Vogt-Koyanagi-Harada Research Articles

Outcomes of retinal pigment epithelial detachment in Vogt-Koyanagi-Harada disease: a longitudinal analysis

BackgroundThe aim of this study was to report the clinical profile and outcomes of retinal pigment epithelial detachment (PED) in Vogt-Koyanagi-Harada (VKH) disease, and to evaluate the correlation between PED and the subsequent development of central serous chorioretinopathy (CSC) throughout the whole corticosteroid treatment course.MethodsThe retrospective study enrolled a total of 470 eyes with VKH, and 12 eyes with VKH and PED were recruited. Patients were divided into two groups according to the CSC onset or not throughout the whole course (the CSC group and non-CSC group). Best-corrected visual acuity (BCVA) improvement, and PED angle (PEDA, the angle between the two lines of the vertex of the lifted retinal pigment epithelium to the two edge points of the Bruch membrane) were compared between the two groups.ResultsCSC developed at the site of the PED in 5 of the 12 eyes with PED, while in the remaining 7 eyes PED gradually resolved following therapy. The prevalence of PED and CSC in VKH was 2.55% (12/470) and 1.06% (5/470), respectively. BCVA improvement in the non-CSC group was greater than that in the CSC group, but without a statistical difference (P = 0.25). PEDA was significantly smaller in the CSC group than in the non-CSC group (P = 0.03).ConclusionPEDA is an ideal parameter to reflect hydrostatic pressure and stretches for RPE. As PED predisposes to the development of CSC in selected VKH eyes, PEDA may be a valuable predictive factor for the development of classic CSC in VKH cases.

Vogt-Koyanagi-Harada Disease Presenting as a Schizophrenia Spectrum Disorder: A Case Report

Introduction: Numerous autoimmune disorders accompany with psychosis. The Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease with no reports about its concomitance with psychosis so far. Case Presentation: We report the co-occurrence of schizophrenic spectrum diseases with VKH for the first time. They have common manifestations such as aggression, agitation, and self-talking, subsiding after chemotherapy. Workup evaluation was performed by computed tomography (CT) scan, magnetic resonance imaging (MRI), electroencephalography (EEG), lumbar puncture (LP) study, IQ test, lab tests for hepatitis and other infections, and retinal angiography and sonography. The patient underwent corticosteroid therapy, immunosuppressive therapy, risperidone, propranolol, and trihexyphenidyl. Conclusions: Our results showed the significant role of autoimmunity in the genesis of psychosis. On the other hand, unusual manifestations and slow response to treatment in these patients show that autoimmune disorders with psychosis may worsen the prognosis of psychosis.

Posterior ocular manifestations following BNT162b2 mRNA COVID-19 vaccine: a case series.

To report the occurrence of posterior ocular adverse events following the administration of the BNT162b2 mRNA vaccine against SARS-CoV-2. A retrospective consecutive case series, in which the medical files of patients presenting with ocular adverse events within 30days of the vaccine inoculation, were analyzed. Four patients (2 females) were included in the study. The diagnoses included: posterior scleritis, paracentral acute middle maculopathy, herpes panuveitis, and Vogt-Koyanagi-Harada (VKH)-like uveitis. Three of the patients had no relevant ocular history, but the patient who developed scleritis was in remission without medical therapy for four years, until the flare-up, which occurred one day after the vaccine. All patients improved with treatment. Though a causal relationship cannot be definitively established, the temporal relationship suggests a possible link between the COVID-19 vaccine and the posterior ocular complications. The benefits of vaccination clearly outweigh the potential adverse effects; however, ophthalmologists should be aware of the potential for vaccine-associated uveitis.

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.

Adalimumab in Vogt–Koyanagi–Harada disease

A 30-year-old Chinese woman presented to the ophthalmology department with bilateral blurry vision.; she was diagnosed with incomplete Vogt–Koyanagi–Harada (VKH). The treatment consisted of prednisolone infusion followed by a change of oral hormones. However, adalimumab subcutaneous injection was used instead because of the ineffectiveness of hormone therapy and the patient's reluctance to take oral hormones. After effective monotherapy with adalimumab, the inflammation was stable and inactive without recurrence at follow-up.

Etiology of Pediatric Uveitis in a Tertiary Pediatric Eye Hospital in Egypt

ABSTRACT Purpose To report the causes of childhood-onset uveitis in a tertiary pediatric ophthalmology hospital in Egypt. Methods Retrospective study of the medical records of all uveitis patients following up at a tertiary pediatric ophthalmology hospital in Egypt from January 2017 to December 2020. Results The present study included 388 patients. The most common anatomical category was intermediate uveitis (30.4%), and around half of these children had pars planitis. This was followed by panuveitis (25.5%), posterior uveitis (23.5%), and anterior uveitis (20.6%), in decreasing frequency. Juvenile idiopathic arthritis, toxoplasmosis, and Vogt–Koyanagi–Harada syndrome were the most common causes of anterior uveitis, posterior uveitis, and panuveitis respectively. Cataract (40.5%), glaucoma (33.8%), and cystoid macular edema (31.6%) were the most frequent ocular complications. Conclusion The present report provides the relative prevalence of the different anatomical types of uveitis, as well as their main causes in a cohort of Egyptian patients with childhood-onset uveitis.

Demography and clinical pattern of newly diagnosed uveitis patients in Malaysia

IntroductionUveitis is one of the common causes of visual impairment in Malaysia. It remains a challenging entity to diagnose and manage due to variation in its clinical presentation. This study aims to observe the demographic and clinical pattern of cases from the participating ophthalmology units in Malaysia.MethodsThis study involved prospective and multicentered data collection for patients newly diagnosed with uveitis from 1st January 2018 to 31st December 2018. Variables collected and analyzed included age, gender, ethnicity, nationality, state of origin, laterality, granulomatous or non-granulomatous uveitis, and etiology of uveitis.ResultsA total of 1199 newly diagnosed uveitis patients were analyzed within the study period. There was a significant association between the anatomical location of uveitis with age at presentation. The percentage of patients with anterior uveitis was higher in the ‘40 to 60’ years and ‘above 60’ years age groups at 52.1% (n = 210) and 61.3% (n = 114) respectively. In contrast the percentage of patients with posterior and panuveitis was higher in the 1 to 20 and 20 to 40 years age groups at 51.4% (n = 54) and 48.7% (n = 246) respectively.Sixty three percent of the patients presented with unilateral uveitis (n = 760, p < 0.001) vs bilateral. Non-granulomatous uveitis comprised 84.5% of all patients (n = 1013, p < 0.001) compared to granulomatous uveitis. Non-infectious etiology contributed to 65.7% of all patients (n = 788, p < 0.001) with the majority being unclassifiable uveitis (n = 686, 57.2%,). Specific inflammatory entities contributed to only 8.5% (n = 102) of the non-infectious causes with Vogt-Koyanagi-Harada (VKH) syndrome being the most common (n = 25, 2.1%,). Infectious uveitis comprised 34.3% (n = 411) with tubercular (TB) uveitis (n = 105, 8.8%) and viral uveitis (n = 107, 8.9%) contributing the most followed by ocular Toxoplasmosis (n = 93,7.8%).]ConclusionThis study has highlighted the demographic data and common causes of uveitis in Malaysia.

Correlation Between Hyperreflective Foci in the Choroid and Choroidal Discoloration in Vogt-Koyanagi-Harada Disease.

PurposeTo investigate the distribution of hyperreflective choroidal foci (HCF) in eyes with Vogt-Koyanagi-Harada (VKH) disease.MethodsWe included 22 eyes of 11 patients with VKH disease in the convalescent stages and 22 eyes of age- and sex-matched normal controls. HCF were quantified using en face optical coherence tomography (OCT) images of the choroid, and the degree of fundus pigmentation was determined by the color balance of the fundus photographs. The results were then analyzed between the eyes with and without sunset glow fundus (SGF).ResultsThe median age of patients with VKH disease was 58.0 (range 54.0–65.0) years, and median disease duration was 66.4 (range 8.5–147.7) months. In 22 eyes with VKH, the number and total area of HCF were correlated with the degree of fundus pigmentation (ρ = −0.671, P < 0.001; ρ = −0.612, P = 0.002, respectively). The number of HCF was significantly smaller in VKH disease–affected eyes with SGF (median, interquartile range; 134.6, 110.0–159.2) than in those without SGF (229.0, 197.0–261.0) and the eyes of normal controls (211.8, 190.3–233.4).ConclusionsHCF distributions correlated with the degree of fundus pigmentation in eyes with VKH disease. Quantitative measurements of HCF on en face OCT images can be a novel tool in evaluating choroidal pigmentation in patients with VKH disease.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi–Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

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.

This issue of ACTA

This issue of ACTA

Outcomes of initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease occurred during pregnancy.

To investigate the outcomes of initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease that occurred during pregnancy. This is a retrospective case series. During the period between January 2001 and December 2021, we identified 112 patients with initial-onset acute uveitis associated with VKH disease, 67 (59.8%) were females. Among the female patients, 10 (14.9%) patients (20 eyes) were pregnant. Of these patients, 5 patients presented in the first trimester, 3 in the second trimester and 2 in the third trimester. The follow-up period ranged from 8 to 108months (mean 35.2 ± 28.3months). At presentation, 8 (80%) patients had initial-onset acute VKH disease with anterior segment (AS) inflammation and 2 (20%) initial-onset acute VKH disease without AS inflammation. All patients were initially treated with systemic corticosteroids combined with cyclosporine. During follow-up period, none of the patients with initial-onset acute VKH disease without AS inflammation developed any complications. Complications including "sunset glow fundus" in 8 (40%) eyes, cataract in 2 (10%) eyes and subretinal fibrosis in 1 (5%) eye were recorded in patients with initial-onset acute VKH disease with AS inflammation. Four (40%) patients developed pregnancy-related complications, including abortion in 1 patient, systemic hypertension in 1 patient and premature rupture of membrane in 2 patients. There were no documented congenital anomalies in all born babies. Best-corrected visual acuity of ≥ 20/20 was achieved in 16 (80%) eyes at the final follow-up. Primary treatment with combined systemic corticosteroids and cyclosporine in initial-onset acute uveitis associated with VKH disease was safe and effective.

Possible Association between Vogt-Koyanagi-Harada Disease and Coronavirus Disease Vaccine: A Report of Four Cases

ABSTRACT Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune, multisystemic disease characterized by severe bilateral granulomatous posterior, which can occur due to viral infection or vaccination. We report four cases that had a likely association between VKH disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Two patients had VKH symptoms within 1 and 2 weeks after receiving the ChAdOx1 nCoV-19 vaccine. One patient presented with VKH symptoms 5 days after receiving the BNT162b2 vaccine, and one patient had symptoms within 4 weeks after receiving the CoronaVac vaccine. Early diagnosis and treatment of VKH disease are essential for the visual prognosis of this aggressive disease. Further in-depth studies are necessary to investigate this likely association to enable ophthalmologists to identify new assumed correlations between the diseases described in this study.

Correlation between serum immunoglobulin levels and retinal structure in patients with newly diagnosed Vogt‑Koyanagi‑Harada disease.

Immunoglobulins serve immunomodulatory roles in numerous autoimmune diseases. The aim of the present study was to investigate the correlations between serum Ig levels and retinal structural parameters in patients with newly diagnosed acute Vogt-Koyanagi-Harada (VKH) disease. A total of 138 participants were enrolled and the foveal thickness (FT), serous retinal detachment (SRD), sensory retinal thickness, central FT (CFT), cube volume (V) and cube average thickness (AT) were assessed by optical coherence tomography. The patients were divided, according to the extent of SRD, into a high-detachment group (>500 µm) and a low-detachment group (≤500 µm). Rate-scattering turbidimetry was performed to measure the Ig levels. The high-detachment group comprised 51 (36.96%) patients. The proportion of males was significantly greater in the high-detachment group compared with the low-detachment group (58.82 vs. 40.23%; P<0.05) and best-corrected visual acuity was significantly worse in the high-detachment group compared with the low-detachment group (P<0.001). The IgE levels in the high-detachment group were significantly greater compared with the low-detachment group (P<0.05). FT, SRD, CFT, V and AT were significantly greater in the high-detachment group compared with the low-detachment group (P<0.001). The IgE levels were positively associated with SRD, CFT and AT (P<0.05). Multivariate binary logistic regression analysis demonstrated that male sex (B=2.447; P<0.05) and serum IgE levels (B=0.997, P<0.05) may be independent risk factors for severe SRD. The results of the present study demonstrated that males are more likely to develop severe SRD and that serum IgE levels were associated with the extent of detachment. These data suggested that IgE may be involved in the progression of VKH disease.

Identification of immune hub genes participating in the pathogenesis and progression of Vogt-Koyanagi-Harada disease.

BackgroundVogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.MethodsHigh throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.ResultsA total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.ConclusionSix immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.

Outcomes of patients with acute Vogt-Koyanagi-Harada disease treated with intravenous corticosteroid pulse followed by the slow tapering of oral corticosteroid therapy.

To elucidate the intravenous corticosteroid pulse treatment outcomes of patients with acute Vogt-Koyanagi-Harada (VKH) disease and assess the differences between patients with no inflammation worsening and those with persistent or worsening inflammation. Potential factors responsible for eyes with low visual outcomes were also investigated. We retrospectively reviewed the clinical records of patients with acute VKH disease who first visited us between 2009 and 2018 and were followed up for > 300days. Clinical characteristics, treatments, and posttreatment conditions were assessed. Patients were classified into no inflammation worsening (acute-resolved [AR]) and inflammation worsening (chronic-recurrent [CR]) groups based on conditions after 6months from disease onset. This study included 60 eyes from 30 patients (mean age: 52.7years). Patients were treated with methylprednisolone pulse followed by the slow tapering of oral prednisolone; 73% of patients developed AR and 27% CR, and the best-corrected visual acuity (BCVA) was ≥ 1.0 in 83% of eyes at 6months following the introduction of treatment. Although the total prednisolone dose was higher in patients with CR disease, no significant difference was noted in the final BCVA. Among the patients, five eyes had a final BCVA of ≤ 0.5 due to anisometropic amblyopia, diabetic maculopathy, pre-existing macular hole, epiretinal membrane, and ellipsoid zone loss. Patients with acute VKH disease treated with corticosteroid pulse appear to demonstrate good visual outcomes, including patients with CR; the majority of eyes with low visual outcomes have pre-existing conditions that explain the low vision.

A Study of Ocular Manifestations in Pregnancy Induced Hypertension in a Tertiary Healthcare Centre

Pregnancy Induced Hypertension (PIH) is a perplexing taint in the obstetrics field. Visual symptoms occur in up to 25% of these patients. Ocular manifestations include blurring of vision, sudden inability to focus, photopsia,etc. Aim: To determine the ocular manifestations of PIH, create awareness and promote the need of ophthalmic consult for early diagnosis and optimum feto-maternal care in these patients. Settings and Design: A cross‐sectional study was done by recruiting PIH patients admitted in Obstetrics and Gynaecology department as the subjects, after obtaining ethical approval from the institute and informed consent from the patients. Methods: 100 PIH patients aged 18-35 years who were admitted in Obstetrics and Gynaecology department over a period of 3 months were included in this study. Detailed ophthalmic examination was done and findings recorded. Statistical Package for Social Sciences (SPSS V 26.0, IBM) was used for statistical analysis. P value &lt;0.05 was considered significant. Results: Twenty six(26%)patients had previous history of PIH. Chloasma was seen in eight(8%) patients. 32(32%) patients experienced blurring of vision. Anaemic retinopathy was seen in six patients(6%), grade I hypertensive retinopathy changes were seen in nine patients(9%), grade II hypertensive retinopathy changes were seen in four patients(4%), early papilloedema was seen in one patient(1%) and early Vogt-Koyanagi- Harada disease was seen in one patient(1%). Conclusion: Patient counselling and regular ophthalmic consults are necessary for allaying fears and providing optimum visual care to these patients.

Commentary: Dexamethasone intravitreal implant therapy in Vogt-Koyanagi-Harada disease.

Commentary: Dexamethasone intravitreal implant therapy in Vogt-Koyanagi-Harada disease.

Bilateral Iris depigmentation, transillumination defects and hypotony in Vogt-Koyanagi-Harada disease.

Bilateral Iris depigmentation, transillumination defects and hypotony in Vogt-Koyanagi-Harada disease.

Bacillary layer detachment in a patient with serpiginoid choroiditis.

Bacillary layer detachment in a patient with serpiginoid choroiditis.