflammation, with no worsening of any outcome observed during the 6-month follow-up in the both eyes, and the prednisone dose reduced to ≤ 0.1 mg/kg/day at the 6-month follow-up visit. Statistical Analysis Descriptive statistics were used to report the demographic and clinical features of the patients. Demographics, clinical characteristics, the improvement of outcome variables and the rate of treatment success between the two groups were compared using the Wilcoxon rank sum test, Pearson's Chi-squared test, or Fisher's exact test, as appropriate. The outcome variables were evaluated using a mixed model for repeated measures (MMRM) and reported as the difference of marginal means of the two time point of measurement (baseline and month six) for both AAU and NAAU patients. The model included the paired eyes (left and right in same individual) and time point of measurement (baseline and 6-month follow-up visit) as fixed effects. Patient-specific effects enter the model as a random effect with normal distribution and an expected value of zero. The analysis was performed using the R statistical software version 4.3.2 (R Project for Statistical Computing). A significance level of p < 0.05 was considered indicative of a statistically significant difference. Results In this retrospective and nonrandomized study, we initially screened 68 consecutive pediatric patients with NIU who underwent ADA treatment. Four patients were lost to follow-up within the initial 6 months of ADA initiation. Two patients were unable to cooperate with the examination due to their young age, while two patients presented with heavy cataracts, and one patient exhibited severe corneal band degeneration, resulting in poor OCT image quality. These nine patients were excluded from the study, leaving 59 patients for analysis. Among the included patients, 44(83 eyes) were categorized into the AAU group (74.58%), and the remaining 15 (28 eyes) formed the NAAU group (25.42%). Baseline characteristics of the patients when ADA was initiated are summarized in Table 1 . Table 1 Baseline Characteristics of the Patients When ADA Was Initiated. Parameters AAU NAAU p Patients/eyes 44 (83) 15(28) - Age (years), median (range) 9.30(7.10,12.35) 9.60(7.95,13.00) 0.394 Sex (male/female) (26/18) (6/9) 0.200 Weight (30kg) 12/32 3/12 0.738 Bilateral/unilateral 39/5 13/2 > 0.999 Etiology of uveitis [No. (%)] Vogt–Koyanagi–Harada disease 3(6.82%) 0(0%) 0.564 Juvenile idiopathic arthritis 4(9.09%) 0(0%) 0.564 Behçet’s disease 3(6.82%) 0(0%) 0.564 Idiopathic uveitis 34(77.27%) 15(100%) 0.052 Anatomic types of uveitis [No. (%)] Anterior uveitis 29(65.91%) 0(0%) < 0.001 * Intermediate (+ anterior) uveitis 7(15.91%) 0(0%) 0.174 Intermediate (- anterior) uveitis 0(0%) 9(60%) < 0.001 * Posterior uveitis 0(0%) 6(40%) < 0.001 * Panuveitis 8(18.18%) 0(0%) 0.100 Complications [eye. (%)] 40(48.19%) 7(25.00%) 0.025 * Cataract [eye. (%)] 29(34.94%) 7(25.00%) 0.232 Ocular hypertension [eye. (%)] 7(8.43%) 0(0%) 0.255 Pupillary adhesion [eye. (%)] 29(34.94%) 0(0%) < 0.001 * Band degeneration of cornea [eye. (%)] 15(18.07%) 0(0%) 0.036 * macular cystoid edema [eye. (%)] 8(9.64%) 0(0%) 0.200 Duration before ADA treatment (months), median (range) 5.50(3.00, 11.25) 8.00(3.50, 12.00) 0.407 Systemic IMT therapy before baseline [No. (%)] 23 (52.27%) 10 (66.67%) 0.332 Methotrexate 11 (25%) 2 (13.33%) 0.482 Glucocorticoids + methotrexate 6 (13.64%) 4 (26.67%) 0.257 Glucocorticoids + cyclosporin A 1 (2.27%) 1 (6.67%) 0.447 Glucocorticoids + azathioprine 1 (2.27%) 1 (6.67%) 0.447 Mycophenolate mofetil 0 (0%) 1 (6.67%) 0.254 Glucocorticoids + cyclosporin A + azathioprine 0 (0%) 1 (6.67%) 0.254 Cyclosporin A + methotrexate 4 (9.09%) 0 (0%) 0.564 * p < 0.05 NAAU vs. AAU In AAU group, the BCVA showed a statistically significant improvement at the 6-month follow-up visit [-0.12, 95% CI (-0.15– -0.09), p < 0.001]. Similarly, RNFL thickness exhibited a significant decrease [-17.00, 95% CI (-19.68– -14.32), p < 0.001]. Thirty-eight patients (86.36%) had undergone FA at baseline and at the 6-month follow-up visit. The improvements in FA scores were attributed primarily to capillary leakage reduction, and were significant [-4.82, 95% CI (-5.45– -4.19), p < 0.001]. ACC [-2.73, 95%CI (-2.98– -2.49), p < 0.001] and VH [-0.34, 95%CI (-0.45– -0.24), p < 0.001] also showed significant improvement from baseline to the 6-month follow-up visit (Table 2 ). In contrast, the NAAU group exhibited no significant differences in BCVA [-0.02, 95% CI (-0.06–0.02), p = 0.382], RNFL thickness [-3.25, 95% CI (-6.72–0.22), p = 0.066], FA scores [-0.29, 95% CI (-1.36–0.78), p = 0.592] and VH [-0.04, 95%CI (-0.18–0.11), p = 0.620] (Table 3 ) between the baseline and 6-month follow-up visit. Reductions were noted in systemic IMT and glucocorticoid dosing comparing baseline to the 6-month follow-up visit in both the AAU [-3.59, 95% CI (-4.66– -2.52), p < 0.001], [-1.50, 95% CI (-2.20– -0.80), p < 0.001] (Table 2 ) and NAAU [-1.13, 95% CI (-2.11– -0.15), p = 0.026], [-0.87, 95% CI (-1.49– -0.24), p = 0.010] groups (Table 3 ). Table 2 Outcome Variables of 44 Patients (83 Eyes) in AAU Group at baseline and at 6-month Follow-up Visit. Variable Baseline 6 months Difference, (95% CI) p mean (95CI%) Patients/eyes 44/83 44/83 - - logMAR BCVA 0.18 (0.13–0.23) 0.06 (0.01–0.11) -0.12 (-0.15– -0.09) < 0.001 * RNFL(µm) 134.36 (130.83–137.89) 117.36 (113.83–120.89) -17.00 (-19.68– -14.32) < 0.001 * FA score # 8.09 (6.58–9.60) 3.27 (1.76–4.79) -4.82 (-5.45– -4.19) < 0.001 * ACC 3.00 (2.77–3.22) 0.26 (0.04–0.48) -2.73 (-2.98– -2.49) < 0.001 * VH 0.47 (0.34–0.61) 0.13 (-0.01–0.26) -0.34 (-0.45– -0.24) < 0.001 * IMT load 7.91 (7.13–8.69) 4.32 (3.54–5.10) -3.59 (-4.66– -2.52) < 0.001 * Glucocorticoids load 1.80 (1.21–2.38) 0.30 (-0.29–0.88) -1.50 (-2.20– -0.80) < 0.001 * Abbreviation: BCVA, best-corrected visual acuity; RNFL, Retinal nerve fiber layer thickness; FA, fluorescein angiography; IMT, immunosuppression therapy; CI, confidence interval. * p < 0.05, 6-month follow-up visit vs. baseline; # n = 72 Table 3 Outcome Variables of 15 Patiens (28 Eyes) in NAAU Group at Baseline and 6-month Follow-up Visit. Variable Baseline 6 months Difference (95% CI) p mean (95CI%) Patients/eyes 15/28 15/28 - - logMAR BCVA 0.26 (0.09–0.44) 0.25 (0.07–0.42) -0.02 (-0.06–0.02) 0.382 RNFL(µm) 124.10 (119.48–128.72) 120.85 (116.23–125.47) -3.25 (-6.72–0.22) 0.066 FA score 8.39 (7.07–9.72) 8.11 (6.78–9.43) -0.29 (-1.36–0.78) 0.592 VH 0.45 (0.22–0.67) 0.41 (0.19–0.64) -0.04 (-0.18–0.11) 0.620 IMT load 7.60 (6.23–8.97) 6.47 (5.09–7.84) -1.13 (-2.11 – -0.15) 0.026 * Glucocorticoid load 1.67 (0.69–2.64) 0.80 (-0.18–1.78) -0.87 (-1.49 – -0.24) 0.010 * Abbreviation: BCVA, best-corrected visual acuity; RNFL, Retinal nerve fiber layer thickness; FA, fluorescein angiography; IMT load, immunosuppression therapy load; CI, confidence interval. * p < 0.05 6-month follow-up visit vs. baseline Based on our defined criteria for the improvement of outcome variables, the improvement rates of VH, RNFL thickness and FA scores in the AAU group were significantly higher compared to those in the NAAU group. In addition, a higher proportion of patients in the AAU group were able to reduce prednisone dosage to less than 0.1 mg/kg/day compared to the NAAU group. The composite result showed that the treatment success rate of uveitis in the AAU group was substantially higher than that in the NAAU group (93.18% vs 20%, p < 0.001) (Table 4 ). Table 4 The Improvement of Outcome Variables and The Rate of Treatment Success After ADA Treatment. Variables AAU (n = 44) NAAU (n = 15) p BCVA 13/ 44 (29.55%) 1 /15 (6.67%) 0.090 ACC 39/44 (88.84%) N/A - VH 17/25 (68%) 2/11 (18.18%) 0.010 * FA 23 /38 (60.53%) 2/15 (13.33%) 0.005 * no worsening of uveitis at each visit 42/44 (95.45%) 15/15 (100%) 0.999 prednisone dose ≤ 0.1mg/kg/day at 6-month follow-up visit 13/16 (81.25%) 2/7 (28.57%) 0.026 * Treatment success 41/44 (93.18%) 3/15 (20%) < 0.001 * Abbreviation: BCVA, best-corrected visual acuity; ACC, Anterior chamber cell; VH, Vitreous haze; FA, fluorescein angiography. * p < 0.05 NAAU vs. AAU Discussion In present study, we classified 59 pediatric patients with uveitis undergoing ADA treatment into AAU and NAAU groups according to the presence of anterior segment inflammation, deviating from the routine SUN criteria that typically rely on the anatomic location of the inflammation [ 16 ]. The AAU group included cases with anterior, panuveitis, and anterior and intermediate uveitis that encompassed inflammation in both the anterior chamber and vitreous, aligning with SUN definitions. In contrast, the NAAU group included cases of posterior and intermediate uveitis without concurrent inflammation in the anterior chamber. Our findings demonstrated significant improvements in BCVA, ACC, VH, RNFL thickness, FA scores in the AAU group treated with ADA from baseline to the 6-month follow-up visit. However, these improvements were not observed in the NAAU group, except for ACC. The results suggested that ADA treatment was more likely to be effective in AAU, but may be less effective in patients with NAAU. Although the systemic IMT and glucocorticoid dosing showed a reduction in both the AAU and NAAU groups during the same period, a higher proportion of patients on less than 0.1 mg/kg/day of prednisone at the 6-month follow-up visit were observed in the AAU group compared to the NAAU group. In fact, we reduced the systemic glucocorticoid dosing in patients with NAAU who respond poorly to treatment, given concerns about growth retardation in children. The rate of treatment success was significantly higher in the AAU group than in the NAAU group (93.18% vs 20%), highlighting superior efficacy of ADA in treating noninfectious pediatric uveitis with apparent anterior chamber inflammation. While existing studies generally support ADA as a treatment for various types of pediatric non-infectious uveitis, particularly JIA-associated uveitis, they often lack an examination of the correlation between the clinical characteristics of uveitis and the success rate of ADA treatment. Most reported that most cases of pediatric noninfectious uveitis are idiopathic, with anterior uveitis being the most common manifestation (39.2%-78.0% of all cases). Intermediate, posterior, and panuveitis have more variable distributions, accounting for 0.0–33.3%, 4.0–58.7%, and 1.0–31.0% of cases, respectively. The profile of our included cases aligns with these reports [ 19 ]. The possible diverse etiology of idiopathic uveitis and the varied anatomic localization of uveitis suggested different responses to ADA treatment. Identifying cases that respond well to ADA is essential. The results of this present study provide evidence for the selection of ADA for the treatment of pediatric noninfectious uveitis based on clinical characteristic, particularly apparent anterior chamber inflammation. In this study, we used the RNFL thickness as a parameter to evaluate inflammation. Lee et al. and Shulman et al. reported that the average RNFL thickness significantly increased in the eyes with acute anterior uveitis during active phase compared to the inactive phase or healthy fellow eye, suggesting that RNFL thickness may be useful in assessing disease activity [ 20 ] [ 21 ]. The intermediate- and pan-uveitis have a higher probability of having increased RNFL thickness than does anterior uveitis, possibly because the primary inflammation site is closer to the optic disc [ 22 ]. Currently, spectral domain-optical OCT is a noninvasive retinal imaging technology that allows accurate measurement of retinal layer thickness. Almost all pediatric patients with uveitis can smoothly undergo OCT examination, not like FA, which is particularly challenging to perform in young children, as it is relatively invasive. Cho et al. showed that SD-OCT assessment of RNFL thickness is reproducible and correlates with the presence vs. resolution of uveitis [ 23 ]. Due to the low incidence of macular cystoid edema in children with non-infectious uveitis (six out of 59 cases in our study), we did not use macular thickness as a parameter. In the AAU group, 3 patients did not respond to ADA treatment. Among them, two had a disease course of more than 2 years, suggesting that severe ocular tissue damage due to long-term inflammation might hinder functional recovery. It is speculated that initiating ADA treatment early in the disease course may still offer a possibility of effectiveness. The third unresponsive patient had VKH disease in the chronic/recurrent anterior uveitis stage without evident choroiditis, suggesting that ADA may not be suitable for the treatment of simple chronic/recurrent anterior uveitis in VKH. The failure rate of ADA treatment in the NAAU group was 80%, though there were still 3 patients who did respond to ADA therapy. These 3 patients presented with extensive retinal vascular leakage in FA, resembling the angiographic presentation of Behcet's retinal vasculitis. Despite lacking other symptoms of Behcet's disease and awaiting a definitive diagnosis, it cannot be ruled out that anterior uveitis may have occurred in these cases if ADA treatment had not been initiated. Several studies have reported the response rates of ADA in the treatment of pediatric noninfectious uveitis ranging from 58.8–95.5% [ 6 , 12 – 15 ]. Specifically, Ucan et al. [ 15 ], Deitch et al. [ 13 ], and Al-Julandani et al. [ 6 ] reported response rate of 58.8%, 66.7% and 81.25%, respectively, which were lower than the response rate observed in our AAU group. This difference may be due to the fact that our study focused on patients with apparent anterior chamber inflammation, resulting in a higher response rate to ADA. In contrast, these studies may have included cases of partial uveitis without anterior chamber inflammation, resulting in a decreased response rate. Another contributing factor may be that their studies primarily involved refractory cases in children who had failed traditional immunosuppressive therapy before initiating ADA. In our study, about half of the children were treated with ADA in combination with traditional immunosuppressant therapy as first-line systemic therapy. Choe et al. [ 14 ] and Kouwenberg et al. [ 12 ] reported treatment response rates as high as 95.5% and 91% respectively, which aligns with our findings. The former study included only cases of anterior and panuveitis with apparent anterior chamber inflammation. The latter study included anterior uveitis, intermediate uveitis and panuveitis, without posterior uveitis. This study did not specify whether the included cases of intermediate uveitis had apparent anterior chamber inflammation. If apparent anterior chamber inflammation were present in these cases, the higher treatment response rate would be consistent with our results. Pediatric anterior uveitis is often associated with peripheral retinal vascular inflammation which can be assessed by fluorescein vascular leakage. This association may explain why pediatric anterior uveitis tends to be more chronic than its adult counterpart, necessitating more active systemic treatment. Our findings align with this observation, demonstrating that ADA can alleviate retinal vascular leakage in AAU. This finding is consistent with the study conducted by Song et al.[ 24 ] which demonstrated that ADA effectively alleviated peripheral vascular leakage in pediatric patients with chronic anterior uveitis, thereby better controlling anterior chamber inflammation. This is the first study to provide evidence for the selection of ADA for the treatment of pediatric noninfectious uveitis based on clinical characteristics, particularly anterior chamber inflammation. The limitations of this study should be acknowledged, including its retrospective design, a relatively small patient cohort in the NAAU group, variability in the follow-up schedule and use of the RNFL thickness as a parameter to evaluate inflammation. Prospective studies with larger sample sizes should be performed to further elucidate the treatment efficacy of ADA on pediatric non-infectious uveitis with NAAU. Glaucoma is a major confounding factor when using RNFL thickness to evaluate inflammation. However, we included children with elevated intraocular pressure in the analysis because their elevated intraocular pressure was promptly controlled by IOP-lowering eye drops. During follow-up, IOP-lowering medications were discontinued in all children due to the efficacy of ADA, which significantly reduced the need for topical and systemic glucocorticoids. In the NAAU group, none of the children developed elevated IOP during ADA treatment. Conclusion This study provides valuable real-world clinical data which suggests that ADA is more effective in the pediatric non-infectious uveitis with AAU than with NAAU, suggesting that ADA may be the preferred treatment option for pediatric non-infectious uveitis presenting with AAU. Abbreviations ADA Adalimumab AAU apparent anterior uveitis NAAU non-apparent anterior uveitis RNFL retinal nerve fiber layer BCVA best-corrected visual acuity FA fluorescein angiography VH vitreous haze IMT immunosuppression therapy TNF-α tumor necrosis factor alpha OCT optical coherence tomography IOP intraocular pressure SUN Standardization of Uveitis Nomenclature Declarations Acknowledgments We greatly appreciate all participants in the study. Author contributions YC, and CZ conceived the study; XX and YZ followed up and collected data; QL and JX analyzed the data; YC, CZ, and XX wrote the manuscript. All authors contributed to the article and approved the submitted version. Funding This work was supported by the Key Research and Development plan of Shaanxi Province [grant number 2022SF-366]. Data availability statement The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author. Ethics statement and consent to participate This protocol was approved by the Ethics Committee of Xi'an People's Hospital (Xi’an Fourth Hospital) (No.20220023), which was conducted in accordance with the Declaration of Helsinki. Competing interests The authors declare that they have no competing interests. Consent to publish Not applicable. References Maleki A, Anesi SD, Look-Why S, Manhapra A, Foster CS. Pediatric uveitis: A comprehensive review. SURV OPHTHALMOL. 2022;67(2):510–29. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. AM J OPHTHALMOL. 2000;130(4):492–513. Quartier P, Baptiste A, Despert V, Allain-Launay E, Kone-Paut I, Belot A, Kodjikian L, Monnet D, Weber M, Elie C, et al. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. ANN RHEUM DIS. 2018;77(7):1003–11. Sonmez HK, Evereklioglu C, Gulmez SD. Prompt and Sustained Suppression of Intraocular Inflammation with Adalimumab in Pediatric Patients with Non-Infectious Uveitis Resistant to Traditional Managements: A 6-Month Follow-Up Research. OCUL IMMUNOL INFLAMM. 2023;31(10):1992–96. Vitale A, Casa FD, Guerriero S, Ragab G, Mauro A, Caggiano V, Cattalini M, Del GE, Favale R, Gaggiano C, et al. Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry. OPHTHALMOL THER. 2023;12(4):1957–71. Al-Julandani DA, Bagri NK, Tsang N, Clarke S, Upadhyay A, Guly C, Ramanan AV. Outcome of adalimumab monotherapy in paediatric non-infectious uveitis. PEDIATR RHEUMATOL. 2023;21(1):21. Suhler EB, Adan A, Brezin AP, Fortin E, Goto H, Jaffe GJ, Kaburaki T, Kramer M, Lim LL, Muccioli C, et al. Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III. Ophthalmology. 2018;125(7):1075–87. Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016;388(10050):1183–92. Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, et al. Adalimumab in Patients with Active Noninfectious Uveitis. NEW ENGL J MED. 2016;375(10):932–43. Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, Hardwick B, Hickey H, Hughes D, Woo P, et al. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. NEW ENGL J MED. 2017;376(17):1637–46. Angeles-Han ST, Lo MS, Henderson LA, Lerman MA, Abramson L, Cooper AM, Parsa MF, Zemel LS, Ronis T, Beukelman T, et al. Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Juvenile Idiopathic Arthritis-Associated and Idiopathic Chronic Anterior Uveitis. ARTHRIT CARE RES. 2019;71(4):482–91. Kouwenberg CV, Koopman-Kalinina AV, de Boer JH. Clinical benefits and potential risks of adalimumab in non-JIA chronic paediatric uveitis. ACTA OPHTHALMOL. 2022;100(4):e994–1001. Deitch I, Amer R, Tomkins-Netzer O, Habot-Wilner Z, Friling R, Neumann R, Kramer M. The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies. GRAEF ARCH CLIN EXP. 2018;256(4):801–08. Choe S, Heo JW, Oh BL. Quiescence and Subsequent Anterior Chamber Inflammation in Adalimumab-treated Pediatric Noninfectious Uveitis. Korean J Ophthalmol. 2020;34(4):274–80. Ucan GG, Yalcinbayir O, Cekic S, Yildiz M, Kilic SS. Anti-Tumor Necrosis Factor Treatment in the Management of Pediatric Noninfectious Uveitis: Infliximab Versus Adalimumab. J OCUL PHARMACOL TH. 2021;37(4):236–40. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. AM J OPHTHALMOL. 2005; 140(3):509 – 16. Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467–71. Nussenblatt RB, Peterson JS, Foster CS, Rao NA, See RF, Letko E, Buggage RR. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005;112(5):764–70. LaMattina KC, Koreishi AF. What is new in paediatric uveitis? CURR OPIN OPHTHALMOL. 2018;29(5):412–18. Lee MW, Lee TH, Won YK, Shin YI, Kim JY. Characteristics of retinal layer thickness in acute anterior uveitis: an optical coherence tomography study. ACTA OPHTHALMOL. 2020;98(1):e50–55. Shulman S, Goldenberg D, Habot-Wilner Z, Goldstein M, Neudorfer M. Optical coherence tomography characteristics of eyes with acute anterior uveitis. ISR MED ASSOC J. 2012;14(9):543–46. Kouwenberg CV, Blom LA, Vellinga SC, Bozkir I, de Boer JH, Ayuso VK. The Role of the Retinal Nerve Fiber Layer Thickness on OCT in the Evaluation of Papillitis in Childhood Uveitis. AM J OPHTHALMOL. 2023;254:62–8. Cho H, Pillai P, Nicholson L, Sobrin L. Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring. OCUL IMMUNOL INFLAMM. 2016;24(2):194–206. Song H, Zhao C, Xiao J, Gao F, Li D, Zhang M. The Efficacy and Safety of Adalimumab in Treating Pediatric Noninfectious Chronic Anterior Uveitis With Peripheral Retinal Vascular Leakage: A Pilot Study. FRONT MED-LAUSANNE. 2022;9:813696. Additional Declarations No competing interests reported. Supplementary Files supplentaryinformation.docx Cite Share Download PDF Status: Published Journal Publication published 13 Jan, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 10 Jun, 2024 Editor assigned by journal 08 Jun, 2024 Submission checks completed at journal 08 Jun, 2024 First submitted to journal 06 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4540347","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312575137,"identity":"29e3b6ca-b436-408d-8f2e-ef375d0e8161","order_by":0,"name":"Chunbo Zhang","email":"","orcid":"","institution":"Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":false,"prefix":"","firstName":"Chunbo","middleName":"","lastName":"Zhang","suffix":""},{"id":312575138,"identity":"f24636be-9447-4734-9921-8dfeebcb1a15","order_by":1,"name":"Xiaorong Xue","email":"","orcid":"","institution":"Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":false,"prefix":"","firstName":"Xiaorong","middleName":"","lastName":"Xue","suffix":""},{"id":312575139,"identity":"58cc0009-10c3-482d-b146-fc9948100b17","order_by":2,"name":"Jinan Xiao","email":"","orcid":"","institution":"Shaanxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":false,"prefix":"","firstName":"Jinan","middleName":"","lastName":"Xiao","suffix":""},{"id":312575140,"identity":"899f8c88-f6cf-4387-bed5-1e7040ff7acd","order_by":3,"name":"Qiongge Li","email":"","orcid":"","institution":"Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":false,"prefix":"","firstName":"Qiongge","middleName":"","lastName":"Li","suffix":""},{"id":312575141,"identity":"d400d985-5d67-4804-8384-6c969c533566","order_by":4,"name":"Yuyao Zhai","email":"","orcid":"","institution":"Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":false,"prefix":"","firstName":"Yuyao","middleName":"","lastName":"Zhai","suffix":""},{"id":312575142,"identity":"d590b572-35bf-401c-b48c-67d175835ec5","order_by":5,"name":"Ying Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACCRBhwMDAz8zY+CChwoYELZLtzM0GD86kEasFpOs8e5vkw7ZDhHXwz24+9pin4I7dzGbGtooEtgMM/O3dCfgtuXMs3ZjH4FlyPzNj240EnjsMEmfObsCrxUAix0yax+BwsmQzSIvEM6BILiEt+d/AWgwOM7YVJBgcJkZLDhtIix1IC0NCAhFaJG6kmUnOMTicAHRYs0TCgTQegn7hn5H8TOLNn8P2/PzHH378+c9Gjr+9F78WEGDiYWBIbIByeAgqBwHGHwwM9kSpHAWjYBSMgpEJAEXKSSyToa8mAAAAAElFTkSuQmCC","orcid":"","institution":"Shaanxi Eye Hospital, Xi’an People’s Hospital (Xi’an Fourth Hospital), Affiliated People’s Hospital of Northwest University","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-06-06 12:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4540347/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4540347/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-025-03859-6","type":"published","date":"2025-01-13T15:57:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74284670,"identity":"146af4d1-2450-4909-943c-62480909ea88","added_by":"auto","created_at":"2025-01-20 16:10:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":621620,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4540347/v1/84d6d8b9-2210-457c-8754-4bc33e9558d4.pdf"},{"id":58964721,"identity":"a96537c4-9018-498f-b48d-5f38f4521807","added_by":"auto","created_at":"2024-06-24 17:51:14","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12268,"visible":true,"origin":"","legend":"","description":"","filename":"supplentaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4540347/v1/9de78af7bc02f6aa22e9d7e5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Adalimumab in pediatric non-infectious uveitis with apparent and non-apparent anterior uveitis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePediatric non-infectious uveitis is characterized by the persistence or recurrence of intraocular inflammation, posing a substantial risk of visual impairment in approximately one-third of affected individuals [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The management of most cases of pediatric non-infectious uveitis necessitates a systemic and prolonged treatment regimen, typically following a stepwise approach. Systemic glucocorticoids use in children and adolescents raises significant concerns due to growth retardation and other metabolic or endocrine side effects. Consequently, the overarching objective of long-term therapy is to achieve corticosteroid-free remission through the implementation of corticosteroid-sparing immunomodulatory agents for the management of chronic or recurrent pediatric uveitis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConventional corticosteroid-sparing immunomodulatory agents include methotrexate (MTX), azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus and cyclosporine (CsA) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite the efficacy of these agents, a subset of patients remains refractory, exhibiting inadequate response to conventional immunosuppressants. In such instances, the therapeutic paradigm advances to include biologic agents, among which tumor necrosis factor alpha (TNF-α) inhibitors stand out as pivotal contributors to the evolving landscape of pediatric uveitis treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdalimumab (ADA), a fully humanized anti-TNF-α monoclonal antibody, has been recognized as a promising agent for treating noninfectious uveitis in adults and children [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, the SYCAMORE study, a randomized, double blinded, placebo-controlled study, provided compelling evidence that the combination of ADA with MTX yielded a lower rate of treatment failure compared to MTX alone for treating juvenile idiopathic arthritis (JIA)-associated uveitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, ADA was efficacious in managing non-JIA chronic uveitis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Despite these advancements, a subset of pediatric patients with uveitis within our clinical practice exhibit insufficient or no response to TNF-α inhibitor treatment.\u003c/p\u003e \u003cp\u003eOther studies reported that pediatric uveitis cases of varied etiologies showed response rates ranging from 58.8\u0026ndash;95.5% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The substantial disparity in treatment success rates across different studies prompts a crucial inquiry into the identification of clinical features closely associated with the responsiveness to ADA treatment. Within this context, our clinical observations lead us to postulate that pediatric patients with non-infectious uveitis, specifically those presenting with apparent anterior uveitis (AAU), may have a more favorable response to ADA treatment than those with non-apparent anterior uveitis (NAAU) during the early stages of clinical intervention. Consequently, we conducted a retrospective analysis to systematically compare the efficacy of ADA treatment between these two groups at both baseline and the 6-month follow-up visit.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eStudy Design and Patient Identification\u003c/p\u003e \u003cp\u003eThis retrospective study was conducted at a tertiary ophthalmic center in Shaanxi, China. Medical records of pediatric patients (age\u0026thinsp;\u0026le;\u0026thinsp;16 years) with uveitis who visited the uveitis service of the ophthalmology department at Xi\u0026rsquo;an People\u0026rsquo;s Hospital (Xi\u0026rsquo;an Fourth Hospital) (Shannxi, China) between January 2021 and February 2023 were reviewed. The inclusion criteria were: a confirmed diagnosis of non-infectious chronic uveitis and treatment with ADA (Humira; AbbVie Inc., Ludwigshafen, Germany) or ADA biosimilars (Anjianning; BioRay Pharmaceutical Co., Ltd., Taizhou, Zhejiang province, CHN or QLETLI; Bio-Thera Solutions Ltd., Guangzhou, Guangdong province, CHN) for a duration exceeding 6 months. The initial dosage regimen consisted of 80 mg, followed by 40 mg after 1 week. Subsequently, a maintenance dose of 40 mg was administered every 2 weeks, while those weighing ˂30 kg received half the standard dose. Exclusion criteria comprised the presence of corneal or lens opacity hindering the visualization of the anterior chamber or fundus, or impeding optimal imaging using spectral-domain optical coherence tomography (OCT) devices. The anatomical classification of uveitis was determined according to the Standardization of Uveitis Nomenclature (SUN) Working Group [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe included patients were stratified into two groups: the apparent anterior uveitis (AAU) group and the non-apparent anterior uveitis (NAAU) group. Criteria for inclusion in the AAU group were patients exhibiting ACC grade\u0026thinsp;\u0026ge;\u0026thinsp;1\u0026thinsp;+\u0026thinsp;at least one visit before initiation of ADA treatment, pupillary adhesion or band degeneration of the cornea. Inclusion in the NAAU group required patients to display an ACC grade\u0026thinsp;\u0026le;\u0026thinsp;0.5\u0026thinsp;+\u0026thinsp;during all visits, and the absence of pupillary adhesion and band degeneration of the cornea.\u003c/p\u003e \u003cp\u003e This study protocol underwent rigorous evaluation by the Ethics Committee of Xi'an People's Hospital (Xi\u0026rsquo;an Fourth Hospital) (No.20220023). Considering the retrospective nature of this study, the requirement for informed consent was waived by the Ethics Committee. The study was done in compliance with the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eData Collection\u003c/p\u003e \u003cp\u003eA comprehensive dataset of demographic and clinical characteristics was assembled, including gender, age, anatomical uveitis classification, uveitis etiology and ocular complication at the baseline visit. A thorough ophthalmic examination, such as best corrected visual acuity (BCVA) through a logarithmic visual acuity chart, intraocular pressure (IOP), slit-lamp examination of the anterior segment, and a detailed examination of the dilated vitreous and fundus, were performed at both baseline and follow-up visits. The use of concurrent systemic glucocorticoids and/or other immunosuppressive therapy were documented. Patients were scheduled for follow-up assessments based on their specific conditions between the baseline and 6-month follow-up visit.\u003c/p\u003e \u003cp\u003eGrading of anterior chamber cell (ACC) count was executed in adherence to the SUN Working Group criteria [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Vitreous haze (VH) was evaluated by the Nussenblatt scale [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Retinal nerve fiber layer (RNFL) thickness measurements were obtained through optical coherence tomography (OCT) (Spectralis, Heidelberg Engineering, Germany). Assessment of retinal vascular leakage was evaluated by fluorescein angiography (FA) (Heidelberg Engineering, Germany). FA scores were independently evaluated by two ophthalmologists (Y.C. and J.-A.X.) based on the scoring system established by the Angiography Scoring for Uveitis Working Group (ASUWOG) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The systemic immunosuppression therapy (IMT) load and glucocorticoid load were assessed utilizing a weighted semiquantitative scale for each prescribed medication as detailed in supplementary Table\u0026nbsp;1 to present a consolidated, single numeric score reflecting the overall immunosuppression load per unit body weight per day [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe improvement of outcomes was defined as follows: visual acuity increased by two or more lines; ACC or VH reduced two or more grades or to grade 0. The worsening of outcomes was defined as follows: visual acuity decreased by two or more lines; ACC or VH increased by two or more grades or to grade 4; The improvement or worsening of retinal vascular leakage detected by FA was assessed by two experienced ophthalmologists (YC and JA-X). Treatment success of uveitis was defined as the improvement of any one of the specified outcomes at the 6-month follow-up visit compared to the baseline visit in the eye exhibiting more severe intraocular inflammation, with no worsening of any outcome observed during the 6-month follow-up in the both eyes, and the prednisone dose reduced to \u0026le;\u0026thinsp;0.1 mg/kg/day at the 6-month follow-up visit.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were used to report the demographic and clinical features of the patients. Demographics, clinical characteristics, the improvement of outcome variables and the rate of treatment success between the two groups were compared using the Wilcoxon rank sum test, Pearson's Chi-squared test, or Fisher's exact test, as appropriate. The outcome variables were evaluated using a mixed model for repeated measures (MMRM) and reported as the difference of marginal means of the two time point of measurement (baseline and month six) for both AAU and NAAU patients. The model included the paired eyes (left and right in same individual) and time point of measurement (baseline and 6-month follow-up visit) as fixed effects. Patient-specific effects enter the model as a random effect with normal distribution and an expected value of zero. The analysis was performed using the R statistical software version 4.3.2 (R Project for Statistical Computing). A significance level of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered indicative of a statistically significant difference.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this retrospective and nonrandomized study, we initially screened 68 consecutive pediatric patients with NIU who underwent ADA treatment. Four patients were lost to follow-up within the initial 6 months of ADA initiation. Two patients were unable to cooperate with the examination due to their young age, while two patients presented with heavy cataracts, and one patient exhibited severe corneal band degeneration, resulting in poor OCT image quality. These nine patients were excluded from the study, leaving 59 patients for analysis. Among the included patients, 44(83 eyes) were categorized into the AAU group (74.58%), and the remaining 15 (28 eyes) formed the NAAU group (25.42%). Baseline characteristics of the patients when ADA was initiated are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics of the Patients When ADA Was Initiated.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAAU\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNAAU\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients/eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.30(7.10,12.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.60(7.95,13.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male/female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(26/18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(6/9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (\u0026lt;\u0026thinsp;30 kg /\u0026gt;30kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.738\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral/unilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eEtiology of uveitis [No. (%)]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVogt\u0026ndash;Koyanagi\u0026ndash;Harada disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(6.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJuvenile idiopathic arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(9.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeh\u0026ccedil;et\u0026rsquo;s disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(6.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIdiopathic uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(77.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAnatomic types of uveitis [No. (%)]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnterior uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(65.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntermediate (+\u0026thinsp;anterior) uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(15.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntermediate (- anterior) uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior uveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePanuveitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(18.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications [eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(48.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(25.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCataract [eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(34.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(25.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular hypertension [eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(8.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePupillary adhesion [eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(34.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBand degeneration of cornea\u0026nbsp;[eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(18.07%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emacular cystoid edema [eye. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(9.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration before ADA treatment (months), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.50(3.00, 11.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00(3.50, 12.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic IMT therapy before baseline [No. (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (52.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (66.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.332\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u0026thinsp;+\u0026thinsp;methotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (13.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (26.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u0026thinsp;+\u0026thinsp;cyclosporin A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.447\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u0026thinsp;+\u0026thinsp;azathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.447\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u0026thinsp;+\u0026thinsp;cyclosporin A\u0026thinsp;+\u0026thinsp;azathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclosporin A\u0026thinsp;+\u0026thinsp;methotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (9.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e*\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 NAAU vs. AAU\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn AAU group, the BCVA showed a statistically significant improvement at the 6-month follow-up visit [-0.12, 95% CI (-0.15\u0026ndash; -0.09), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. Similarly, RNFL thickness exhibited a significant decrease [-17.00, 95% CI (-19.68\u0026ndash; -14.32), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. Thirty-eight patients (86.36%) had undergone FA at baseline and at the 6-month follow-up visit. The improvements in FA scores were attributed primarily to capillary leakage reduction, and were significant [-4.82, 95% CI (-5.45\u0026ndash; -4.19), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. ACC [-2.73, 95%CI (-2.98\u0026ndash; -2.49), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] and VH [-0.34, 95%CI (-0.45\u0026ndash; -0.24), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] also showed significant improvement from baseline to the 6-month follow-up visit (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In contrast, the NAAU group exhibited no significant differences in BCVA [-0.02, 95% CI (-0.06\u0026ndash;0.02), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.382], RNFL thickness [-3.25, 95% CI (-6.72\u0026ndash;0.22), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.066], FA scores [-0.29, 95% CI (-1.36\u0026ndash;0.78), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.592] and VH [-0.04, 95%CI (-0.18\u0026ndash;0.11), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.620] (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) between the baseline and 6-month follow-up visit. Reductions were noted in systemic IMT and glucocorticoid dosing comparing baseline to the 6-month follow-up visit in both the AAU [-3.59, 95% CI (-4.66\u0026ndash; -2.52), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], [-1.50, 95% CI (-2.20\u0026ndash; -0.80), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001] (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and NAAU [-1.13, 95% CI (-2.11\u0026ndash; -0.15), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026], [-0.87, 95% CI (-1.49\u0026ndash; -0.24), \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010] groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcome Variables of 44 Patients (83 Eyes) in AAU Group at baseline and at 6-month Follow-up Visit.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDifference, (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003emean (95CI%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients/eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44/83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44/83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elogMAR BCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.18 (0.13\u0026ndash;0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06 (0.01\u0026ndash;0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.12 (-0.15\u0026ndash; -0.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRNFL(\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134.36 (130.83\u0026ndash;137.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117.36 (113.83\u0026ndash;120.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-17.00 (-19.68\u0026ndash; -14.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA score\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.09 (6.58\u0026ndash;9.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.27 (1.76\u0026ndash;4.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4.82 (-5.45\u0026ndash; -4.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.00 (2.77\u0026ndash;3.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.26 (0.04\u0026ndash;0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.73 (-2.98\u0026ndash; -2.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.47 (0.34\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13 (-0.01\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.34 (-0.45\u0026ndash; -0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMT load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.91 (7.13\u0026ndash;8.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.32 (3.54\u0026ndash;5.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.59 (-4.66\u0026ndash; -2.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.80 (1.21\u0026ndash;2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30 (-0.29\u0026ndash;0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.50 (-2.20\u0026ndash; -0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviation: BCVA, best-corrected visual acuity; RNFL, Retinal nerve fiber layer thickness; FA, fluorescein angiography; IMT, immunosuppression therapy; CI, confidence interval. *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, 6-month follow-up visit vs. baseline; \u003csup\u003e#\u003c/sup\u003en\u0026thinsp;=\u0026thinsp;72\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcome Variables of 15 Patiens (28 Eyes) in NAAU Group at Baseline and 6-month Follow-up Visit.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDifference (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003emean (95CI%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients/eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elogMAR BCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.26 (0.09\u0026ndash;0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25 (0.07\u0026ndash;0.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.02 (-0.06\u0026ndash;0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRNFL(\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.10 (119.48\u0026ndash;128.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120.85 (116.23\u0026ndash;125.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.25 (-6.72\u0026ndash;0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.39 (7.07\u0026ndash;9.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.11 (6.78\u0026ndash;9.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.29 (-1.36\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.592\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.45 (0.22\u0026ndash;0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41 (0.19\u0026ndash;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.04 (-0.18\u0026ndash;0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMT load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.60 (6.23\u0026ndash;8.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.47 (5.09\u0026ndash;7.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.13 (-2.11 \u0026ndash; -0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoid load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.67 (0.69\u0026ndash;2.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.80 (-0.18\u0026ndash;1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.87 (-1.49 \u0026ndash; -0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviation: BCVA, best-corrected visual acuity; RNFL, Retinal nerve fiber layer thickness; FA, fluorescein angiography; IMT load, immunosuppression therapy load; CI, confidence interval. *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 6-month follow-up visit vs. baseline\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on our defined criteria for the improvement of outcome variables, the improvement rates of VH, RNFL thickness and FA scores in the AAU group were significantly higher compared to those in the NAAU group. In addition, a higher proportion of patients in the AAU group were able to reduce prednisone dosage to less than 0.1 mg/kg/day compared to the NAAU group. The composite result showed that the treatment success rate of uveitis in the AAU group was substantially higher than that in the NAAU group (93.18% vs 20%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Improvement of Outcome Variables and The Rate of Treatment Success After ADA Treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAAU (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNAAU (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/ 44 (29.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 /15 (6.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39/44 (88.84%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/25 (68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/11 (18.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 /38 (60.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/15 (13.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno worsening of uveitis at each visit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42/44 (95.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/15 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprednisone dose\u0026thinsp;\u0026le;\u0026thinsp;0.1mg/kg/day at 6-month follow-up visit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/16 (81.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/7 (28.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.026\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41/44 (93.18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/15 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviation: BCVA, best-corrected visual acuity; ACC, Anterior chamber cell; VH, Vitreous haze; FA, fluorescein angiography. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 NAAU vs. AAU\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn present study, we classified 59 pediatric patients with uveitis undergoing ADA treatment into AAU and NAAU groups according to the presence of anterior segment inflammation, deviating from the routine SUN criteria that typically rely on the anatomic location of the inflammation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The AAU group included cases with anterior, panuveitis, and anterior and intermediate uveitis that encompassed inflammation in both the anterior chamber and vitreous, aligning with SUN definitions. In contrast, the NAAU group included cases of posterior and intermediate uveitis without concurrent inflammation in the anterior chamber. Our findings demonstrated significant improvements in BCVA, ACC, VH, RNFL thickness, FA scores in the AAU group treated with ADA from baseline to the 6-month follow-up visit. However, these improvements were not observed in the NAAU group, except for ACC. The results suggested that ADA treatment was more likely to be effective in AAU, but may be less effective in patients with NAAU. Although the systemic IMT and glucocorticoid dosing showed a reduction in both the AAU and NAAU groups during the same period, a higher proportion of patients on less than 0.1 mg/kg/day of prednisone at the 6-month follow-up visit were observed in the AAU group compared to the NAAU group. In fact, we reduced the systemic glucocorticoid dosing in patients with NAAU who respond poorly to treatment, given concerns about growth retardation in children. The rate of treatment success was significantly higher in the AAU group than in the NAAU group (93.18% vs 20%), highlighting superior efficacy of ADA in treating noninfectious pediatric uveitis with apparent anterior chamber inflammation. While existing studies generally support ADA as a treatment for various types of pediatric non-infectious uveitis, particularly JIA-associated uveitis, they often lack an examination of the correlation between the clinical characteristics of uveitis and the success rate of ADA treatment. Most reported that most cases of pediatric noninfectious uveitis are idiopathic, with anterior uveitis being the most common manifestation (39.2%-78.0% of all cases). Intermediate, posterior, and panuveitis have more variable distributions, accounting for 0.0\u0026ndash;33.3%, 4.0\u0026ndash;58.7%, and 1.0\u0026ndash;31.0% of cases, respectively. The profile of our included cases aligns with these reports [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The possible diverse etiology of idiopathic uveitis and the varied anatomic localization of uveitis suggested different responses to ADA treatment. Identifying cases that respond well to ADA is essential. The results of this present study provide evidence for the selection of ADA for the treatment of pediatric noninfectious uveitis based on clinical characteristic, particularly apparent anterior chamber inflammation.\u003c/p\u003e \u003cp\u003eIn this study, we used the RNFL thickness as a parameter to evaluate inflammation. Lee et al. and Shulman et al. reported that the average RNFL thickness significantly increased in the eyes with acute anterior uveitis during active phase compared to the inactive phase or healthy fellow eye, suggesting that RNFL thickness may be useful in assessing disease activity [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The intermediate- and pan-uveitis have a higher probability of having increased RNFL thickness than does anterior uveitis, possibly because the primary inflammation site is closer to the optic disc [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Currently, spectral domain-optical OCT is a noninvasive retinal imaging technology that allows accurate measurement of retinal layer thickness. Almost all pediatric patients with uveitis can smoothly undergo OCT examination, not like FA, which is particularly challenging to perform in young children, as it is relatively invasive. Cho et al. showed that SD-OCT assessment of RNFL thickness is reproducible and correlates with the presence vs. resolution of uveitis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Due to the low incidence of macular cystoid edema in children with non-infectious uveitis (six out of 59 cases in our study), we did not use macular thickness as a parameter.\u003c/p\u003e \u003cp\u003eIn the AAU group, 3 patients did not respond to ADA treatment. Among them, two had a disease course of more than 2 years, suggesting that severe ocular tissue damage due to long-term inflammation might hinder functional recovery. It is speculated that initiating ADA treatment early in the disease course may still offer a possibility of effectiveness. The third unresponsive patient had VKH disease in the chronic/recurrent anterior uveitis stage without evident choroiditis, suggesting that ADA may not be suitable for the treatment of simple chronic/recurrent anterior uveitis in VKH. The failure rate of ADA treatment in the NAAU group was 80%, though there were still 3 patients who did respond to ADA therapy. These 3 patients presented with extensive retinal vascular leakage in FA, resembling the angiographic presentation of Behcet's retinal vasculitis. Despite lacking other symptoms of Behcet's disease and awaiting a definitive diagnosis, it cannot be ruled out that anterior uveitis may have occurred in these cases if ADA treatment had not been initiated.\u003c/p\u003e \u003cp\u003eSeveral studies have reported the response rates of ADA in the treatment of pediatric noninfectious uveitis ranging from 58.8\u0026ndash;95.5% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Specifically, Ucan et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], Deitch et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and Al-Julandani et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] reported response rate of 58.8%, 66.7% and 81.25%, respectively, which were lower than the response rate observed in our AAU group. This difference may be due to the fact that our study focused on patients with apparent anterior chamber inflammation, resulting in a higher response rate to ADA. In contrast, these studies may have included cases of partial uveitis without anterior chamber inflammation, resulting in a decreased response rate. Another contributing factor may be that their studies primarily involved refractory cases in children who had failed traditional immunosuppressive therapy before initiating ADA. In our study, about half of the children were treated with ADA in combination with traditional immunosuppressant therapy as first-line systemic therapy. Choe et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Kouwenberg et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] reported treatment response rates as high as 95.5% and 91% respectively, which aligns with our findings. The former study included only cases of anterior and panuveitis with apparent anterior chamber inflammation. The latter study included anterior uveitis, intermediate uveitis and panuveitis, without posterior uveitis. This study did not specify whether the included cases of intermediate uveitis had apparent anterior chamber inflammation. If apparent anterior chamber inflammation were present in these cases, the higher treatment response rate would be consistent with our results.\u003c/p\u003e \u003cp\u003ePediatric anterior uveitis is often associated with peripheral retinal vascular inflammation which can be assessed by fluorescein vascular leakage. This association may explain why pediatric anterior uveitis tends to be more chronic than its adult counterpart, necessitating more active systemic treatment. Our findings align with this observation, demonstrating that ADA can alleviate retinal vascular leakage in AAU. This finding is consistent with the study conducted by Song et al.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] which demonstrated that ADA effectively alleviated peripheral vascular leakage in pediatric patients with chronic anterior uveitis, thereby better controlling anterior chamber inflammation.\u003c/p\u003e \u003cp\u003eThis is the first study to provide evidence for the selection of ADA for the treatment of pediatric noninfectious uveitis based on clinical characteristics, particularly anterior chamber inflammation. The limitations of this study should be acknowledged, including its retrospective design, a relatively small patient cohort in the NAAU group, variability in the follow-up schedule and use of the RNFL thickness as a parameter to evaluate inflammation. Prospective studies with larger sample sizes should be performed to further elucidate the treatment efficacy of ADA on pediatric non-infectious uveitis with NAAU. Glaucoma is a major confounding factor when using RNFL thickness to evaluate inflammation. However, we included children with elevated intraocular pressure in the analysis because their elevated intraocular pressure was promptly controlled by IOP-lowering eye drops. During follow-up, IOP-lowering medications were discontinued in all children due to the efficacy of ADA, which significantly reduced the need for topical and systemic glucocorticoids. In the NAAU group, none of the children developed elevated IOP during ADA treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides valuable real-world clinical data which suggests that ADA is more effective in the pediatric non-infectious uveitis with AAU than with NAAU, suggesting that ADA may be the preferred treatment option for pediatric non-infectious uveitis presenting with AAU.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADA \u0026nbsp; \u0026nbsp;Adalimumab\u003c/p\u003e\n\u003cp\u003eAAU \u0026nbsp; \u0026nbsp;apparent anterior uveitis\u003c/p\u003e\n\u003cp\u003eNAAU \u0026nbsp;non-apparent anterior uveitis\u003c/p\u003e\n\u003cp\u003eRNFL\u0026nbsp; \u0026nbsp;retinal nerve fiber layer\u003c/p\u003e\n\u003cp\u003eBCVA \u0026nbsp;\u0026nbsp;best-corrected visual acuity\u003c/p\u003e\n\u003cp\u003eFA \u0026nbsp; \u0026nbsp; \u0026nbsp;fluorescein angiography\u003c/p\u003e\n\u003cp\u003eVH \u0026nbsp; \u0026nbsp; \u0026nbsp;vitreous haze\u003c/p\u003e\n\u003cp\u003eIMT \u0026nbsp; \u0026nbsp;\u0026nbsp;immunosuppression therapy\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha;\u0026nbsp; \u0026nbsp;tumor necrosis factor alpha\u003c/p\u003e\n\u003cp\u003eOCT\u0026nbsp;\u0026nbsp; \u0026nbsp;optical coherence tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIOP\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;intraocular pressure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSUN \u0026nbsp; \u0026nbsp;Standardization of Uveitis Nomenclature\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eWe greatly appreciate all participants in the study.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eYC, and CZ conceived the study; XX and YZ followed up and collected data; QL and JX analyzed the data; YC, CZ, and XX wrote the manuscript. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Key Research and Development plan of Shaanxi Province [grant number 2022SF-366].\u003c/p\u003e\n\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003eEthics statement and consent to participate\u003c/p\u003e\n\u003cp\u003eThis protocol was approved by the Ethics Committee of Xi\u0026apos;an People\u0026apos;s Hospital (Xi\u0026rsquo;an Fourth Hospital) (No.20220023), which was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eConsent to publish\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMaleki A, Anesi SD, Look-Why S, Manhapra A, Foster CS. Pediatric uveitis: A comprehensive review. SURV OPHTHALMOL. 2022;67(2):510\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. AM J OPHTHALMOL. 2000;130(4):492\u0026ndash;513.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuartier P, Baptiste A, Despert V, Allain-Launay E, Kone-Paut I, Belot A, Kodjikian L, Monnet D, Weber M, Elie C, et al. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. ANN RHEUM DIS. 2018;77(7):1003\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSonmez HK, Evereklioglu C, Gulmez SD. Prompt and Sustained Suppression of Intraocular Inflammation with Adalimumab in Pediatric Patients with Non-Infectious Uveitis Resistant to Traditional Managements: A 6-Month Follow-Up Research. OCUL IMMUNOL INFLAMM. 2023;31(10):1992\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVitale A, Casa FD, Guerriero S, Ragab G, Mauro A, Caggiano V, Cattalini M, Del GE, Favale R, Gaggiano C, et al. Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry. OPHTHALMOL THER. 2023;12(4):1957\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Julandani DA, Bagri NK, Tsang N, Clarke S, Upadhyay A, Guly C, Ramanan AV. Outcome of adalimumab monotherapy in paediatric non-infectious uveitis. PEDIATR RHEUMATOL. 2023;21(1):21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuhler EB, Adan A, Brezin AP, Fortin E, Goto H, Jaffe GJ, Kaburaki T, Kramer M, Lim LL, Muccioli C, et al. Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III. Ophthalmology. 2018;125(7):1075\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016;388(10050):1183\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, et al. Adalimumab in Patients with Active Noninfectious Uveitis. NEW ENGL J MED. 2016;375(10):932\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, Hardwick B, Hickey H, Hughes D, Woo P, et al. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. NEW ENGL J MED. 2017;376(17):1637\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAngeles-Han ST, Lo MS, Henderson LA, Lerman MA, Abramson L, Cooper AM, Parsa MF, Zemel LS, Ronis T, Beukelman T, et al. Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Juvenile Idiopathic Arthritis-Associated and Idiopathic Chronic Anterior Uveitis. ARTHRIT CARE RES. 2019;71(4):482\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKouwenberg CV, Koopman-Kalinina AV, de Boer JH. Clinical benefits and potential risks of adalimumab in non-JIA chronic paediatric uveitis. ACTA OPHTHALMOL. 2022;100(4):e994\u0026ndash;1001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeitch I, Amer R, Tomkins-Netzer O, Habot-Wilner Z, Friling R, Neumann R, Kramer M. The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric uveitis of diverse etiologies. GRAEF ARCH CLIN EXP. 2018;256(4):801\u0026ndash;08.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoe S, Heo JW, Oh BL. Quiescence and Subsequent Anterior Chamber Inflammation in Adalimumab-treated Pediatric Noninfectious Uveitis. Korean J Ophthalmol. 2020;34(4):274\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUcan GG, Yalcinbayir O, Cekic S, Yildiz M, Kilic SS. Anti-Tumor Necrosis Factor Treatment in the Management of Pediatric Noninfectious Uveitis: Infliximab Versus Adalimumab. J OCUL PHARMACOL TH. 2021;37(4):236\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. AM J OPHTHALMOL. 2005; 140(3):509\u0026thinsp;\u0026ndash;\u0026thinsp;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNussenblatt RB, Peterson JS, Foster CS, Rao NA, See RF, Letko E, Buggage RR. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005;112(5):764\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaMattina KC, Koreishi AF. What is new in paediatric uveitis? CURR OPIN OPHTHALMOL. 2018;29(5):412\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee MW, Lee TH, Won YK, Shin YI, Kim JY. Characteristics of retinal layer thickness in acute anterior uveitis: an optical coherence tomography study. ACTA OPHTHALMOL. 2020;98(1):e50\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShulman S, Goldenberg D, Habot-Wilner Z, Goldstein M, Neudorfer M. Optical coherence tomography characteristics of eyes with acute anterior uveitis. ISR MED ASSOC J. 2012;14(9):543\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKouwenberg CV, Blom LA, Vellinga SC, Bozkir I, de Boer JH, Ayuso VK. The Role of the Retinal Nerve Fiber Layer Thickness on OCT in the Evaluation of Papillitis in Childhood Uveitis. AM J OPHTHALMOL. 2023;254:62\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho H, Pillai P, Nicholson L, Sobrin L. Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring. OCUL IMMUNOL INFLAMM. 2016;24(2):194\u0026ndash;206.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong H, Zhao C, Xiao J, Gao F, Li D, Zhang M. The Efficacy and Safety of Adalimumab in Treating Pediatric Noninfectious Chronic Anterior Uveitis With Peripheral Retinal Vascular Leakage: A Pilot Study. FRONT MED-LAUSANNE. 2022;9:813696.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"TNF-α inhibitor, Adalimumab, pediatric non-infectious uveitis, anterior uveitis, treatment","lastPublishedDoi":"10.21203/rs.3.rs-4540347/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4540347/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAdalimumab (ADA) has been used for treating various types of pediatric non-infectious uveitis. Existing studies lack an examination of the correlation between the clinical characteristics of uveitis and the success rate of ADA treatment. The present study is to identify the clinical characteristic of cases that is related to the response rate of ADA treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective review of medical records was conducted for pediatric patients with non-infectious uveitis undergoing ADA treatment for a minimum of six months. The patients were stratified into two groups: apparent anterior uveitis (AAU) and with non-apparent anterior uveitis (NAAU). Outcomes including best-corrected visual acuity (BCVA), anterior chamber cell (ACC), vitreous haze (VH) grade, retinal nerve fiber layer (RNFL) thickness, fundus fluorescein angiography (FA) scores, as well as systemic immunosuppression therapy (IMT) and glucocorticoid load, were assessed. Treatment success was defined based on a composite outcome involving the aforementioned variables.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 59 patients (111 eyes), with 44 patients (83 eyes, 74.58%) falling into the AAU group and 15 patients (28 eyes, 25.42%) in the NAAU group. Following 6-month of ADA treatment in the AAU group, there was a significant improvement in BCVA (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), improved ACC (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and VH (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), decreased RNFL thickness (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), reduced FA scores (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, no significant differences were observed in BCVA, VH, RNFL thickness, FA scores between baseline and the 6-month follow-up visit in the NAAU group. There was also a significant decrease in systemic IMT and glucocorticoid dosing, comparing baseline to the 6-month follow-up visit in both the AAU (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and NAAU groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The rate of treatment success in the AAU group was significantly higher compared to that in NAAU patients (93.18% vs. 20%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eADA demonstrates superior efficacy in the treatment of pediatric non-infectious uveitis with AAU compared to NAAU.\u003c/p\u003e","manuscriptTitle":"Efficacy of Adalimumab in pediatric non-infectious uveitis with apparent and non-apparent anterior uveitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-24 17:51:09","doi":"10.21203/rs.3.rs-4540347/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-10T09:57:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-08T17:38:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-08T17:36:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2024-06-06T12:27:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2d179ae1-5873-4b89-bbff-dfbe92511590","owner":[],"postedDate":"June 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T16:04:23+00:00","versionOfRecord":{"articleIdentity":"rs-4540347","link":"https://doi.org/10.1186/s12886-025-03859-6","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-01-13 15:57:59","publishedOnDateReadable":"January 13th, 2025"},"versionCreatedAt":"2024-06-24 17:51:09","video":"","vorDoi":"10.1186/s12886-025-03859-6","vorDoiUrl":"https://doi.org/10.1186/s12886-025-03859-6","workflowStages":[]},"version":"v1","identity":"rs-4540347","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4540347","identity":"rs-4540347","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}