Vogt-Koyanagi-Harada Research Articles

METHOTREXATE FOR REBOUND PHENOMENON OF VOGT-KOYANAGI-HARADA IN JUVENILE: A RARE CASE REPORT

Introduction: Vogt-Koyanagi-Harada (VKH), an auto-immune disorder driven by melanocyte antigen, is rare in children. The mainstay treatments are corticosteroid and immunomodulators. Methotrexate is one of immunomodulator that widely used due to its effectiveness with minimal side effects. Case Report: A 9-years-old boy get diagnosed Vogt-Koyanagi-Harada. His best corrected visual acuities (BCVA) were 20/400 in both eyes. Anterior segment examination showed granulomatous uveitis. Posterior segment examination revealed optic disk swelling, Dallen Fuch’s nodule and exudative retinal detachment. We also found poliosis and vitiligo in his lips. He had been previously treated with topical corticosteroids, oral corticosteroids and topical cycloplegics. The dose was tapered every month. After taking medication for 5 months with the last dose oral corticosteroid 16 mg/day and topical corticosteroid every 8 hours, his BCVA recovered to 20/25 RE and 20/40 LE. During the treatment time, the patient discontinued the medication due to parental disobedience and then came with decrease of vision. Based on the consideration of rebound phenomenon and the use of maximum dose of corticosteroids, we consulted the patient to the pediatrician, and decided to give methotrexate as an immunosuppressant. After receiving 15 mg/week of methotrexate for 3 months, inflammation calmed down but unfortunately the vision did not improve. Discussion: In children, the main treatment for VKH disease is high-dose corticosteroids. Considering the side effects of prolonged systemic corticosteroid therapy, methotrexate become the first line of corticosteroid sparing agent, especially in chronic stage. Conclusion: Methotrexate can be an effective treatment option for rebound VKH. Keywords: Juvenile Vogt-Koyanagi-Harada, Steroid Sparing Agents, Rebound Phenomenon, Methotrexate.

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

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. 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. VKH is a potentially blinding illness if there is inadequate control of the disease in the acute stage. Most of our patients achievedgood visual outcomes with early immunomodulatory treatment and systemic corticosteroids.

A Unique Case of Acute Deterioration in Visual Acuity: Vogt-Koyanagi-Harada Disease

Vogt-Koyanagi-Harada (VKH)disease is a chronic autoimmune inflammatorydisorderwithmultisystem involvement particularly involving the eye, skin, ear and brain. Our patient reported in the Ophthalmology OPD, CMH, Lahore, a 41-year-old female patient who presented with decreased visual acuity of 6/9 and 6/18 in her right and left eye respectively with intermittent tinnitus. Aslit lamp examination revealed bilateral paramacular choroiditis, more pronounced in the left eye. Fundoscopy showed the 'sunset glow fundus.' HerOCTshowedslightflattening ofthe foveal contourinthe left eye withgeneralized foveal thinning while the right eye had parafoveal thickening with a foveal lamellar hole. FFA showed a serous detachment in herleft eye.Adiagnosis of bilateral incomplete Vogt-Koyanagi-Harada syndrome was made as she tested negative for infectious diseases. She was started on an oral course of steroids initially but after persistent episodic exacerbations ciclosporin 75mg twice daily was started and regular 2 weekly follow-ups were advised. The mainstay of treatment for Vogt–Koyanagi–Harada disease is systemic corticosteroid therapy but the refractory cases get additional immunosuppressants like ciclosporin which was required in our patient as well. Keywords: Autoimmune, Fovea, Visual acuity.

VKH disease in the elderly: Variations in clinical course as compared to VKH disease in adults.

To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) disease in elderly patients. Retrospective analysis of patients older than 50 years with VKH disease at two referral centers in India. Demographics, extraocular and ocular involvement, treatment, complications, and visual acuity outcomes were noted. In total, 69 patients (mean age at presentation: 56.4 ± 4.7 years) were analyzed; 6/69 patients had diabetes mellitus at presentation, and 10/69 had hypertension. Clinical signs included anterior chamber cells >2+ (29%), granulomatous keratic precipitates (23%), disc hyperemia (26%), neurosensory retinal detachment (34.7%), and "sunset-glow" fundus (52.1%). Patients were classified as probable (n = 50, 72.4%), incomplete (n = 18, 26%), and complete VKH (n = 1, 1.4%). The mean follow-up period was 20.2 ± 19.4 months. Improvement in mean BCVA of (0.63 LogMAR, 6 Snellen lines) was noted on the last follow-up. Patients receiving systemic steroids with immunosuppressants ( P < 0.0001) had better visual outcomes at final follow-up compared to steroids alone ( P = 0.103). Eight patients (11.6%) had complications due to systemic immunosuppressants, and 17 patients (24.6%) developed diabetes mellitus or had worsening of diabetes while on systemic corticosteroids. Few patients presented with systemic manifestations in our cohort. Those treated with steroids and concurrent immunosuppressants had better outcomes. However, therapy with immunosuppressants was encountered with major dose-limiting complications in a significant number of elderly patients with VKH syndrome.

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 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.

Vogt–Koyanagi–Harada-like presentation: A short case series

We report a short case series of Vogt–Koyanagi–Harada (VKH)-like presentation in the eyes of Indian patients following vaccination. Patients with symptoms and signs of VKH that developed after coronavirus disease 2019 (COVID-19) vaccination, who presented with the first episode of the disease were included. There were five patients with four probable VKH and one incomplete VKH, with the mean time of onset being 5.4 ± 3.7 weeks. All patients had bilateral presentation. Steroid treatment was effective with no recurrence. Any vaccination can act as a trigger for the first episode of VKH presentation, and patient education on the same is needed.

Vogt‐Koyanagi‐Harada‐like findings as the first manifestation of neuroleukaemia

Aims/Purpose: To report a well‐documented case of a 62‐year‐old woman presenting with VKH‐like findings as the first manifestation of neuroleukaemia.Methods: Case study.Results: A 52‐year‐old woman who had received a diagnosis of acute myeloid monoblastic leukaemia (AML) one month prior and was in remission after the induction phase presented with floaters and gradual visual loss in both eyes. Visual acuity was 20/200 and 20/25, respectively. Anterior segment exam was normal in both eyes. Funduscopy showed reduced foveal reflex. On spectral‐domain OCT, subretinal fluid was found in both eyes. Fluorescein angiography showed hypofluorescent areas compatible with multifocal serous retinal detachments and multiple hyperfluorescent dots surrounding the detached areas. Days after, the patient debuted with facial palsy and binocular diplopia due to bilateral VI cranial nerve (CN) palsy, left VII CN palsy and right complete III CN palsy. An MRI was performed with no signs of infiltration. A cerebrospinal fluid sample was drawn by lumbar puncture and its analysis denoted infiltration of AML cells with similar immunophenotype to that on initial bone marrow biopsy. Our patient presented with an atypical case of Vogt‐Koyanagi‐Harada (VKH) with multiple leakages along the periphery of the detached retinal area. This sparing of the macula should be considered a suspicious pattern, and combined with the finding of CN palsies was enough to suspect a relapse in the form of CSF infiltration, making the diagnosis of neuroleukaemia possible.Conclusions: Exudative retinal detachment can be a primary presentation of AML or denote a relapse. VKH is a diagnosis of exclusion, as one of the main criteria for its diagnosis is the absence of other systemic diseases. This becomes especially important in atypical presentations and older patients. So as not to miss life‐threatening underlying conditions, leukaemia and lymphoma should be considered in the differential diagnosis of VKH.

RWC Update: Improving Surgical Outcomes With Intraoperative Fluorescein Angiography; Myopic Macular Holes - When to Operate?; Harada's Disease.

RWC Update: Improving Surgical Outcomes With Intraoperative Fluorescein Angiography; Myopic Macular Holes - When to Operate?; Harada's Disease.

Retinal oximetry in vascular diseases

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of haemoglobin. The imaging technology is non‐invasive and reproducible with remarkably low variability on test–retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic disease. The aim of this presentation is review of state of the art knowledge of us of retinal oximetry in vascular diseases and its possible clinical application.In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment.Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular oedema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia.Retinal oxygen metabolism is altered in uveitis associated with VKH disease. Oxygen saturation profile is abnormal in acute uveitic phase of the disease and returns to normal in those who recover with normal fundus appearance, but not in eyes that suffer permanent anatomical damage with “sunset glow fundus” and chorioretinal atrophy. Retinal oximetry may be of value in evaluating vascular and metabolic aspects of posterior uveitis.

Vogt-Koyanagi-Harada disease and bilateral simultaneous Adie’s pupil

Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon autoimmune inflammatory malady commonly accompanied by neurological, auditory, and integumentary signs. We report a case of a teenage girl who complained of persistently decreased vision for the last 15 days. There was no systemic association. After 2 weeks, the patient developed tonic pupils. The pupil showed a tonic response to a 0.125% pilocarpine eye drop. Upon examinations, the patient was diagnosed with Vogt-Koyanagi-Harada disease and bilateral Adie’s pupil, which is a rare conditions associated with VKH disease. Early treatment is crucial for preserving vision.

Evaluation of the Activity of Vogt–Koyanagi–Harada Disease; A Comparison of Indocyanine Green Angiography Scoring, Enhanced Depth Imaging Optical Coherence Tomography, and Choroidal Vascularity Index

Abstract Purpose: To investigate the correlation between choroidal biomarkers using enhanced depth imaging optical coherence tomography (EDI-OCT) and indocyanine green angiography (ICGA) scoring for monitoring the activity of Vogt–Koyanagi–Harada (VKH). Methods: Patients who were not in the acute phase of VKH were recruited. Simultaneous EDI-OCT and ICGA were captured in seven patients only at baseline, in six patients at the 3-month follow-up, and in two patients at both the 6- and 9-month follow-ups. Subfoveal choroidal thickness (SFCT), subfoveal choroidal area (SFCA), and choroidal vascular index (CVI) were measured on EDI-OCT using FIJI software and a denoising system. ICGA scoring was performed. Results: Fifteen subjects with the median of 4-month follow-up were recruited. Forty-eight pairs of EDI-OCT and ICGA were investigated. In univariate analysis, ICGA scores were positively associated with SFCT, and SFCA, but negatively with CVI. The strength of correlation between ICGA scores and SFCT was strong (correlation coefficient: 0.91). In multivariate analysis, only SFCT remained significant (B: 2.4, 95% confidence interval: 1.9–3.0; P &lt; 0.001). Conclusions: SFCT can be an acceptable representative of the subclinical inflammatory activity of VKH. As an alternative to ICGA, SFCT functions better than SFCA and CVI.

Cabozantinib-Associated Exudative Retinal Detachment and Choroiditis: A Case Report

Abstract Purpose: To describe the first reported instance of an acute chorioretinal inflammatory response to cabozantinib. Methods: Case report. Results: A 54-year-old Asian male presented with blurred vision 2 weeks following the commencement of cabozantinib for metastatic renal cell carcinoma. Ophthalmic examination revealed bilateral exudative retinal detachments and choroiditis in a pattern similar to Vogt–Koyanagi–Harada disease. Further investigations revealed latent tuberculosis (TB), and management of this ocular adverse event was with cabozantinib cessation, high-dose oral prednisone, single-agent anti-TB therapy, and methotrexate. Return of visual function and ocular anatomy occurred within 1 month. Conclusions: Modern pharmacotherapy for metastatic cancer may increase survival, but a range of ocular and systemic adverse events are frequently seen. Screening and early intervention can mitigate adverse events and treatment burden, while maximizing benefits for this disadvantaged patient group.

Intravitreal bevacizumab in choroidal neovascularisation in Vogt‐Koyanagi‐Harada disease in a child: A review of literature

Aims/Purpose: Interest of bevacizumab in children in the treatment of choroidal neoplasms in Vogt Koyanagi Harada syndrome.Methods: In this work we report the case of an extra‐foveal choroidal neovascularization in a child followed for VKH syndrome with a good response to intravitreal injections of bevacizumab.Results: We report the case of a 12‐year‐old child who initially presented to the hospital in 2020 for bilateral decreased visual acuity and headache. There was no history of systemic disease. Initial visual acuity was 1/10 in both eyes. Biomicroscopic examination revealed granulomatous retrodescemetic precipitates, 2× anterior chamber tyndall, 1× vitreous tyndall, and bilateral exudative retinal detachment associated with bilateral papilledema in both eyes. Based on these findings, a diagnosis of Vogt‐Koyanagi‐Harada syndrome was made, and treatment was initiated with intravenous, oral, and topical corticosteroids. Visual acuity improved to 6/10 OD and 7/10 OS the following month. The patient was then followed up at the university hospital regularly. After controlling the inflammation, steroids were decreased over a period of 2 years but the patient relapsed at high dose to declare cortico‐dependence. Anti‐TNF alpha was started to control the inflammation and visual acuity remained stable until July 2022. Choroidal neovascularization then developed, reducing the patient's visual acuity to 3/10 in both eyes within 1 month. Fluorescein angiography and macular OCT confirmed the diagnosis of extrafoveolar choroidal neovascularization in both eyes. After obtaining informed consent, intravitreal bevacizumab was injected 3 times at 6 week intervals in each eye. After the 6th injection, the patient's best‐corrected visual acuity improved to 8/10 in the right eye and 10/10 in the left eye. The fundus photograph illustrates the regression of the choroidal neovessels. Fluorescein angiography confirmed the reduction in leakage. Choroidal neovascular membranes can cause severe visual impairment and are a major challenge in the management of patients.Conclusions: This case illustrates that intravitreal bevacizumab has a possible role in the treatment of the disease, with regression of neovascular lesions in the eye.

Multiple sclerosis-associated uveitis - A series from South India.

To report clinical profiles of multiple sclerosis (MS)-associated uveitis in seven cases from a single tertiary eye care center in South India. Retrospective case series 2013-2023. Seven cases of MS-associated uveitis were retrieved from our databases. There were five females and two males. The diagnosis of MS was made by the neurologist in all cases. Bilaterality was seen in all cases. Intermediate uveitis was the most common presentation (five cases). It was associated with peripheral retinal vasculitis (two cases) and disc pallor (two cases). Fuchs heterochromic iridocyclitis (one case) and incomplete Vogt-Koyanagi-Harada (VKH)-like presentation with a peripapillary choroidal neovascular membrane (one case) were the other presentations. In the case with incomplete VKH-like presentation, whole genome sequencing revealed a heterozygous non-synonymous variation (c.1228C>T) in exon 10 of TNFRSF1A, suggestive of susceptibility to multiple sclerosis 5 due to mutation in the TNFRS1A gene on chromosome 12p13.31. All cases received systemic steroids. Azathioprine (three cases) and rituximab (three cases) were the commonly used immunomodulatory drugs. The visual outcome was good in all cases at the last follow-up. MS-associated uveitis is underreported in India. This series highlights the clinical profile of MS-associated uveitis in India.

Demographic and Clinical Characteristics of Uveitis for Adult Patients Attending Mansoura Ophthalmic Center

ABSTRACT Aim The aim of this research is to evaluate the demographic attributes and clinical manifestations of uveitis in adult patients frequenting the Mansoura Ophthalmic Center. Methods Utilizing a cross-sectional, prospective, analytical study design, this research engaged adult patients visiting the outpatient uveitis clinic at the Mansoura Ophthalmic Center. Comprehensive case evaluations involved collecting detailed patient histories, examining ophthalmic records, and conducting thorough ocular examinations. These examinations encompassed the assessment of visual acuity, slit-lamp examination, and fundus examination. Furthermore, selected cases underwent optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Results The Study involved an examination of 411 eyes belonging to 254 uveitic patients. In the Egyptian context, anterior uveitis surfaced as the most prevalent form of uveitis. The average Best-Corrected Visual Acuity (BCVA) among the cases studied was 0.797 ± 0.77 LogMAR, with the majority of cases demonstrating vision superior to 0.3 LogMAR. Notably, the principal causes of vision loss were generally reversible. Macular edema was identified as the leading cause of vision loss, representing 20.7% of cases as evidenced by OCT. The ratio of non-infectious to infectious uveitis stood at 92.2% to 7.8%. The most commonly observed etiologies of non-infectious uveitis included Behçet’s disease (33.3%), Vogt-Koyanagi-Harada (VKH) syndrome (19.7%), idiopathic causes (19.2%), and ankylosing spondylitis (AS) (11.9%). Conversely, the most frequent infectious etiologies were trematode-induced uveitis (2.9%), herpetic uveitis (1.7%), toxoplasmosis (1.5%), tuberculosis (TB) (1.5%), and brucellosis (0.2%). Conclusions This study conclusively indicates that anterior uveitis is the predominant anatomical type of uveitis in Egypt. Further, etiological diagnoses of uveitis should particularly emphasize Behçet’s disease, VKH syndrome, and ankylosing spondylitis.

Prognostic value of pretreatment indocyanine green angiography in the acute uveitic phase of Vogt-Koyanagi-Harada disease.

To investigate the prognostic value of pretreatment indocyanine green angiographic (ICGA) features in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. Retrospective analysis of 84 patients (168 eyes). Main outcome measures were final visual acuity, development of 'sunset glow fundus' (SGF) and progression to chronic recurrent evolution. Thirty-eight patients (76 eyes) presented in the phase preceding anterior segment (AS) inflammation (early presentation) and 46 patients (92 eyes) had AS inflammation at presentation (late presentation). The mean number of hypofluorescent dark dots (HDDs) and frequency of disc hyperfluorescence were more in the late presentation group (p < 0.001 for both comparisons), whereas the early presentation group showed higher frequencies of peripapillary punctate choroidal hyperfluorescence (p < 0.001) and hypofluorescent patches involving macula corresponding to the areas of exudative retinal detachment (p = 0.012). The mean number of HDDs and the frequency of disc hyperfluorescence were higher among eyes that developed SGF (p < 0.001 for both comparisons) and eyes that progressed to chronic recurrent evolution (p < 0.001; p = 0.001, respectively). The frequencies of peripapillary punctate choroidal hyperfluorescence and hypofluorescent patches corresponding to the areas of exudative retinal detachment were less in the eyes that developed SGF (p = 0.019; p = 0.003, respectively). Punctate choroidal hyperfluorescence elsewhere was less frequent in the eyes that developed SGF (p < 0.001) and eyes that progressed to chronic recurrent evolution (p = 0.002). Pretreatment ICGA has a prognostic value in initial-onset acute uveitis associated with VKH disease.

Comparisons of choroidal blood flow velocity between initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy.

Acute central serous chorioretinopathy (CSC) and Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase are characterized by serous retinal detachment caused by dysfunction of the choroid. The aim of this study is to compare blood flow velocity and pulse waveform parameters in the choroid between these two diseases. In this study, 25 patients (50 eyes) with VKH disease, 21 patients (27 eyes) with CSC and 15 healthy controls (30 eyes) were studied. Laser speckle flowgraphy (LSFG) was performed at presentation. Choroidal mean blur rate (MBR), representing blood flow velocity in choroidal vessels, was significantly lower in the eyes affected by VKH disease compared with the healthy control and CSC eyes. CSC eyes had a significantly higher MBR compared with healthy controls. Among the analyzed pulse waveform parameters, blow-out time (BOT), falling rate (FR) and flow acceleration index (FAI) changed significantly. BOT value was significantly lower in CSC eyes than in healthy control and VKH eyes. FR and FAI values were significantly lower in VKH eyes than in healthy control and CSC eyes. There was a strong positive correlation between MBR and FAI. Our findings confirm different pathophysiology of these two diseases. Assessment of choroidal blood flow velocity and haemodynamics with LSFG provides useful information to differentiate acute CSC and initial-onset acute uveitis associated with VKH disease.

Vogt-Koyanagi-Harada disease-like uveitis after drug therapy including BRAF/MEK inhibitors in melanoma patients with HLA-DRB1*04.

The combination of BRAF kinase inhibitors (BRAFis) and MEK kinase inhibitors (MEKis) is one of the most promising chemotherapy regimens in the treatment of BRAF-mutant melanoma. Although BRAFi plus MEKi combined therapy is widely used for the treatment of BRAFV600-mutated melanoma, the incidence of uveitis caused by BRAFi plus MEKi is limited. In this report, we described five cases (two men and three women) of Vogt-Koyanagi-Harada (VKH) disease-like uveitis in melanoma patients who received BRAFi plus MEKi combined therapy. Of note, all the patients had the HLA-DRB1*04 haplotype, which is frequently detected in VKH-like non-infectious uveitis. On the other hand, among BRAFi plus MEKi-treated patients who did not develop VKH disease-like uveitis, only one of five (20%) patients had the HLA-DRB1*04 haplotype. Collectively, BRAFi/MEKi might induce severe VKH disease-like uveitis in melanoma patients with the HLA-DRB1*04 haplotype.

A Case of Vogt-Koyanagi-Harada-like Syndrome Associated with Immunotherapy (Pembrolizumab)

Purpose: To report a case of Vogt-Koyanagi-Harada-like syndrome that occurred during immunotherapy (pembrolizumab) in a patient with non-small-cell lung cancer (NSCLC).Case summary: A 64-year-old female visited our clinic complaining of decreased visual acuity in both eyes. The patient had NSCLC and had been prescribed immunotherapy (pembrolizumab) by the Department of Pulmonology. Fundus examination and optical coherence tomography revealed multiple intraretinal cysts and subretinal fluid in both eyes. After evaluation using fluorescein and indocyanine green angiography, Vogt-Koyanagi-Harada (VKH) disease was diagnosed in both eyes and oral prednisolone 40 mg/day was prescribed for 2 weeks. At an outpatient visit at that time, the symptoms had improved, and fundus examination and optical coherence tomography revealed decreases in the number of intraretinal cysts and the subretinal fluid level. Oral prednisolone was reduced to 20 mg/day for 2 weeks. At an outpatient visit at that time, the symptoms had further improved; no cysts or subretinal fluid were apparent on fundus examination or optical coherence tomography, and only a small amount of subretinal fluid was present near the macula of the right eye.Conclusions: VKH disease may develop during immunotherapy (pembrolizumab) but can be rapidly diagnosed and treated with oral steroids.