Vogt-Koyanagi-Harada Patients Research Articles

Vogt-Koyanagi-Harada Disease Presenting as Papillitis vs. Classic Serous Retinal Detachment: A Comparative Analysis of Outcomes

ABSTRACT Background To compare the treatment outcome and visual prognosis of Vogt-Koyanagi-Harada (VKH) disease presenting as papillitis vs. serous retinal detachment (SRD). Methods Retrospective comparative cohort study of 35 patients with previously unknown VKH diagnosis, followed-up for ≥6 months. Outcomes measured: (1) time to achieve inflammatory control; (2) VKH relapse; (3) ocular complications (glaucoma, sunset glow fundus, cataract, and vision loss ≥2 Snellen lines); and (4) chances for developing a chronic-recurrent disease. Results Females predominated in both groups: 12/16 (75%) papillitis and 18/19 (94.7%) SRD. The mean age at presentation was 29 ± 12 years in the papillitis and 36 ± 14 years in the SRD group (p = 0.119), with an overall median follow-up of 26 months (6–180 months). The papillitis-onset VKH group’s mean time elapsed between symptoms onset and initial treatment was shorter (2.9 ± 1.0 vs. 4.6 ± 2.8 weeks, p = 0.024). Anterior segment inflammation was lower (56% vs. 79%, p = 0.018), requiring a shorter corticosteroids treatment duration (12.8 ± 16.1 vs. 32.7 ± 34.1 months, p = 0.040), achieving an earlier inflammatory control (1.9 ± 0.6 vs. 4.1 ± 3.2 months, p <0.001) with fewer ocular complications (13% vs. 74%, p <0.001), including sunset glow fundus (SGF) (0% vs. 63%, p <0.001). Conversely, SRD-onset VKH was a risk factor for developing disease relapse (HR: 4.53; 95% CI: 1.31–15.69, p = 0.017), ocular complications (OR: 19.60, 95% CI: 3.24–118.50, p = 0.001), and chronic-recurrent disease (OR: 20.63; 95% CI: 2.24–189.84, p = 0.008). Conclusion Mexican-mestizo VKH patients with papillitis-onset VKH disease showed earlier inflammatory control, fewer recurrences, and better visual and ocular complication outcomes.

Reduced contrast sensitivity function and outer retina thickness in convalescent Vogt-Koyanagi-Harada disease

Abstract Background To evaluate contrast sensitivity function (CSF) in convalescent Vogt-Koyanagi-Harada (VKH) disease and investigate the relationship between CSF and chorioretinal thickness in VKH patients with and without sunset glow fundus (SGF). Methods This is a cross-sectional study. Seventy-six eyes of VKH patients and 56 eyes of normal controls were evaluated. Patients were divided into SGF and non-SGF groups. The best-corrected visual acuity (BCVA) of all the participants was ≤0.0 logMAR. Their CSF and macular chorioretinal thickness were measured with quantitative CSF (qCSF) and Optical Coherence Tomography (OCT) and compared using repeated measures analysis of variance at the group level. Relationships between CSF and macular chorioretinal thickness were evaluated using generalized estimating equations. Results The CSF was significantly impaired in the SGF group compared to that in the control group (p = 0.001), especially at medium and high spatial frequencies. No significant CSF difference was found between the non-SGF group and control group, nor between the SGF and non-SGF groups. Compared to the controls, outer retinal thickness (ORT) in both VKH subgroups was significantly reduced (P &lt; 0.001 or 0.005, respectively), although their outer nuclear layer thickness (ONLT) and choroidal thickness (CT) were not significantly different (both P = 1.000, P = 0.829 or 0.112, respectively). We found no significant correlation between CSF metrics and outer retinal thickness. Conclusions Despite good recovery of visual acuity, reduced CSF and outer retina thickness were found in convalescent VKH patients. CSF may be an important and sensitive metric to evaluate functional vision in VKH disease.

Effects of pregnancy on the clinical course and treatment outcomes of Vogt-Koyanagi-Harada disease.

To describe the clinical course and treatment outcomes of Vogt-Koyanagi-Harada (VKH) disease during pregnancy. This retrospective study compares the clinical course and outcomes in pregnant and nonpregnant women with VKH. All VKH patients who were pregnant at presentation or on follow up and age-matched nonpregnant female controls during the study period (2013-2022) were included. Their best-corrected visual acuity (BCVA), clinical presentations, and treatment outcomes were analyzed. Among the 532 female VKH patients, nine (1.7%) were included. Thirty nonpregnant patients were included as control. At presentation, the mean age in the study group was 26 years ± 6.48 standard deviation (SD) compared to the control group (mean 25.1 years ± 3.04). The mean BCVA was comparable between the two groups at presentation (study group 1.35 logarithm of the minimum angle of resolution [logMAR] vs. control group 0.76 logMAR; P = 0.05) and the final follow-up (study group 0.65 logMAR vs. control group 0.35 logMAR; P = 0.15). Participants with anterior segment inflammation (study group 77.7% vs. control group 70%; P = 0.65), the disease stage (early-stage VKH: study group 88.8% vs. control group 73.3%; P = 0.33), and disease exacerbation (study group 33.3% vs. control group 26.6%; P = 0.69) were all comparable between the study and control groups. Following treatment, 66.6% and 46.6% of the study and control groups, respectively, had sunset glow fundus (P = 0.29). At the last follow-up, 44.4% and 26.6% of the study and control groups, respectively, had subretinal fibrosis (P = 0.31). Though pregnancy is an immunomodulatory state, the clinical course of VKH in pregnant patients can be similar to that of nonpregnant women and needs close monitoring and follow-up.

Vascular Changes and Irreversible Complications in 120° Fundus Using Widefield SS-OCTA in Vogt-Koyanagi-Harada Disease.

To characterize the changes of fundus corresponding to 120° field of view in chronic Vogt-Koyanagi-Harada (VKH) disease in the quiescent phase, and explore the associations with irreversible complications in the fundus utilizing widefield swept source optical coherence tomography angiography (SS-OCTA). Prospective cross-sectional study. Sixty-nine chronic VKH patients (115 eyes) and 55 healthy controls (110 eyes) were included and underwent widefield SS-OCTA. Univariate analyses of variations in retinal and choroidal vessel density (VD), choroidal volume, and choroidal vascularity index (CVI) in VKH patients with different disease durations and the controls were conducted. Logistic regression analysis was employed to identify the associations with irreversible complications including choroidal neovascularization, vasoproliferative tumour of the retina, and chorioretinal atrophy. The Welch's analysis of variance showed lower VD of superficial retina, deep retina, choriocapillaris, and large-sized and medium-sized vessels of the choroid (LMVC), and choroidal volume and CVI in the patients with disease duration > 24 months compared to those with disease duration ≤ 24 months (all P≤0.011). The regression analysis revealed the disease duration (P=0.008; OR=1.02, 95%CI=1.005-1.035) and VD of LMVC (P=0.001; OR=0.707, 95%CI=0.575-0.87) were significantly correlated with the irreversible complications. Chronic VKH patients in the quiescent phase with disease duration > 24 months exhibit more severe decreased VD in each layer of the retina and choroid, reduced choroidal volume and sparse choroidal vascularity compared to those with disease duration ≤ 24 months. Prolonged duration and decreased VD of LMVC were associated with irreversible complications in the fundus.

Author Reply to Letter to the Editor: In Response to: Comment on Fonollosa et al.‘s “Hyper-Reflective Outer Nuclear Layer (HONL) in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia”

ABSTRACT We have recently described an OCT sign in two patients (one with Vogt-Koyanagi-Harada (VKH) and the other with Sympathetic Ophthalmia) consisting of hyperreflectivity of the outer nuclear layer (HONL) that subsequently evolved into outer retina atrophy and associated with poor functional outcomes. Ali et al. have published a comment on our letter regarding HONL. They have evaluated it in 90 eyes of VKH patients. It was observed in 37 eyes (41.1%) and no associations were found between HONL and structural outcomes or final visual acuity, and no cases of retinal atrophy were described. In the present author's reply, we point out two reasons for these contradictory observations. First, we considered HONL a full thickness hyperreflectivity of the outer nuclear layer, whereas they included cases with partial thickness hyperreflectivity, hence probably milder cases. Second: they have assessed visual function by means of visual acuity, so cases with extrafoveal involvement whose functional deficiency might only be measured by other tests (i.e. visual field) might have been missed.

Dynamic Changes of Fundus and Predictors of Visual Prognosis in New-Onset Vogt-Koyanagi-Harada Disease

ABSTRACT Purpose To characterize the dynamic changes of fundus in Vogt-Koyanagi-Harada (VKH) disease through enhanced spectral-domain optical coherence tomography (EDI-OCT) and explore the predictors of visual prognosis. Methods In this retrospective cohort study, a total of 2152 VKH patients referred to our uveitis center from January 2013 to April 2022 were screened; 151 new-onset VKH patients (299 eyes) and 82 healthy controls (164 eyes) were included. The manifestations of fundus at baseline, 1 month, 3 months, and 12 months after treatment were analysed and their relevance to visual prognosis were evaluated. Results After retinal detachment (RD) (97.3%) and optic disc swelling (100%) presented at baseline, retinal reattachment (81.6%) and the granular hyperreflective depositions at the retinal pigment epithelium (RPE) (61.5%) were observed at month 1. The RPE and ellipsoid zone rearrangement accompanying interdigitation zone attenuation (57.9%) was noted finally. Choroidal thickness of patients was higher than that in the controls at baseline and month 1 (both P < 0.001). Best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]) (P < 0.001; OR, 4.01), subretinal fibrinoid exudate (P < 0.001; OR, 3.9) and RPE folds (p = 0.001; OR, 2.39) at baseline, and the RD at month 1 (P < 0.001; OR, 3.42) were associated with visual prognosis. Conclusions New-onset VKH patients after treatment exhibited dynamic changes in the fundus especially the outer retina during a 12-month period. The BCVA, subretinal fibrinoid exudate, and RPE folds at baseline, and RD at month May 1, serve as predictors of visual prognosis.

Outcomes in Patients With Vogt–Koyanagi–Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial

PurposeTo compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. MethodsA subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). ResultsNinety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. ConclusionsMTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. Trial RegistrationClinicalTrials.gov Identifier: NCT 0182929

Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease

BackgroundThis study explores prognostic factors influencing Vogt-Koyanagi-Harada (VKH) disease and observes the efficacy and safety of Adalimumab (ADA) in treating recurrence in Vogt-Koyanagi-Harada (VKH) patients.MethodsA retrospective study was conducted on all patients diagnosed with VKH disease at Beijing Tongren Hospital between 2020 and 2023. Clinical data included initial and final visual acuity, age, gender, ocular complications, treatment modalities, disease duration, and recurrence frequency.ResultsA total of 62 VKH patients were included, comprising 34 in the acute-resolved group and 28 in the chronic-recurrent group. The mean age of patients in the acute-resolved group was 38.29 ± 15.46 years, while the mean age of chronic-recurrent group had a 49.00 ± 16.43 years. Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002). During follow-up, ocular complications were observed in 29.4% of the acute-resolved group patients and 41.7% of the chronic-recurrent group patients (P = 0.006). “Sunset glow fundus” was observed in 23.5% of the acute-resolved group and 64.3% of the chronic-recurrent group patients (P = 0.001). Poor initial BCVA (P = 0.046) and the occurrence of “sunset glow fundus” (P = 0.040) were significantly associated with progression to the chronic recurrent phase. Logistic regression analysis revealed that older age at onset (P = 0.042) and the occurrence of “sunset glow fundus” (P = 0.037) were significant predictors for progression to the chronic recurrent phase. ADA significantly reduced anterior chamber inflammatory cells (P = 0.000) and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent group, and markedly decreased the recurrence rate in VKH patients (P = 0.009).ConclusionIn comparison to acute-resolved patients, chronic-recurrent patients exhibited poorer initial BCVA and a significantly increased incidence of “sunset glow fundus.” Older age at onset and the occurrence of “sunset glow fundus” at diagnosis are crucial predictive factors for VKH patients progressing to the chronic recurrent phase. ADA effectively alleviates refractory VKH disease and is generally well-tolerated.

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.