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.

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.

iPSC-based model of Vogt-Koyanagi-Harada disease for phenotype recapitulation and drug screening.

Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease.

Management of recalcitrant vitiligo in Vogt-Koyanagi-Harada syndrome: Adjuvant ablative fractional laser.

The course of dermatologic findings in Vogt-Koyanagi-Harada disease is variable. Herein, we report the remarkable repigmentation of widespread facial vitiligo lesions in an adolescent girl with Vogt-Koyanagi-Harada disease. The patient was treated with a combination of fractional erbium:YAG laser, topical tacrolimus, and phototherapy.

Vogt-Koyanagi-Harada disease. Case report and review of the literature / Enfermedad de Vogt Koyanagi Harada. Reporte de un caso y revisión de la literatura

ABSTRACT Vogt Koyanagi Harada disease affects several parts of the body, such as eyes, meninges, ears, and skin. The progressive course of the disease can lead to blindness and deafness. The case is presented of a Hispanic woman (mixed-race) with visual alterations, headache, tinnitus, hearing loss, and posterior uveitis with serous detachments of the retina in both eyes, as well as lymphocytic meningitis. The aim of the present study is to review the literature, the diagnostic strategies, and the appropriate treatment, as well as to update the immunogenetic pathogenesis of the disease.

RESUMEN La enfermedad de Vogt Koyanagi Harada compromete múltiples órganos tales como ojos, meninges, oídos y piel. El curso progresivo de la enfermedad puede llevar a ceguera y cofosis. Se describe un caso de esta enfermedad en mujer hispana (mestiza) con alteraciones visuales, cefalalgia, tinnitus e hipoacusia a quien se le encuentra uveítis posterior con desprendimientos serosos de retina en ambos ojos y meningitis linfocitaria. El objetivo del presente estudio es, mediante una revisión de la literatura, actualizar la patogénesis inmunogenética, conocer las estrategias diagnósticas y el tratamiento apropiado.

Desprendimiento de retina exudativo bilateral asociado con coriorretinopatía serosa central en una paciente tratada con corticoesteroides / Bilateral exudative retinal detachment associated with central serous chorioretinopathy in a patient treated with corticosteroids

Caso clínico: Presentamos el caso de una mujer de 54 años con una coriorretinopatía serosa central diagnosticada erróneamente de enfermedad de Vogt-Koyanagi-Harada y tratada con corticoides sistémicos. La paciente desarrolló un desprendimiento de retina exudativo bulloso en ambos ojos. Discusión: La interrupción del tratamiento con corticoides junto con el drenaje quirúrgico del líquido subretiniano y la aplicación de terapia fotodinámica consiguió la mejoría anatómica y funcional. El correcto diagnóstico de las formas atípicas de la enfermedad podría evitar las complicaciones del uso inadecuado de los corticoides (AU)

Case report: The case is presented on a 54-year-old woman with a central serous chorioretinopathy, misdiagnosed as Vogt-Koyanagi-Harada disease, and treated with systemic corticosteroids. The patient presented with a bilateral bullous exudative retinal detachment. Discussion: Discontinuation of corticosteroid therapy, surgical drainage of subretinal fluid, and photodynamic therapy, led to anatomical and functional improvement. The recognition of an atypical presentation of central serous chorioretinopathy may avoid complications of the inappropriate treatment with corticosteroids (AU)

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation.

AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behçet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-κB p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-κB.

[Bullous retinal detachment in chronic central serous chorioretinopathy treated with photodynamic therapy]. / Desprendimiento de retina bulloso en coriorretinopatía serosa central crónica tratado con terapia fotodinámica.

CASE REPORT: We describe a case of serous retinal detachment as an atypical presentation of bilateral chronic central serous chorioretinopathy, DISCUSSION: We present its differential diagnosis and therapeutical management with low-fluence photodynamic therapy, achieving satisfactory anatomical and functional results.

Blue light and near-infrared fundus autofluorescence in acute Vogt-Koyanagi-Harada disease.

BACKGROUND/AIMS: To investigate the characteristics of fundus autofluorescence (FAF) in acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: FAF photography with blue light (BL-FAF) and near-infrared light (NIR-FAF) was performed on 10 eyes of five patients using a confocal scanning laser ophthalmoscope before and after treatment. The FAF images were followed for 6 months and retrospectively reviewed with comparisons of the other imaging modalities. RESULTS: At presentation, four eyes of two patients who presented soon after the initial ocular symptoms showed mild and uniform hyperautofluorescence in the macula mixed with hypoautofluorescence in the areas of serous retinal detachment. After immediate treatment with an intravenous high-dose steroid, the abnormal FAF returned to normal at 6 months. The other six eyes of three patients, who presented weeks after the symptoms, initially demonstrated diffuse and mottled hyperautofluorescence over the posterior pole, mixed with hypoautofluorescence induced by serous retinal detachment in four eyes. After treatment with an intravenous high-dose steroid, all six eyes showed scattered and widespread hyperautofluorescence, which gradually became evident and concentrated in the macula, partially resulting in some hypoautofluorescent dots at 6 months. The BL-FAF and the NIR-FAF demonstrated similar FAF patterns, but more evidently in NIR-FAF. CONCLUSION: FAF photography non-invasively visualised sequential metabolic and functional changes in the retinal pigment epithelium (RPE) in acute VKH disease. The results suggest that early and sufficient treatment with a high-dose steroid might prevent persistent RPE damage. In addition, NIR-FAF can be an alternative method for the early detection of RPE abnormality.

A case of Vogt-Koyanagi-Harada disease in a patient with Graves disease.

A case of Vogt-Koyanagi-Harada disease (VKH) that developed in a 36-year-old woman with Graves' disease was described. The patient was treated with Lugol's solution and presented with bilateral serous retinal detachment. She had also suffered from methimazole-induced hypersensitivity and steroid-induced myopathy. Fluorescein angiography showed multiple leakage points and a lumbar puncture revealed pleocytosis, which was compatible with VKH. High dose steroid pulse therapy was successful. Altered immune regulation associated with drug-induced hypersensitivity may contribute to the development of VKH in patients with Graves' disease.

A Case of Vogt-Koyanagi-Harada Disease in a Patient With Graves Disease

A case of Vogt-Koyanagi-Harada disease (VKH) that developed in a 36-year-old woman with Graves' disease was described. The patient was treated with Lugol's solution and presented with bilateral serous retinal detachment. She had also suffered from methimazole-induced hypersensitivity and steroid-induced myopathy. Fluorescein angiography showed multiple leakage points and a lumbar puncture revealed pleocytosis, which was compatible with VKH. High dose steroid pulse therapy was successful. Altered immune regulation associated with drug-induced hypersensitivity may contribute to the development of VKH in patients with Graves' disease.

Atypical Vogt-Koyanagi-Harada Syndrome in a 7-Year-Old Boy

PURPOSE: Vogt-Koyanagi-Harada syndrome is more common in adults than in children. We report a atypical case of Vogt-Koyanagi-Harada syndrome like white dot syndromes in a 7-year-old child. METHODS: A 7-year-old child visited with complaints of decreased binocular visual acuity. Under ophthalmologic examination, anterior uveitis and optic neuropathy were found. But there was no other retinal lesion. After high-dose intravenous corticosteroids pulse therapy, yellow pigment lesions like white dot syndromes developed in peripheral retina and enlarged without serous retinal detachment. RESULTS: In 5 months after high-dose intravenous corticosteroids pulse therapy, anterior inflammation was decreased and visual acuity was 0.8 in both eyes. But depigmented retinal lesions were increased and sunset glow occurred. Alopecia and poliosis of hair were found. Human leukocyte antigen typings revealed HLA-DR4 antigen.

[Therapeutic regimen in Vogt-Koyanagi-Harada syndrome].

OBJECTIVE: To compare the effectiveness of therapeutic regimen in Vogt-Koyanagi-Harada (VKH) syndrome and determine the reasonable regimen for different patients. METHODS: Data of 82 patients with VKH syndrome, coming from all over China and referred to Zhongshan Ophthalmic Center from January 1996 to December 2000 were retrospectively analyzed. Twenty-eight patients (56 eyes) with first attack of the intraocular inflammation were treated with oral prednisone for more than one year, whereas 54 patients (108 eyes) with recurrent episodes were treated with chlorambucil for more than one year. All patients were treated with a combination of these immunosuppressives with traditional Chinese medicine herbs, and followed up more than one year after systemic treatment. The previous treatment for these 54 patients was also analyzed in an attempt to compare these results with those presented here. RESULTS: Uveitis was completely controlled in 96.4% of the patients treated with oral prednisone, and all of these patients showed improved vision after treatment. A complete control of uveitis was achieved in 94.4% and improved vision was seen in 88.0% of the patients treated with chlorambucil. All of these 54 patients, although treated with longer but intermittent systemic corticosteroids before installation of chlorambucil, showed a chronic or recurrent uveitis and most cases had markedly decreased vision as compared with those treated by us with regular systemic corticosteroids. CONCLUSIONS: Intensive and prolonged systemic treatment with corticosteroids is recommended for the patients with first attack of VKH syndrome, where as regular treatment with chlorambucil is useful for control of chronic and recurrent uveitis seen in VKH syndrome. Traditional Chinese medicine herbs may be helpful in amelioration of uveitis and reduction of side effects of immunosuppressives.