Efficacy and safety of tumor necrosis factor inhibitors for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies. RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%. CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.

Efficacy and safety of abatacept for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.

Clinical features and visual outcomes of ocular sarcoidosis at a tertiary referral center in Tokyo.

BACKGROUND: To analyze clinical features, treatment, complications, and visual outcomes of ocular sarcoidosis at a tertiary center in Tokyo. METHODS: Clinical records of 53 patients with ocular sarcoidosis ("definite" or "presumed") presenting between 2013 and 2018 to the Kyorin Eye Center were retrospectively reviewed. Diagnosis was based on the revised criteria of the International Workshop on Ocular Sarcoidosis. RESULTS: Definite (biopsy-proven) disease was present in 87% of patients and presumed disease in 13%. The mean age at presentation was 58 years (13-81 years) and 68% were women. The mean follow-up was 34 months (6-70 months). Forty-five patients (85%) had panuveitis, and the most common ocular clinical sign suggestive of ocular sarcoidosis was bilaterality (92%). Ocular complications were observed in 93 eyes (85%), most commonly cataract (73%), epiretinal membrane (24%), macular edema (24%) and glaucoma (19%). Thirty-one eyes (30%) underwent cataract surgery and 12 eyes (12%) underwent pars plana vitrectomy. Ten patients (19%) received systemic corticosteroid therapy and 33 eyes (32%) received periocular corticosteroid injections. The best-corrected visual acuity was 1.0 or better in 51% of eyes at presentation, 57% at 6 months, 50% at 12 months, and 58% at 36 months. CONCLUSIONS: The majority of ocular sarcoidosis patients were women, had bilateral disease and panuveitis involvement. Most eyes maintained good visual acuity, although surgical interventions for cataract and epiretinal membrane were common.

Genetic Ablation of Nrf2 Exacerbates Neuroinflammation in Ocular Autoimmunity.

Experimental autoimmune uveoretinitis (EAU) is an animal model of non-infectious uveitis and is developed by immunization with retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). Nuclear factor erythroid 2- (NF-E2-) related factor 2 (Nrf2) is responsible for regulating antioxidant and inflammatory responses. In this study, we investigated the role of Nrf2 on the development of EAU. Clinical and pathological examination demonstrated that retinal inflammation was exacerbated in Nrf2 knockout (Nrf2 KO) mice compared to wild type (WT) mice, and the expression of inflammatory cytokines (IFN-γ, IL-6, and IL-17) in the retina was significantly elevated in Nrf2 KO mice. GFAP positive cells (astrocytes) and Iba-1 positive cells (microglia cells) in the retina were more numerous in Nrf2 KO mice compared to WT mice. Furthermore, we examined the suppressive effect of the Nrf2 activator CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline) on the development of EAU. The treatment with CDDO-Im significantly reduced the clinical and pathological score of EAU compared to those of vehicle-treated mice. These findings suggest that Nrf2 plays a regulatory role in the pathogenesis of autoimmune uveoretinitis and the activation of the Nrf2 system may have therapeutic potential for protecting vision from autoimmune neuroinflammation.

Circulating Vitreous microRNA as Possible Biomarker in High Myopic Eyes with Macular Hole.

High myopia is a major cause of irreversible visual impairment globally. In the present study, we investigated the microRNA (miRNA) profile in the vitreous of macular hole (MH) and high myopic MH. We performed miRNA analysis using TaqMan® Low Density Arrays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate the circulating vitreous miRNA profile from patients with MH (axial length < 26.5 mm, n = 11) and high myopic MH (axial length ≥ 26.5 mm, n = 11) who underwent pars plana vitrectomy. The vitreous inflammatory cytokine signature was examined in high myopic MH eyes using a multiplex assay. A miRNA-Array analysis revealed that let-7c was significantly up-regulated and miR-200a was significantly down-regulated in high myopic MH eyes compared to those in MH eyes. The bioinformatics analysis for up-regulated miRNA targeted gene identified 23 pathways including mitogen-activated protein kinase (MAPK) and several inflammatory signaling pathways, whereas the bioinformatics analysis for down-regulated miRNA targeted genes showed 32 enriched pathways including phosphoinositide 3-kinase/protein kinase B (PI3K/AKT). The levels of inflammatory cytokines including IP-10, IFN-γ, and MCP-1 were significantly higher in the vitreous of high myopic MH eyes. These results suggest that specific miRNAs expressed in the vitreous may be associated with the pathological condition of high myopic MH and the above mentioned miRNAs may contribute to the development of inflammatory status in the vitreous of high myopic eyes.

Comparative Analysis of Serum microRNA in Diagnosed Ocular Sarcoidosis versus Idiopathic Uveitis with Ocular Manifestations of Sarcoidosis.

"Idiopathic" is the most common category of uveitis, representing cases in which a specific diagnosis has not been established despite work-up. Sarcoidosis is a systemic granulomatous disorder affecting multiple organs including the lungs, skin, kidneys, and eyes. We used microRNA (miRNA) microarrays to investigate serum miRNA profiles of patients with ocular sarcoidosis as diagnosed by specific criteria (diagnosed ocular sarcoidosis), and patients with idiopathic uveitis characterized by ocular manifestations of sarcoidosis (suspected ocular sarcoidosis). Principal component analysis (PCA) and hierarchical clustering showed that serum miRNA profiles of diagnosed ocular sarcoidosis and suspected ocular sarcoidosis were both clearly distinguishable from healthy controls. Furthermore, comparative analysis of the miRNA profiles showed highly similar patterns between diagnosed ocular sarcoidosis and suspected ocular sarcoidosis. Pathway analysis revealed common pathways were involved in the two groups, including those of WNT signaling and TGF-beta signaling. Our study demonstrated a high overlap of differentially expressed serum miRNAs in patients with diagnosed ocular sarcoidosis and suspected ocular sarcoidosis, suggesting that these groups share a similar underlying pathology and may represent possible variants of the disease. Characterization of serum miRNA profiles may provide an opportunity for earlier diagnosis and treatment, and may inform more accurate clinical prognosis in patients with an ocular sarcoidosis phenotype.

Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease.

Behçet's disease is a systemic inflammatory disorder with recurrent episodes of oral ulceration, skin lesions, genital ulceration, and intraocular inflammation (uveitis). The intraocular inflammation is strictly associated with Th effector cells. IL-22 is a member of the IL-10 cytokine family that is involved in inflammatory processes. Recently, Th22 cells were identified as a Th cell population that produces IL-22 and TNF-α and are distinct from Th1, Th2, and Th17 cells. In this study, we established Th22-type T cell clones from ocular samples taken from Behçet's disease patients with active uveitis. These clones produced large amounts of IL-22 and TNF-α but not the Th1 cytokine IFN-γ and the Th17 cytokine IL-17. CD4(+) T cells from the peripheral blood of Behçet's disease patients differentiated into Th22 cells in the presence of IL-6 and TNF-α in vitro. The polarized Th22 cell lines produced large amounts of IL-22, and the polarized Th1 and Th17 cells also produced IL-22. In the presence of anti-TNF-α- and anti-IL-6-blocking Abs, Behçet's disease Th22-type T cells failed to produce IL-22. In addition, infliximab-pretreated Th22 cells and Th22-type ocular T cells produced less IL-22 and TNF-α. Moreover, IL-22-producing T cells were isolated from mice with experimental autoimmune uveitis, an animal model of Behçet's disease, and the intraocular T cells from uveitis models produced large amounts of IL-22 in the presence of retinal Ags. Our results suggest that inflammatory cytokines IL-22 and TNF-α may play a key role in the ocular immune response in Behçet's disease.

Comparisons of microRNA expression profiles in vitreous humor between eyes with macular hole and eyes with proliferative diabetic retinopathy.

PURPOSE: MicroRNAs (miRNAs) are small noncoding RNAs which regulate the activities of target mRNAs. We compared the expression profiles of the miRNAs in the vitreous of eyes with macular hole (MH) to that in eyes with proliferative diabetic retinopathy (PDR). METHODS: Vitreous and whole blood samples were collected from four patients with MH and from four patients with PDR. We assayed for 168 miRNAs in the vitreous and serum samples by the microRNA PCR Panel method. RESULTS: The mean number of miRNAs expressed in the vitreous was 63 (55-69) in eyes with MH and 86 (65-117) in eyes with PDR. The mean number of miRNAs expressed in the serum was 162 (159-167) in the MH patients and 142 (115-160) in the PDR patients. Twenty-six miRNAs were expressed in the vitreous of both MH and PDR eyes. Although there was no significant difference in the levels of 20 of the 26 (73 %) miRNAs expressed in both MH and PDR eyes, six of 26 miRNAs (24 %) (hsa-miR-15a, hsa-miR320a, hsa-miR-320b, hsa-miR-93, hsa-miR-29a, and hsa-miR-423-5p) were expressed significantly more highly in PDR eyes. In addition, the mean fold changes of three miRNAs, hsa-miR-23a, hsa-miR-320a, and hsa-miR-320b, in the vitreous to serum were significantly higher in the PDR group than in the MH group. CONCLUSIONS: The expression of several miRNAs related to angiogenesis and fibrosis was expressed significantly higher in the vitreous of eyes with PDR. Further studies are needed to understand the role played by the miRNAs in the biological function of the eye.

Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1ß in human corneal fibroblasts.

PURPOSE: Dehydroxymethylepoxyquinomicin (DHMEQ) is derived from the antibiotic, epoxyquinomicin C, and is a novel low molecular weight nuclear factor-κB (NF-κB) inhibitor. We investigated the effects of DHMEQ on the expression of chemokines and the intercellular adhesion molecule (ICAM)-1 induced by proinflammatory cytokines in cultures of the human corneal fibroblasts (HCFs). METHODS: The cytotoxicity of DHMEQ on cultured HCFs was evaluated by cell proliferation assays. Cultures were exposed to interleukin (IL)-1ß, and the production of IL-8 and monocyte chemoattractant protein (MCP)-1 was assessed by enzyme-linked immunosorbent assay. The degree of expression of ICAM-1 was measured by flow cytometry. The translocation of NF-κB p65 into the nucleus of HCFs was assessed by immunocytochemistry. RESULTS: DHMEQ was not toxic to cultured HCFs at doses up to 10 µg/ml. DHMEQ significantly suppressed the production of both IL-8 and MCP-1 in IL-1ß-stimulated HCFs. In addition, DHMEQ down-regulated ICAM-1 expression in IL-1ß-stimulated HCFs in a dose-dependent manner. DHMEQ inhibited the IL-1ß-induced nuclear accumulation of p65, a component of NF-κB, in HCFs. CONCLUSIONS: The suppression of inflammatory chemokines IL-8 and MCP-1 and inhibition of the expression of ICAM-1 in cultured HCFs by DHMEQ indicates that DHMEQ may have a therapeutic potential for treating ICAM-1 and chemokine-mediated corneal inflammatory disorders.

Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis.

BACKGROUND: To determine whether all-trans retinoic acid or a synthetic retinoic acid receptor-α/ß-specific agonist, Am80, can reduce the degree of experimental autoimmune optic neuritis in mice with experimental autoimmune encephalomyelitis. METHODS: Optic neuritis was induced in C57BL/6 mice by immunizing them with myelin oligodendrocyte glycoprotein35-55 . All-trans retinoic acid (350 µg/mouse/time point) or Am80 (5 mg/kg/time point) was administered every other day from day 0 to day 20. The degree of experimental autoimmune encephalomyelitis was scored and histopathological analysis of the optic neuritis was performed on day 22 after the immunization. In vivo-primed draining lymph node cells obtained from vehicle-treated or all-trans retinoic acid-treated mice were stimulated with myelin oligodendrocyte glycoprotein35-55 , and the culture supernatant was collected for assays of interferon-γ and interleukin-17. RESULTS: All-trans retinoic acid treatment significantly reduced the clinical score of experimental autoimmune encephalomyelitis and the severity of the optic neuritis by histopathological analysis. The production of interferon-γ and interleukin-17 was significantly reduced in all-trans retinoic acid-treated mice compared with vehicle-treated mice. Am80 treatment also significantly decreased the severity of the optic neuritis in mice with experimental autoimmune encephalomyelitis. CONCLUSIONS: These findings demonstrate that all-trans retinoic acid and Am80 treatment were able to reduce the severity of optic neuritis in mice with experimental autoimmune encephalomyelitis. Activation of retinoic acid receptor-α/ß may be a molecular target for the treatment of autoimmune optic neuritis induced by Th1 or Th17-dominated immune responses.

Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet's disease: a multicenter study.

PURPOSE: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behçet's disease (BD). DESIGN: Retrospective multicenter study using a questionnaire. PARTICIPANTS: A total of 164 consecutive patients with BD treated with infliximab for more than 1 year were studied. The mean age at initiation of infliximab treatment was 42.6±11.7 years, and the mean treatment duration was 32.9±14.4 months. METHODS: Data before and at the last visit during infliximab treatment were analyzed in 4 groups divided by duration of treatment: group A (n = 43, 12-<24 months), group B (n = 62, 24-<36 months), group C (n = 42, 36-<48 months), and group D (n = 17, ≥48 months). MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), relapse of ocular inflammation, numbers of ocular inflammatory attacks per year, and adverse effects of infliximab therapy. RESULTS: The frequency of ocular attacks decreased in all groups (from 5.3±3.0 to 1.0±0.3 in group A, 4.8±4.6 to 1.4±0.3 in group B, 4.1±2.9 to 0.9±0.3 in group C, and 9.5±5.8 to 1.6±0.5 in group D; all P < 0.05). The BCVA was improved in approximately 55% of the eyes after treatment. Mean BCVA converted to logarithm of the minimum angle of resolution was improved after treatment with infliximab in groups A to C (from 0.79±1.04 to 0.59±0.94 in group A, 0.59±1.07 to 0.41±1.04 in group B, and 1.15±1.77 to 0.92±1.73 in group C; all P < 0.05) but not in group D. Uveitis relapsed in 59.1% of all patients after infliximab treatment, and no difference in duration until relapse was observed between individual groups. Approximately 80% of relapses occurred within 1 year after the initiation of infliximab treatment in all groups, 90% of which were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 65 cases or 35% of all subjects. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy. CONCLUSIONS: Infliximab reduced the frequency of ocular attacks and improved visual acuity in patients with BD-related uveitis and was generally well tolerated with few serious adverse events.

A COVID-19 Risk Reduction Strategy for the Treatment of Acute Vogt-Koyanagi-Harada Disease Utilizing the Antiviral Potential of Cyclosporine.

PURPOSE: To report on the successful treatment of patients with acute Vogt-Koyanagi-Harada (VKH) disease utilizing the antiviral potential of cyclosporine during the COVID-19 pandemic. STUDY DESIGN: Case series. METHODS: Clinical records were retrospectively reviewed of 4 patients presenting with new-onset acute VKH disease who elected to receive initial treatment consisting of bilateral sub-Tenon injection of triamcinolone acetonide combined with immediately starting oral cyclosporine without the use of systemic corticosteroids. RESULTS: The mean follow-up was 17.0 months. Choroidal thickness decreased to normal with recovery of bilateral best-corrected visual acuity (BCVA) of 1.2 in 3 patients. One elderly patient had decreased BCVA (OD 0.5, OS 0.8) due to cataract progression and mild epiretinal membrane. No recurrences of intraocular were observed in any patients. Mild renal dysfunction developed in 2 elderly patients, but importantly no patients developed COVID-19 disease. CONCLUSIONS: Oral cyclosporine as the initial systemic treatment of acute VKH disease, in combination with sub-Tenon injection of triamcinolone acetonide, lead to favorable clinical outcomes. Due to the known antiviral properties of cyclosporine, we suggest that this may represent a good treatment strategy for patients during the COVID-19 pandemic.

A multicenter study of ocular inflammation after COVID-19 vaccination.

PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Design: Retrospective longitudinal cohort study. Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study. Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). Main outcome measures: 10-year IFX continuation rate and change in LogMAR VA. Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

Retinoic acid from retinal pigment epithelium induces T regulatory cells.

Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor ß (TGFß) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGFß. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGFß. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGFß. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGFß promotion, which can then participate in the establishment of immune tolerance in the eye.

Enhanced depth imaging optical coherence tomography of the choroid in Vogt-Koyanagi-Harada disease.

PURPOSE: Optical coherence tomography (OCT) using enhanced depth imaging (EDI) allows evaluation of choroidal thickness. Our objective was to analyze subfoveal choroidal thickness by EDI-OCT before and after the initiation of high-dose corticosteroid treatment in 8 patients (16 eyes) with new-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective review of clinical records. RESULTS: The outer border of the choroid was not evident by EDI-OCT in any patients at presentation. Subfoveal choroidal thickness was measurable by 1 week after the initiation of treatment (mean, 578 µm) and decreased thereafter (mean at 1 month, 397 µm; 3 months, 392 µm; 6 months, 384 µm; 12 months, 332 µm). Rebound of choroidal thickening was observed in three patients (five eyes) during corticosteroid tapering in the absence of other evidence of increased inflammation. Peripapillary atrophy was present at 12 months in 6 of 6 eyes that had a choroidal thickness >550 µm at 1 week after initiating treatment, in contrast to none of the 8 eyes with a choroidal thickness ≤550 µm (P = 0.0003). CONCLUSION: Enhanced depth imaging-optical coherence tomography revealed decreasing choroidal thickness with high-dose corticosteroid treatment in our patients. Choroidal thickness as measured by EDI-OCT may serve as a marker for degree of choroidal inflammation in acute VKH disease.

Automated Quantitative Analysis of Anterior Segment Inflammation Using Swept-Source Anterior Segment Optical Coherence Tomography: A Pilot Study.

Background: The aim of this study is to develop an automated evaluation of anterior chamber (AC) cells in uveitis using anterior segment (AS) optical coherence tomography (OCT) images. Methods: We analyzed AS swept-source (SS)-OCT (CASIA 2) images of 31 patients (51 eyes) with uveitis using image analysis software (Python). An automated algorithm was developed to detect cellular spots corresponding to hyper-reflective spots in the AC, and the correlation with Standardization of Uveitis Nomenclature (SUN) grading AC cells score was evaluated. The approximated AC grading value was calculated based on the logarithmic approximation curve between the number of cellular spots and the SUN grading score. Results: Among 51 eyes, cellular spots were automatically segmented in 48 eyes, whereas three eyes (all SUN grading AC cells score: 4+) with severe fibrin formation in the AC were removed by the automated algorithm. The AC cellular spots increased with an increasing SUN grading score (p < 0.001). The 48 eyes were split into training data (26 eyes) and test data (22 eyes). There was a significant correlation between the SUN grading score and the number of cellular spots in 26 eyes (rho: 0.843, p < 0.001). There was a significant correlation between the SUN grading score and the approximated grading value of 22 eyes based on the logarithmic approximation curve (rho: 0.774, p < 0.001). Leave-one-out cross-validation analysis demonstrated a significant correlation between the SUN grading score and the approximated grading value of 48 eyes (rho: 0.748, p < 0.001). Conclusions: This automated anterior AC cell analysis using AS SS-OCT showed a significant correlation with clinical SUN grading scores and provided SUN AC grading values as a continuous variable. Our findings suggest that automated grading of AC cells could improve the accuracy of a quantitative assessment of AC inflammation using AS-OCT images and allow the objective and rapid evaluation of anterior segment inflammation in uveitis. Further investigations on a large scale are required to validate this quantitative measurement of anterior segment inflammation in uveitic eyes.