Vogt-Koyanagi-Harada Patients Research Articles

Clinical and Transcriptional Profiles Reveal the Treatment Effect of Adalimumab in Patients with Initial-Onset and Recurrent Vogt–Koyanagi–Harada Disease

ABSTRACT Purpose We aimed to evaluate adalimumab efficacy in patients with initial-onset or recurrent Vogt–Koyanagi–Harada (VKH) syndrome. Methods A retrospective clinical study was performed to examine the therapeutic effect of adalimumab in 22 VKH patients,16 with initial-onset and six with recurrent VKH. Another 22 patients with initial-onset VKH who did not receive adalimumab were included as controls. The main observational parameters included the central macular thickness (CMT), subfoveal choroidal thickness (SCT), best-corrected visual acuity (BCVA), anterior chamber cell grade (ACC), glucocorticoid dose (GCD), and the development of sunset glow fundus. MRNA sequencing was used to profile the tumor necrosis factor (TNF)-α pathway in peripheral blood mononuclear cells obtained from nine patients with initial-onset VKH disease, six patients with recurrent VKH, and eight healthy controls. Results In the initial-onset group, adalimumab therapy significantly improved the BCVA, CMT, SCT, and ACC. Furthermore, adalimumab significantly decreased GCD in patients with initial-onset. In patients with recurrent VKH, the SCT significantly improved after adalimumab treatment, but no significant changes in BCVA, CMT, and ACC were observed. All six patients experienced relapse during follow-up. The TNF-α pathway exhibited a significant increase in initial-onset VKH when compared with that in both healthy controls and recurrent patients. Conversely, it was suppressed in recurrent VKH when compared with that in the initial-onset or healthy control groups. Conclusions In patients with initial-onset VKH, adalimumab effectively reduces glucocorticoid dependence. However, adalimumab may not be effective for preventing relapse or providing long-term inflammation relief in patients with recurrent VKH.

Enhanced depth imaging optical coherence tomography features of two types of Vogt-Koyanagi-Harada disease: fuzzy or lost pattern of the choroidal vasculature is of diagnostic value.

This study aimed to compare enhanced depth imaging optical coherence tomography (EDI-OCT) features of exudative retinal detachment (ERD) type and optic disc (OD) swelling type Vogt-Koyanagi-Harada (VKH) disease. Hospitalized VKH patients were retrospectively reviewed and classified into the ERD type and the OD swelling type. The EDI-OCT features were then analyzed. The study included 32 ERD type and 15 OD swelling type VKH patients at the acute uveitis stage. The interval between the onset of ocular symptoms and the start of treatment in OD swelling type VKH disease was significantly longer compared to the ERD type (p < 0.001). A fuzzy or lost pattern of the choroidal vasculature was observed in 100% of VKH patients of both types. Moreover, high frequencies (greater than or equal to 50%) of fluctuations in the internal limiting membrane, interdigitation zone disruption, ERD, retinal pigment epithelium (RPE) folds, and ellipsoid zone disruption were observed in both types. Patients with OD swelling type VKH disease exhibited higher frequencies of OD swelling and hyperreflective substances above the RPE (p < 0.001 and p = 0.003, respectively), with lower frequencies of ERD and bacillary layer detachment (p = 0.012 and p < 0.001, respectively). At the convalescence stage, changes in the EDI-OCT images of 10 ERD type and 5 OD swelling type VKH patients were analyzed. The frequencies of the OCT features decreased with similar trends in both types of VKH disease. Although ERD type and OD swelling type VKH disease have their own unique characteristics, they share common EDI-OCT features. The Fuzzy or lost pattern of the choroidal vasculature that indicates choroidal inflammation may serve as a diagnostic aid for VKH disease, especially for the OD swelling type and the early-stage ERD type.

Blood Whispers: Exploring Hematologic Indicators for Diagnosing and Predicting Severity of Vogt-Koyanagi-Harada Syndrome

ABSTRACT Purpose To investigate the association of clinical findings and indocyanine green angiography (ICGA) score with inflammatory markers derived from complete blood count (CBC) parameters in patients with Vogt-Koyanagi-Harada (VKH) to determine the diagnostic and predictive role. Methods Demographic characteristics, presenting complaints, ocular findings, optical coherence tomography findings, ICGA scores and best corrected visual acuity were recorded in treatment-naive VKH patients at presentation. Patients were divided into two groups as acute stage and chronic recurrent stage. CBC parameters were noted in patients at presentation and healthy controls (HC, n = 25). Neutrophil-lymphocyte-platelet-monocyte counts, neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), monocyte/lymphocyte and systemic immune-inflammation index (SII) were recorded. The association between these markers and clinical severity were evaluated. Results Thirty-two patients with VKH (23 females/9 males) with a mean age of 34.1 ± 14.6 years were included in the study. There was an increase in neutrophil count, NLR and SII in patients with VKH compared to HC (p < 0.001). The cut-off values for these three parameters were 4.37, 2.24 and 562.35, respectively. Twenty-six patients presented in the acute stage and six patients presented in the chronic recurrent stage. Choroidal thickness, early stromal hyperfluorescence and total ICGA scores were higher in patients presenting in the acute stage (p < 0.001, 0.001 and 0.025, respectively). Patients with higher disease severity at presentation were treated earlier. Early stromal vessel hyperfluorescence and choroidal vasculitis scores were correlated with decreased lymphocyte count, increased NLR, PLR and SII (p < 0.05). Conclusion CBC-derived inflammatory parameters indicate that VKH is a systemic inflammation. These parameters can be used in the diagnosis and determination of disease severity of VKH.

A Novel Risk Stratification-Based Immunomodulatory Treatment Strategy for Vogt-Koyanagi-Harada Disease

PurposeTo develop a more tailored immunomodulatory treatment (IMT) strategy based on a novel two-arm risk stratification system in Vogt-Koyanagi-Harada (VKH) patients. DesignA retrospective clinical cohort study. Methods79 VKH patients in the acute stage were stratified into low (n = 58) and high-risk (n = 21) groups based on their exposure to risk factors. They were treated with oral glucocorticoids (GCs) plus pro re nata (PRN) or first-line IMT. Best corrected visual acuity (BCVA), sunset glow fundus (SGF) occurrence, relapse rate, and systemic adverse events were evaluated during follow-up. ResultsCompared with the low-risk group, the high-risk showed poorer BCVA at baseline (estimated difference, 0.51; 95% CI, 0.30-0.78; p < 0.001) and 6-month follow-up (estimated difference, 0.08; 95% CI, 0.00-0.08; p = 0.006), higher incidence of SGF at 12 months (52% vs 28%; RR, 1.9; 95% CI, 1.1-3.4; p = 0.040), and higher relapse rate at 6 months (24% vs 5%; RR, 4.6; 95% CI, 1.2-17.5; p = 0.028) and 12 months (52% vs 12%; RR, 4.4; 95% CI, 1.9-9.7; p < 0.001). In the low-risk cohort, no significant difference between the two IMT strategies was observed in primary outcomes. In the high-risk cohort, patients with the immediate IMT showed better BCVA (estimated difference, -0.20; 95% CI, -0.3 to -0.08; p = 0.007), lower incidence of SGF (27% vs 80%; RR, 0.3; 95% CI, 0.1-0.9; p = 0.030), and lower relapse rate (27% vs 80%; RR, 0.3; 95% CI, 0.1-0.9; p = 0.030) compared with the PRN regimen. Moreover, the immediate IMT regimen had a higher frequency of systemic adverse events than the PRN regimen (47% vs 7%; RR, 7.1; 95% CI, 2.5-20.4; p < 0.001). ConclusionsHigh-risk stratification at baseline was associated with poor prognosis. The immediate IMT regimen was only beneficial for high-risk VKH patients regarding visual outcome, SGF, and relapse rate. This study suggests a potential need for a customized IMT strategy for VKH patients.

OR11H1 Missense Variant Confers the Susceptibility to Vogt-Koyanagi-Harada Disease by Mediating Gadd45g Expression.

Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (pVal63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10-30 , odds ratio = 3.12). Functional study showes that OR11H1-A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA-sequencing find that OR11H1-A63 markedly increased growth arrest and DNA-damage-inducible gamma (GADD45G) expression. Moreover, OR11H1-A63 activates the MAPK and NF-κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF-κB pathways. Collectively, this study suggests that the OR11H1-A63 missense mutation may increase susceptibility to VKH disease in a GADD45G-dependent manner.

A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

Vogt–Koyanagi–Harada (VKH) disease is a leading cause of blindness in young and middle-aged people. However, the etiology of VKH disease remains unclear. Here, we performed the first trio-based whole-exome sequencing study, which enrolled 25 VKH patients and 50 controls, followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations. A total of 15 de novo mutations in VKH patients were identified, with one of the most important being the membrane palmitoylated protein 2 (MPP2) p.K315N (MPP2-N315) mutation. The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions. Additionally, this mutation appears rare, being absent from the 1000 Genome Project and Genome Aggregation Database, and it is highly conserved in 10 species, including humans and mice. Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis (EAU). In vitro, we used clustered regularly interspaced short palindromic repeats (CRISPR‒Cas9) gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315. Levels of cytokines, such as IL-1β, IL-17E, and vascular endothelial growth factor A, were increased, and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells. Mechanistically, the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315, as shown by LC‒MS/MS and Co-IP, and resulted in activation of the ERK3/IL-17E pathway. Overall, our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.

Association of ZC3HAV1 single nucleotide polymorphisms with the susceptibility of Vogt-Koyanagi-Harada Disease

BackgroundPolymorphisms of genes related to the immune response have been reported to confer susceptibility to Vogt-Koyanagi-Harada (VKH) disease. This study was carried out to determine whether zinc finger CCCH-type containing antiviral 1 (ZC3HAV1) and tripartite motif-containing protein 25 (TRIM25) genetic polymorphisms are associated with this disease.MethodsA total of 766 VKH patients and 909 healthy individuals were enrolled in this two-stage case-control study. Thirty-one tag single nucleotide polymorphisms (SNPs) of ZC3HAV1 and TRIM25 were genotyped by MassARRAY System and iPLEX Gold Genotyping Assay. Allele and genotype frequencies were analyzed by the χ2 test or Fisher’s exact test. Cochran-Mantel-Haenszel test was used to assess the pooled odds ratio (OR) in the combined study. A stratified analysis was performed in terms of the major clinical features of VKH disease.ResultsWe found a statistically significant increased frequency of the minor A allele of ZC3HAV1 rs7779972 (P = 1.50 × 10− 4, pooled OR = 1.332, 95%CI = 1.149–1.545) in VKH disease as compared with controls by using the Cochran-Mantel-Haenszel test. The GG genotype of rs7779972 showed a protective association with VKH disease (P = 1.88 × 10− 3, OR = 0.733, 95%CI = 0.602–0.892). There was no difference regarding the frequency of the remaining SNPs between VKH cases and controls (all P > 2.08 × 10− 3). The stratified analysis showed no significant association of rs7779972 with the major clinical characteristics of VKH disease.ConclusionOur study indicated that the ZC3HAV1 variant rs7779972 might confer susceptibility to VKH disease in Han Chinese.

Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China

BackgroundsTo characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China.MethodsIn total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed.ResultsAmong the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences.ConclusionPosterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.

Classification of Vogt-Koyanagi-Harada disease using feature selection and classification based on wide-field swept-source optical coherence tomography angiography.

Background: Vogt-Koyanagi-Harada (VKH) disease is a common and easily blinded uveitis entity, with choroid being the main involved site. Classification of VKH disease and its different stages is crucial because they differ in clinical manifestations and therapeutic interventions. Wide-field swept-source optical coherence tomography angiography (WSS-OCTA) provides the advantages of non-invasiveness, large-field-of-view, high resolution, and ease of measuring and calculating choroid, offering the potential feasibility of simplified VKH classification assessment based on WSS-OCTA. Methods: 15 healthy controls (HC), 13 acute-phase and 17 convalescent-phase VKH patients were included, undertaken WSS-OCTA examination with a scanning field of 15 × 9mm2. 20 WSS-OCTA parameters were then extracted from WSS-OCTA images. To classify HC and VKH patients in acute and convalescent phases, two 2-class VKH datasets (HC and VKH) and two 3-class VKH datasets (HC, acute-phase VKH, and convalescent-phase VKH) were established by the WSS-OCTA parameters alone or in combination with best-corrected visual acuity (logMAR BCVA) and intraocular pressure (IOP), respectively. A new feature selection and classification method that combines an equilibrium optimizer and a support vector machine (called SVM-EO) was adopted to select classification-sensitive parameters among the massive datasets and to achieve outstanding classification performance. The interpretability of the VKH classification models was demonstrated based on SHapley Additive exPlanations (SHAP). Results: Based on pure WSS-OCTA parameters, we achieved classification accuracies of 91.61% ± 12.17% and 86.69% ± 8.30% for 2- and 3-class VKH classification tasks. By combining the WSS-OCTA parameters and logMAR BCVA, we achieved better classification performance of 98.82% ± 2.63% and 96.16% ± 5.88%, respectively. Through SHAP analysis, we found that logMAR BCVA and vascular perfusion density (VPD) calculated from the whole field of view region in the choriocapillaris (whole FOV CC-VPD) were the most important features for VKH classification in our models. Conclusion: We achieved excellent VKH classification performance based on a non-invasive WSS-OCTA examination, which provides the possibility for future clinical VKH classification with high sensitivity and specificity.

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

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

Clinical Profile of Patients with Vogt–Koyanagi-Harada Disease at a Tertiary Eye Hospital in Bangladesh

Background: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disease characterized by bilateral panuveities affecting the young adults. Approximately 3% of the uveitis patients are VKH patients. Objective: To assess the clinical profile of patients with Vogt-Koyanagi- Harada (VKH) disease.

Prospective Study of Clinical Characteristics and Visual Outcome in Vogt–Koyanagi–Harada Syndrome in a Tertiary Eye Hospital in South India

Purpose: To describe the demographic pattern, clinical characteristics, treatment modalities, and visual outcome in Vogt–Koyanagi–Harada (VKH) disease patients observed at a tertiary eye care centre in South India. Methods: A prospective chart analysis of 38 patients with VKH disease. Results: Of the 38 VKH patients, 31 (81.6%) were female, the mean age was 39.8 years, and the median duration of symptoms was 10 days (range: 2 to 180 days). The most common ocular complaint was a defective vision (70 eyes or 92.1%). Extraocular manifestations were headache (13 patients or 34.2%) and tinnitus (4 patients or 10.5%). Twenty-four patients (63.2%) presented with bilateral panuveitis, and 12 patients (31.6%) had posterior uveitis. The most common posterior segment presentation included bilateral serous retinal detachment (100%), disc oedema (37 eyes or 48.7%), and vitritis (31 eyes or 40.8%). All patients (100%) were treated with oral and topical prednisolone, based on the ocular inflammation status, 9 patients (23.7%) required dexamethasone (intramuscular), 39 eyes (51.3%) required posterior subtenon triamcinolone, 16 patients (28.9%) required methotrexate, 1 (2.6%) required cyclophosphamide, 1 (2.6%) required azathioprine. At the final visit, the majority of the patients had statistically significant good visual outcomes. Conclusion: Prompt diagnosis and early initiation of treatment with systemic, local steroid and immunosuppressive therapy showed faster recovery with good visual outcome.

Bacillary Layer Detachment in Acute Vogt-Koyanagi-Harada Disease.

To evaluate the frequency and treatment response of eyes with bacillary layer detachment (BLD) in acute Vogt-Koyanagi-Harada (VKH) disease using spectral-domain optical coherence tomography (SD-OCT). We retrospectively reviewed the medical records of 58 eyes of acute VKH patients with at least 6 months of follow-up between January 2009 and March 2021. SD-OCT, color fundus photographs, and fluorescein angiography images were analyzed in all patients. The study included 58 eyes of 29 patients. BLD was detected in 33 of the 58 eyes (56.9%) at baseline. Mean serous retinal detachment (SRD) height was 918.50±336.64 μm in the BLD group and 215.33±167.83 μm in the group without BLD (p<0.05). A positive correlation was found between SRD height and the presence of BLD (r=0.783, p<0.05). BLD was significantly more common in patients with a baseline SRD height greater than 500 μm (p<0.05). As subfoveal central choroidal thickness (CCT) could not be measured by enhanced depth imaging-OCT at baseline due to extreme choroidal thickness in all eyes, the earliest post-treatment CCT measurements were analyzed. At the completion of pulse steroid therapy, mean CCT was 425±82.87 μm in the BLD group and 385.58±82.87 μm in the group without BLD (p=0.04). The mean time to BLD resolution was 12.88±6.5 days (range: 2-26). BLD is a common tomographic finding in eyes with acute VKH disease and can be differentiated from the associated SRD through careful SD-OCT analysis. Though it is mostly observed in patients with more serious disease, the presence of BLD has no negative effect on long-term visual function.

Clinical relevance of fibrin membranous structures in the intra-photoreceptor outer segment separation on spectral domain optical coherence tomography (SD-OCT) in initial-onset acute Vogt-Koyanagi-Harada disease.

The purpose of the study was to investigate clinical relevance of fibrin membranous structure (FMS) in the photoreceptor outer segments on spectral-domain optical coherence tomography (SD-OCT) in untreated initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. Clinical charts of 39 patients (78 eyes) diagnosed with initial-onset VKH disease were retrospectively reviewed. Age, gender, period from the onset of symptoms to first visit, visual acuity (VA), intraocular pressure (IOP), anterior chamber cells, serous retinal detachment (SRD), SD-OCT findings, as well as fluorescein (FA), and indocyanine green angiography (ICGA) were collected. FMS was observed in 24 out of 39 VKH patients in either eye (61.5%). VKH patients with FMS (FMS group) were significantly younger and had the shorter period from the onset of symptoms to the first visit compared with those without FMS (non-FMS group). Mean logMAR VA and proportion of pooling of dye, mean central retinal thickness (CRT) were significantly higher in FMS group than in non-FMS group. In contrast, hyperfluorescence of the optic disc on FA was more in non-FMS group than in FMS group. Significant positive correlations between CRT and logMAR VA or IOP were only observed in the FMS group. Total amount of corticosteroids was significantly greater in FMS group than in non-FMS group. However, there were no significant differences in LogMAR VA and IOP between two groups at 6months after treatment initiation. FMS on SD-OCT is a critical feature observed in the early stage of initial-onset acute VKH disease, which is more common in younger patients and is related to the disease activity.

Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt-Koyanagi-Harada Disease.

Vogt-Koyanagi-Harada (VKH) disease is a common type of uveitis that leads to blindness. The clinical manifestations and treatment solutions are different between initial-onset and recurrent VKH. Therefore, identifying the microRNA (miRNA) profiles from initial-onset and recurrent VKH patients may shed light on the molecular mechanisms underlying the pathogenesis of VKH disease. RNAs isolated from peripheral blood mononuclear cells (PBMCs) from patients with initial-onset VKH, recurrent VKH, and healthy individuals were subjected to high-throughput miRNA sequencing. Pairwise analysis of miRNA sequencing data between groups was conducted to identify differentially expressed miRNAs (DEMs), which were verified using real-time quantitative polymerase chain reaction. After receiver operating characteristic analyses, we found that hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers of different VKH stages. DEMs were classified into three groups based on their differential expression: DEMs in initial-onset stage, DEMs in recurrent stage, and DEMs common between both VKH stages (shared DEMs). Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes identified the mitogen-activated protein kinase, tumor necrosis factor, and mechanistic target of rapamycin kinase pathways as significantly enriched among the target genes of recurrent stage and shared DEMs. Furthermore, we mapped a network of competing endogenous RNAs for hsa-miR-206, which we used to identify putative targets for VKH treatment. Hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers for different stages of VKH. Additionally, our competing endogenous RNA network of hsa-miR-206 provides a new direction for VKH treatment.

Efficacy and Safety of Adalimumab for Exacerbation or Relapse of Ocular Inflammation in Patients with Vogt-Koyanagi-Harada Disease: A Multicenter Study

ABSTRACT Purpose We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. Methods Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. Results The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. Conclusions ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.

Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients.

BackgroundHigh dose systemic glucocorticoid is the main therapy of treatment-naïve Vogt-Koyanagi-Harada (VKH) disease. However, series side effects induced by high dose systemic glucocorticoid frequently occur, which makes alternative therapy necessary for certain patients. This study sought to compare the efficacy and safety of systemic glucocorticoid-free (SGF) therapy with conventional therapy (CT) as an initial treatment for VKH patients.MethodsVKH patients who had not been systemically treated were enrolled. Patients were allocated into 2 therapeutic groups depending on their treatments. In CT group, patients received systemic glucocorticoid plus immunosuppressants (IS), and in SGF group, patients received adalimumab (ADA) plus IS. Patients received approximately 12 months treatment and visit monthly. The outcome parameters included the changes of best-corrected visual acuity (BCVA), intraocular inflammation (including anterior chamber cell grade and vitritis grade) and central macular thickness (CMT) (the change values define as the final-visit values subtracted from baseline counterparts). Other outcomes included the relapses times of ocular inflammation, adverse events (AEs), changes of optic nerve inflammation (ONI) and intraocular/extraocular manifestations.ResultsA total of 30 patients (60 eyes) were included. with 19 patients (38 eyes) in CT group and 11 patients (22 eyes) in SGF group. After approximately 1 year of treatment, the improvements of BCVA were slight better in the SGF group (0.57±0.23) than in the CT group (0.40±0.26), (P=0.014). In both groups, the ocular inflammatory improvements in both groups were similar, with an improvement of AC cell grade of −1.5 (−2, −0.5) in CT group versus −1 (−2, −1) in SGF group (P=0.367); improvement of vitritis grade was 0 (−1.25, 0) in CT group and −1 (−1, −1) in SGF group (P=0.050). The improvement in CMT was similar in both groups, with −523.47±412.09 µm in CT group and −362.73±375.73 µm in SGF group (P=0.572). The mean number of relapses was 1 (0, 2) in the CT group and 0 (0, 2) in the SGF group (P=0.372). No severe AEs were observed in this study.ConclusionsSGF therapy is effective, safe, and well-tolerated in treatment-naïve VKH patients. SGF therapy seems to be a feasible option in patients with existing systemic diseases intolerant to glucocorticoid.

Adalimumab in Vogt-Koyanagi-Harada Disease Refractory to Conventional Therapy.

Background: No study explores the effectiveness of adalimumab in sight-threatening Vogt-Koyanagi-Harada (VKH) patients in China.Objective: To evaluate the short-term effectiveness and safety of adalimumab (ADA) in patients with sight-threatening Vogt-Koyanagi-Harada (VKH) disease refractory to conventional therapy.Methods: Medical records of VKH patients who had been treated with systemic glucocorticoids and immunosuppressants but whose condition was poorly controlled were collected and analyzed. Primary outcomes comprised of best-corrected visual acuity (BCVA), intraocular inflammation, relapses, and glucocorticoid-sparing effects. Other outcomes included central macular thickness (CMT), intraocular manifestations and adverse events (AEs).Results: Nine refractory VKH patients with a median age of 30 (16, 43) years old were enrolled in this study and received treatment for a median of 10 (7, 11) months. Mean BCVA improved from LogMar 0.63 ± 0.50 (20/72 or 0.36 ± 0.26 in Snellen chart) at baseline to LogMar 0.50 ± 0.37 (20/82 or 0.41 ± 0.28 in Snellen chart) at final visit (P = 0.090). The anterior chamber cell grade decreased from 2 (1.75, 3)+ at baseline to 0.5 (0, 1.25)+ cell at final visit (P < 0.001). The vitritis grade decreased from 1 (1, 1) + cell at baseline to 0 (0, 1)+ cell at final visit (P < 0.001). Patients suffered a median of 1 (0, 2) relapse during treatment. CMT remained stable from 238.50 ± 144.94 μm at baseline to 219.28 ± 77.20 μm at final visit (P = 0.553). The mean prednisone dosage decreased from 21.91 ± 18.39 mg/d to 2.73 ± 4.10 mg/d (P = 0.005). No severe AEs were found during treatment.Conclusions: The outcomes indicated that ADA was an effective and safe option for VKH patients refractory to conventional therapy by controlling inflammation, preserving visual function and reducing the daily glucocorticoid dose.

Adalimumab treatment for chronic recurrent Vogt-Koyanagi-Harada disease with sunset glow fundus: A multicenter study

We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.

Analyses of circRNA and mRNA Profiles in Vogt-Koyanagi-Harada Disease.

Recent studies revealed that circular RNAs (circRNAs) are important in numerous biological process and involved in autoimmune diseases. However, their role in Vogt–Koyanagi–Harada (VKH) disease, a classical autoimmune disease, is not yet known. This research aimed to study the expression profile of mRNAs, microRNAs (miRNAs) and circRNAs and investigate the influence of circRNAs on the pathogenesis of VKH disease. We identified circRNAs, miRNAs, and mRNAs expression profiles in CD4+ T cells between 4 VKH patients and 3 healthy controls using the whole-transcriptome sequencing (RNA-seq) technique. We discovered that a total of 5088 mRNAs, 451 circRNAs and 433 miRNAs were differently expressed. The GO and KEGG pathway enrichment analyses were performed for significantly differentially expressed circRNAs and mRNAs. GSEA was conducted for all mRNAs. The functional enrichment suggested that the inflammatory response, the adaptive immune response, NF-kappa B signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation and T cell receptor signaling pathway were associated with VKH disease. In addition, based on the immune-related genes we screened, the circRNA-miRNA-mRNA ceRNA network was analyzed and constructed. Ten differently expressed mRNAs (LAT, ZAP70, ITK, ICOS, RASGRP1, PAG1, PLCG1, PRKCQ, LCK, CARD11) and 5 differently expressed circRNAs (hsa_circ_0033144, hsa_circ_0000233, hsa_circ_0000396, hsa_circ_0001924, hsa_circ_0001320) were selected to be validated by Real-time qPCR (RT-qPCR). The results of RT-qPCR turned out to be consistent with RNA-seq data. Further analysis showed that hsa_circ_0001320 and hsa_circ_0001924 may serve as crucial candidate marker genes of VKH disease. These results reveal that circRNAs may have a crucial immunomodulatory function in the pathophysiological process of VKH disease.