A case report: co-occurrence of probable Vogt-Koyanagi-Harada disease and diabetic retinopathy.

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.

[Literature data mining on the current research status of uveitis in China].

Objective: To analyze the current research status of uveitis in China. Methods: It was a bibliometric analysis study. Using search formulas covering uveitis and its multiple subtypes, uveitis-related literature in English with publication dates from 2013 to 2022 was retrieved in Web of Science core databases through certain search strategies. This study used the latent Dirichlet allocation (LDA) algorithm to build topic models and analyzed the trends of research topics in recent years. Bibliometric analysis was used to analyze and visualize the bibliometric indicators (e.g., number of publications, citations, and H-index) of the included literature using tools such as VOSviewer software. Results: Over the past decade, China has published 1 657 papers on uveitis, ranking second globally. However, there is still room for improvement in terms of the H-index (58) and citation (12.28 per publication). Countries such as the USA (43.04%) and the United Kingdom (62.54%) were engaged in more international collaboration. We identified ten optimal LDA topics for uveitis literature in China such as immunotherapy, Behçet's disease, and Vogt-Koyanagi-Harada syndrome. Research on uveitis in China was mostly published in Ocular Immunology and Inflammation (92). Conclusions: China has made remarkable progress in uveitis research. Nonetheless, there is still untapped potential to enhance our global academic influence. It is encouraged to promote international collaborations, harness our expertise in areas like Behçet's disease and VKH syndrome, and publish our scientific achievements in high-impact journals.

Vogt-Koyanagi-Harada disease developed during chemotherapy for Hodgkin lymphoma: a case report.

BACKGROUND: Ocular manifestations are known for non-Hodgkin lymphoma, but are rare for Hodgkin lymphoma. We report a case of Vogt-Koyanagi-Harada (VKH) disease presenting as serous retinal detachment and uveitis in both eyes in a child undergoing chemotherapy for Hodgkin lymphoma. CASE PRESENTATION: The patient was a 7-year-old boy with stage IIB Hodgkin lymphoma (nodular lymphocyte predominant type) who was undergoing chemotherapy, including 2 cycles of the OEPA regimen and 1 cycle of the COPDAC regimen. Two days after the end of the COPDAC regimen, the patient complained of headache and of blurred and decreased vision in both eyes. On the basis of optic symptoms, such as uveitis and serous retinal detachment in both eyes, increased cell counts in cerebrospinal fluid, and positivity for human leukocyte antigen (HLA)-DR4 in peripheral blood cells, incomplete VKH disease was diagnosed. Intravenous treatment with high-dose prednisolone (60mg/m2/day) for 7 days improved both visual acuity and serous retinal detachment and enabled the remains of the COPDAC chemotherapy cycle to be administered. With prednisolone treatment, visual acuity improved from 20/500 to 20/20 in the right eye and from 20/63 to 20/25 in the left eye. Because multiple vitiligo lesions later appeared in the abdomen, complete VKH disease was finally diagnosed. CONCLUSION: The onset of VKH disease occurred during chemotherapy for Hodgkin lymphoma. The patient was HLA-DR4-positive and might have had a predisposition to develop autoimmune diseases, including VKH disease. However, the anticancer drugs administered to this patient have not been reported to cause uveitis. Whether Hodgkin lymphoma triggered the development of VKH remains unclear. Early diagnosis of VKH disease and prompt treatment with high-dose prednisone enabled the patient to maintain good visual function despite chemotherapy for Hodgkin lymphoma.

Vogt-Koyanagi-Harada Disease: The Clinical Spectrum and Management of Case Series in a Tertiary Eye Centre in Northern Part Of Malaysia.

AIMS: We present the clinical spectrum, the initial clinical presentation with management trends in treating 14 Vogt-Koyanagi-Harada (VKH) disease cases in a tertiary center in the Northern part of Malaysia. CASE SERIES: There were 14 cases of Vogt-Koyanagi-Harada (VKH) disease retrospectively reviewed over five years (from 2015 to 2020). The mean age at presentation was 37.7 years (range 21-64 years), with female predominance (85.7%). All cases presented with acute uveitic stage and bilateral eye involvement. Of them, 11 (78.6%) were probable VKH, and three (21.4%) were incomplete VKH. All patients attended with acute panuveitis at first presentation. The main posterior segment involvement was disc edema in 57.1% (16 out of 28 eyes) and exudative retinal detachment (ERD) in 35.7% (10 out of 28 eyes). Most of them presented with blindness (3/60 and worse) and moderate visual impair- ment (6/18-6/60); 35.71% each, followed by mild visual impairment (6/12-6/18), and severe visual impairment (6/60-3/60); 7.1% each. Ten patients (71.4%) required combination second-line immunomodulatory treatment during subsequent visits, and only four patients (28.6%) responded well to corticosteroid therapy. Most of the cases achieved no visual impairment (64.3%), followed by mild visual impairment (21.4%) and moderate visual impairment (14.3%), and none were severe or blind at the end of follow-up. CONCLUSION: VKH is a potentially blinding illness if there is inadequate control of the disease in the acute stage. Most of our patients achieved good visual outcomes with early immunomodulatory treatment and systemic corticosteroids.

Proteomic profiling of aqueous humor-derived exosomes in Vogt-Koyanagi-Harada disease and Behcet's uveitis.

Vogt-Koyanagi-Harada (VKH) disease and Behcet's uveitis (BU) are the two major vision-threatening uveitis entities. This study performed the first label-free quantitative proteomics on aqueous humor-derived exosomes from 84 patients with VKH or BU to determine their potential roles. Sixty-five differentially expressed proteins (DEPs) and 40 DEPs were detected in the VKH and BU groups, respectively. GO and KEGG analysis showed that DEPs were mainly enriched in the complement-related pathways. The complement C1q subcomponent subunit B (C1QB) was identified as a key exosomal protein, and its expression was significantly increased by western blotting in both diseases. Additionally, the integrated analysis based on the published scRNA-seq data showed that C1QB-containing exosomes were mainly produced by mononuclear macrophages in the anterior segment tissue. Overall, our proteomic profiling highlights that complement-related pathways may be actively involved in the pathogenesis of these two diseases. These pathways may also serve as treatment targets for both diseases.

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 229 VKH 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 (p Val63Ala) 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.

Reactivation of previously controlled Vogt-Koyanagi-Harada disease more than 46 years following COVID-19 vaccination: a case study.

We report a case of Vogt-Koyanagi-Harada (VKH) disease that recurred 46 years after initial treatment. A 59-year-old woman presented with a 2-month history of bilateral vision blurring. She had received her third dose of coronavirus disease 2019 (COVID-19) vaccination 4 months before the onset of blurring. The best-corrected visual acuity (BCVA) was 1.0 in the right eye and 0.15 in the left eye at the initial visit. Iritis and synechia were observed between the lens and iris bilaterally. A sunset glow fundus was found in both eyes with no serous retinal detachments or disc hyperemia. The patient had a history of VKH disease and had been treated with whole-body corticosteroid administration at another hospital when she was 13 years old. The patient was diagnosed with VKH disease recurrence, and oral corticosteroid therapy and corticosteroid eyedrop treatment were initiated. The treatment response was good. At the time of this writing, recurrence had not been observed for 14 months, and the BCVA was 1.0 in both eyes. To our knowledge, this case represents the longest recorded interval of VKH disease recurrence in the literature to date. COVID-19 vaccination might be the cause of long-term well-controlled disease recurrence.

Characteristics of Ocular Inflammatory Side Effects Associated with Immune Checkpoint Inhibitors in a Northern California Population.

PURPOSE: To characterize the ocular inflammatory side effects associated with immune checkpoint inhibitor (CPI) treatment in a Northern California population. DESIGN: Retrospective case series. PARTICIPANTS: Patients receiving CPI within an integrated healthcare delivery system. METHODS: All patients within Kaiser Permanente Northern California receiving CPI between January 1, 2012 and November 1, 2018 were identified. Medical records of those seen in the ophthalmology clinic at least once were retrospectively reviewed. MAIN OUTCOME MEASURES: Type and duration of ocular inflammation, indication for and exposure to CPI, time from exposure to diagnosis of ocular inflammation. RESULTS: 31 cases of ocular inflammation were identified in 5061 patients (0.61%) receiving CPI. Mean ± SD age was 67 ± 11.9 (range 38-89). Mean time from exposure to diagnosis was 6.8 ± 5.5 months (range 0.5-17). 87% of cases were bilateral, and 43% of cases were chronic. Average ophthalmology follow-up was 16 ± 18 months (range 0-71). 16/31 (52%) had anterior uveitis, 7/31 (23%) had serous retinal detachment or panuveitis resembling Vogt-Koyanagi-Harada syndrome, 4/31 (13%) had papillitis, and 6/31 (19%) had diplopia or ocular motility defect. There was one case each (3.2%) of melanoma associated retinopathy, corneal edema, granulomatous lacrimal gland enlargement, and choroidal neovascularization. CONCLUSIONS: Ocular inflammation is a rare immune associated side effect of CPI treatment, the most common manifestation of which is anterior uveitis.

Epidemiology of Pediatric Uveitis.

Uveitis is uncommon in children and its diagnosis and treatment are challenging. Little is known of the epidemiology of pediatric uveitis. Indeed, population-based studies in the literature are rare. However, there are many tertiary referral center reports that describe the patterns of uveitis in childhood, although few are from developed countries, and their comparison presents some issues. Anterior uveitis is the most frequent entity worldwide, especially in Western countries, where juvenile idiopathic arthritis is diffuse. Most cases of intermediate uveitis do not show any association with infectious or noninfectious systemic diseases. In low- and middle-income countries, posterior uveitis and panuveitis are prevalent due to the higher rates of infectious etiologies and systemic diseases such as Behçet disease and Vogt-Koyanagi-Harada disease. In recent decades, idiopathic uveitis rate has decreased thanks to diagnostic improvements.

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-1ß, 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.

Identification of FCER1G as a cyclosporin A plus corticosteroid sensitization gene in female patients with Vogt-Koyanagi-Harada disease.

The resistance development of the combination regimen of corticosteroids (CS) with cyclosporin A (CsA) leads to therapeutic failure of some patients with autoimmune diseases. In the male patients with Vogt-Koyanagi-Harada (VKH) disease, we have identified RPS4Y1 as an important resistance gene of the regimen and a functional mediator of chlorambucil (CLB). However, it remains unclear what is responsible for the resistance in female patients. In the present study, we performed RNA sequencing, tandem mass tag (TMT) proteomics, gain- and loss-of-function assays and rescue assays to screen and validate potential resistant mediators. The results showed that only Fc epsilon receptor Ig (FCER1G) exhibited significantly differential expression in CD4+ T cells among female CsA & CS resistant, sensitive and CLB & CsA & CS treated patients at transcription and protein levels. Inhibition of FCER1G was demonstrated to modulate CD4+ T cell resistance to CsA & CS in female patients. Importantly, the inhibition was mediated by elevated DNA methylation in the promoter region of the FCER1G gene. Moreover, we found that the salvage effect of CLB on CsA & CS resistance was mediated by an increased FCER1G expression via DNA demethylation in female patients. Taken together, the downregulation of FCER1G due to DNA hypermethylation is responsible for the resistance to CsA & CS and CLB reverses this resistance by inducing FCER1G expression via DNA demethylation in female patients. Modulation of FCER1G would be a promising sensitization strategy in female patients with resistance to CsA & CS.

Polyautoimmunity manifest as inflammatory myopathy, uveitis, and progressive cutaneous depigmentation in a mixed breed dog: a case report.

BACKGROUND: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy. CASE PRESENTATION: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy. The latter progressed to myositis of lingual, pharyngeal, and masticatory muscles confirmed by biopsy. Temporalis muscle was completely replaced by adipose and fibrous tissue, and necrotic myofibers with extensive infiltration of mononuclear cells indicated active myositis of lingual muscle. Skin biopsies showed severe melanin clumping in epidermis, hair follicles, and hair shafts, and perifollicular pigmentary incontinence. Uveitis, depigmentation, and myositis affecting the masticatory, pharyngeal, and tongue muscles were diagnosed based on clinical, histological, and laboratory findings. CONCLUSIONS: To the authors' knowledge, this is the first report of concurrent uveitis, progressive cutaneous depigmentation, and inflammatory myopathy in a dog.

Plasma-Derived Small Extracellular Vesicles From VKH Patients Suppress T Cell Proliferation Via MicroRNA-410-3p Modulation of CXCL5 Axis.

Purpose: Circulating exosomes regulate immune responses and induce immune tolerance in immune-mediated diseases. This study aimed to investigate the role of circulating small extracellular vesicles (sEVs) derived from patients with Vogt-Koyanagi-Harada (VKH) syndrome, in T-cell responses. Methods: The sEVs were isolated from the plasma of healthy controls, patients with VKH, and other uveitis patients. The effects of autologous and allogeneic sEVs on the proliferation of circulating CD4+ T cells were evaluated. Microarray analysis of sEVs was performed to determine their differential miRNA expression profiles. The target genes of the candidate miRNA were predicted and verified. The role of both the candidate miRNA and target genes in T-cell proliferation was tested. Results: Plasma-derived sEVs from patients with VKH inhibited the proliferation of autologous CD4+ T cells. Among all the miRNAs that might be associated with inflammatory activity, we found that miR-410-3p had the largest number of T-cell proliferation target genes. MiR-410-3p mimics inhibited the proliferation of Jurkat cells and CD4+ T cells. C-X-C motif chemokine ligand 5 (CXCL5) was confirmed to be a potential target gene of miR-410-3p, and siRNA-mediated CXCL5 knockdown inhibited cell proliferation. Conclusions: Circulating sEVs exert an inhibitory effect on autologous CD4+ T cells mediated by miR-410-3p by targeting CXCL5, supporting the possibility of using autogenic sEVs to inhibit ocular inflammation.

Therapeutic Effects of Upadacitinib on Experimental Autoimmune Uveitis: Insights From Single-Cell Analysis.

Purpose: This study aimed to elucidate the impact of upadacitinib, a Janus kinase 1 (JAK1)-specific inhibitor, on experimental autoimmune uveitis (EAU) and explore its underlying mechanisms. Methods: We utilized single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to investigate the JAK/signal transducer and activator of transcription (STAT) pathway in peripheral blood mononuclear cells (PBMCs) of 12 patients with Vogt-Koyanagi-Harada (VKH) disease and cervical draining lymph node (CDLN) cells of EAU. After treating EAU with upadacitinib, we analyzed immune cell gene expression and cell-cell communication by integrating scRNA data. Additionally, we applied flow cytometry and western blot to analyze the CDLN cells. Results: The JAK/STAT pathway was found to be upregulated in patients with VKH disease and EAU. Upadacitinib effectively alleviated EAU symptoms, reduced JAK1 protein expression, and suppressed pathogenic CD4 T cell (CD4TC) proliferation and pathogenicity while promoting Treg proliferation. The inhibition of pathogenic CD4TCs by upadacitinib was observed in both flow cytometry and scRNA data. Additionally, upadacitinib was found to rescue the interferon-stimulated gene 15 (ISG15)+ CD4TCs and CD8 T and B cell ratios and reduce expression of inflammatory-related genes. Upadacitinib demonstrated the ability to inhibit abnormally activated cell-cell communication, particularly the CXCR4-mediated migration pathway, which has been implicated in EAU pathogenesis. CXCR4 inhibitors showed promising therapeutic effects in EAU. Conclusions: Our findings indicate that the JAK1-mediated signaling pathway is significantly upregulated in uveitis, and upadacitinib exhibits therapeutic efficacy against EAU. Furthermore, targeting the CXCR4-mediated migration pathway could be a promising therapeutic strategy.

Analysis of HLA Profiles in 390 Uveitis Cases: Insights into Clinical Presentations.

Objective: This study aimed to explain the associations between different types of uveitis and human leukocyte antigen (HLA)-B27, HLA-DR4, and HLA-DRw53. Methods: A retrospective analysis of 390 uveitis cases was conducted among inpatients and outpatients diagnosed at Weifang Eye Hospital from 2013 to 2016. All 390 patients underwent HLA-B27 examination, and an additional 40 patients underwent examination for HLA-DR4 and HLA-DRw53. Gender, age, corrected visual acuity (CVA), and recurrence frequency were statistically analyzed based on the onset site and etiology classification. Results: Among the 390 enrolled patients, 206 were male, and 183 were female, with ages ranging from 6 to 87 years (mean: 44.2). The disease onset was classified into anterior uveitis (AU), panuveitis (panU), posterior uveitis (PU), and intermediate uveitis in 180, 112, 88, and 10 cases, respectively. HLA-B27 was positive in 94 cases (53 males and 41 females), yielding a positive rate of 24.1%. In AU patients, 80 (44.4%) tested positive for HLA-B27, while 8 (7.1%) panU patients and 6 PU patients (6.8%) were HLA-B27 positive; none of the intermediate uveitis (IU) patients exhibited HLA-B27 positivity. HLA-B27, HLA-DR4, and HLA-DRw53 examinations were performed on 40 patients with binocular uveitis, resulting in 2 HLA-B27 positive cases, 15 HLA-DR4 positive cases, and 20 HLA-DRw53 positive cases, with positive rates of 5%, 37.5%, and 50%, respectively. Among 25 Vogt Koyanagi-Harada (VKH) cases, 1 tested positive for HLA-B27, 22 were positive for HLA-DR4, and 24 were positive for HLA-DRw53, with positive rates of 4%, 88%, and 96%, respectively. No positive HLA-B27, HLA-DR4, or HLA-DRw53 cases were found among the 10 cases of Behcet's disease (BD). Conclusions: Human leukocyte antigens (HLAs) play a significant role in the mechanism of uveitis. HLA-B27 exhibits high diagnostic value in acute AU, while HLA-DR4 and HLA-DRw53 are crucial for diagnosing binocular uveitis, particularly Vogt Koyanagi-Harada (VKH) syndrome. Further investigation is warranted to explore the relationship between HLA-DR4, HLA-DRw53, and uveitis.

[Recurrent chronic Vogt-Koyanagi-Harada syndrome or sarcoidosis? A Gloomy diagnosis]. / ¿Síndrome de Vogt-Koyanagi-Harada crónico o sarcoidosis? Un diagnóstico sombrío.

Background: Vogt-Koyanagi-Harada syndrome (VKH) is a systemic disease that affects organs profuse in melanocytes, presenting with a chronic and diffuse bilateral granulomatous panuveitis, as well as neurological, auditory, and cutaneous manifestations. In this article, a systematic approach is presented for the diagnostic management of VKH syndrome, considering relevant diagnostic possibilities to rule out other entities that manifest similar symptoms. Clinical case: 71-year-old man with a long-standing history of vitiligo, who experienced visual loss in his right eye 6 months before his admission, along with bilateral hearing loss predominantly in the right ear. During his hospitalization, he presented with chronic headache, fever, and significant involuntary weight loss. Ophthalmological examination revealed that his right eye only perceived light and had hyperemic bulbar conjunctiva, while the left eye had a visual acuity of 20/200. The right fundus had scattered pigmentation, while the left had an edematous optic disc and right optic atrophy. Conclusions: The diagnosis of VKH syndrome is established by the presence of the 5 diagnostic criteria for complete disease, including retinal depigmentation, neurological alterations, and dermatological manifestations. Since patients can present with a wide variety of symptoms, initial differential diagnosis should be considered, which represents a diagnostic challenge.

Introducción: el síndrome de Vogt-Koyanagi-Harada (VKH) es una enfermedad sistémica que afecta a órganos ricos en melanocitos y se manifiesta con una panuveítis granulomatosa bilateral, crónica y difusa, así como con manifestaciones neurológicas, auditivas y cutáneas. En este artículo se presenta un enfoque sistemático para el abordaje diagnóstico del síndrome de VKH y se consideran las posibilidades diagnósticas relevantes para descartar otras entidades que se presentan con síntomas similares. Caso clínico: hombre de 71 años con antecedentes de vitiligo de larga data, quien experimentó una pérdida visual en su ojo derecho seis meses antes de su ingreso, junto con hipoacusia bilateral, predominantemente en el oído derecho. Durante su hospitalización, presentó cefalea crónica, fiebre y una significativa pérdida involuntaria de peso. En la exploración oftalmológica, el ojo derecho solo percibía luz y presentaba conjuntiva bulbar hiperémica, mientras que el ojo izquierdo tenía una agudeza visual de 20/200. El fondo del ojo derecho presentaba pigmentación dispersa, mientras que el izquierdo tenía una papila edematosa y atrofia óptica derecha. Conclusiones: el diagnóstico del síndrome de VKH se establece mediante la presencia de los 5 criterios diagnósticos para la enfermedad completa, incluida la hipopigmentación retiniana, las alteraciones neurológicas y las manifestaciones dermatológicas. Dado que los pacientes pueden presentar una amplia variedad de síntomas, el diagnóstico diferencial debe considerarse inicialmente, lo que representa un desafío diagnóstico.

VOGT-KOYANAGI-HARADA DISEASE-LIKE UVEITIS IN A PATIENT WITH ADVANCED MELANOMA TREATED BY SEQUENTIAL ADMINISTRATION OF NIVOLUMAB AND DABRAFENIB/TRAMETINIB THERAPY.

PURPOSE: To describe a case of bilateral Vogt-Koyanagi-Harada (VKH)-like uveitis during treatment with dabrafenib and trametinib and three months after discontinuation of nivolumab for malignant melanoma, and discuss the possible (synergistic) role(s) of mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors in its pathophysiology. METHODS: Retrospective case report with fluorescein angiography and optical coherence tomography. RESULTS: A 55-year old patient with metastatic melanoma presented with a complaint of gradually worsening blurry vision in the right eye during treatment with dabrafenib and trametinib, three months after discontinuation of nivolumab. Based on the clinical examination, optical coherence tomography and fluorescein angiography findings, and a thorough laboratory work-up, he was diagnosed with a bilateral VKH-like uveitis without extraocular manifestations. The uveitis responded well to oral corticosteroids. CONCLUSION: Vogt-Koyanagi-Harada-like uveitis is a rare adverse effect of MAPK inhibitors and immune checkpoint inhibitors. Similar pathogenetic mechanisms including a drug-induced autoimmunity targeted against benign and malignant melanocytes may underlie MAPK inhibitor-induced and immune checkpoint inhibitors-induced VKH-like uveitis. In our report, the patient developed a VKH-like uveitis during MAPK inhibition therapy, four months after discontinuation of nivolumab. It is difficult to delineate whether MAPK inhibition alone was responsible for this adverse effect, or whether, on the contrary, potentiation occurred as a result of immune modulation by previous treatment with an immune checkpoint inhibitor. Further cases are needed to further clarify this latter hypothesis.