Behçet's syndrome: one year in review 2023.

This critical review of studies on Behçet's syndrome published during 2022 includes studies on epidemiology, patients' perspective, pathogenesis, diagnosis, clinical features and management. Studies on pathogenesis included potential biomarkers mostly related to macrophages, neutrophil and cytokine balance, new GWAS and polymorphism studies, and studies on miRNAs and long non-coding RNAs. Clinical studies showed that application of pneumococcal vaccine to the prick site increased the sensitivity and specificity of the pathergy test and the prevalence of AA amyloidosis had decreased over the years. Studies on management indicated that more data are needed to understand the effect of apremilast on BS manifestations other than oral ulcers, and new BS manifestations may develop during treatment with infliximab. Other biologics and Jak inhibitors might be an option for patients who are refractory to TNF-α inhibitors. Moreover, endovascular repair of arterial aneurysms might be an alternative to open surgery.

Case-control study of corneal topography and specular microscopy parameters in JIA patients with and without ocular involvement.

PURPOSE: To assess corneal topography and specular microscopy values in juvenile idiopathic arthritis-related uveitis (JIA-U). METHODS: This case-control study included 30 eyes from JIA-U patients, 20 eyes from JIA patients, and 50 eyes from age- and gender-matched healthy subjects. Patients with a history of ocular diseases or intraocular surgery were excluded. Corneal topography maps (Pentacam HR) and specular microscopy images (CellChek SL) were obtained. The measurements of the groups were compared. RESULTS: Keratometric astigmatism was higher in the JIA-U group than in the control group (p = 0.040). Patients with astigmatism greater than 1.50D were more common in the JIA-U group than in the control group (p = 0.026). The JIA-U group had higher anterior and posterior elevation values than the control group (p = 0.006, p = 0.025). The density of endothelial cells, coefficient of variation, and hexagonality did not change across groups (p = 0.465, p = 0.096, p = 0.869). The total number of exacerbations and the duration of anterior chamber inflammation were both positively correlated with posterior elevation (r = 0.600, p 0.001; r = 0.583, p 0.001). The age of diagnosis was found to be negatively correlated with anterior elevation (r = -0.412, p = 0.021). CONCLUSION: Corneal astigmatism, as well as anterior and posterior elevation values, were all higher in JIA-U patients. Endothelial cell density and morphology, on the other hand, did not differ significantly between groups. Chronic inflammation's impact on stromal remodelling could explain these corneal alterations. The positive correlation between posterior elevation and the number of flares and duration of inflammation represents the importance of early diagnosis and effective treatment.

Bilateral Cystoid Macular Edema after COVID-19: 1 Year Follow Up.

PURPOSE: The aim is to report a case of bilateral macular edema after COVID-19 pneumonia. CASE REPORT: A 66-year-old male patient with history of COVID-19 pneumonia presented to us with decreased vision. Examination showed bilateral cystoid macular edema (CME), which was confirmed on optical coherence tomography (OCT). There were no findings in the fundus examination. He had no systemic disease, drug or surgery history, or any factors that could explain the clinic presentation. Work-up for uveitis was unremarkable. After topical therapy with brinzolamide 1% and nepafenac 0.1%, macular edema regressed in a month. CONCLUSION: This is an unusual case of CME in previous COVID-19 infection. This presentation may be a parainfectious or a post-viral manifestation of COVID-19.

Behçet's disease risk-variant HLA-B51/ERAP1-Hap10 alters human CD8 T cell immunity.

OBJECTIVES: The endoplasmic reticulum aminopeptidase (ERAP1) haplotype Hap10 encodes for a variant allotype of the endoplasmic reticulum (ER)-resident peptide-trimming aminopeptidase ERAP1 with low enzymatic activity. This haplotype recessively confers the highest risk for Behçet's diseases (BD) currently known, but only in carriers of HLA-B*51, the classical risk factor for the disease. The mechanistic implications and biological consequences of this epistatic relationship are unknown. Here, we aimed to determine its biological relevance and functional impact. METHODS: We genotyped and immune phenotyped a cohort of 26 untreated Turkish BD subjects and 22 healthy donors, generated CRISPR-Cas9 ERAP1 KOs from HLA-B*51 + LCL, analysed the HLA class I-bound peptidome for peptide length differences and assessed immunogenicity of genome-edited cells in CD8 T cell co-culture systems. RESULTS: Allele frequencies of ERAP1-Hap10 were similar to previous studies. There were frequency shifts between antigen-experienced and naïve CD8 T cell populations of carriers and non-carriers of ERAP1-Hap10 in an HLA-B*51 background. ERAP1 KO cells showed peptidomes with longer peptides above 9mer and significant differences in their ability to stimulate alloreactive CD8 T cells compared with wild-type control cells. CONCLUSIONS: We demonstrate that hypoactive ERAP1 changes immunogenicity to CD8 T cells, mediated by an HLA class I peptidome with undertrimmed peptides. Naïve/effector CD8 T cell shifts in affected carriers provide evidence of the biological relevance of ERAP1-Hap10/HLA-B*51 at the cellular level and point to an HLA-B51-restricted process. Our findings suggest that variant ERAP1-Hap10 partakes in BD pathogenesis by generating HLA-B51-restricted peptides, causing a change in immunodominance of the ensuing CD8 T cell response.

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet's syndrome.

There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

Episcleral Iodine-125 radioactive plaque brachytherapy as a salvage treatment for retinoblastoma in the era of intraarterial chemotherapy.

BACKGROUND: Retinoblastoma shows high rates of recurrence after initial chemotherapy (systemic or intraarterial). Our aim was to evaluate the effectiveness of iodine-125 radioactive plaque brachytherapy as a salvage treatment with globe-preserving attributes after initial chemotherapy in patients with intraocular retinoblastoma. METHODS: The effect of brachytherapy was investigated retrospectively in 17 eyes of 17 patients who were followed up due to retinoblastoma between May 2012 and June 2018 and who received iodine-125 radioactive plaque brachytherapy as a salvage treatment after systemic or intra-arterial chemotherapy. The regression, ocular toxicity, and enucleation rates were evaluated at the end of the follow-up period. RESULTS: The tumor locations were post equator, macular, anterior to the equator, and peripapillary in 5, 3, 7, and 2 patients, respectively. Regression was initially and rapidly observed in 17 of the 17 eyes that underwent brachytherapy. Enucleation was performed in 5 (29.42%) of these patients due to recurrence with diffuse tumor involvement, and 4 of the tumors were located anterior to the equator. In 12 (70.58%) patients, the eyes were protected from enucleation following local brachytherapy. CONCLUSIONS: Radioactive plaque brachytherapy can be applied as an effective salvage therapy with successful results in retinoblastoma patients who have received initial systemic or intra-arterial chemotherapy. Post equator-located solitary tumors have the highest success rate.

Comparison of iodine-125 plaque brachytherapy and gamma knife stereotactic radiosurgery treatment outcomes for uveal melanoma patients.

PURPOSE: To compare the efficacies of iodine-125 brachytherapy (IBT) and gamma knife stereotactic radiosurgery (GKRS) in the treatment of posterior uveal melanoma. METHODS: The demographic data and tumor characteristics at diagnosis of 201 patients treated with IBT and 52 patients treated with GKRS were recorded. The two treatments were then compared in terms of complications, local control, eye retention, metastasis, and overall survival rate. RESULTS: The median follow-up time was 56 months for the GKRS group and 45 months for the IBT group (p = 0.167). There were no significant differences in demographic data or tumor characteristics between the groups at diagnosis. Radiation retinopathy, radiation optic neuropathy, and neovascular glaucoma occurred at similar rates in both groups. However, radiation maculopathy and cataracts occurred more frequently in the GKRS group. The number of cases that have developed vision loss (worsening of best-corrected visual acuity on three or more lines on the Snellen chart) was significantly higher in the GKRS group (60%) compared to the IBT group (44%) (p = 0.048). Local control, metastasis, and 5-year overall survival rates were statistically similar in both groups. CONCLUSIONS: GKRS can be preferred as an eye-sparing treatment option for posterior uveal melanoma in cases where brachytherapy cannot be used.

One year in review 2021: Behçet's syndrome.

This review aims to provide a critical digest of the recent studies that enhance our understanding of Behçet's syndrome by evaluating time trends, differences in disease course between men and women, and between patients with an early and late disease onset, progress in disease assessment, novel findings on immunopathogenesis and genetics, clinical features and differential diagnosis of eye, vascular, nervous system and gastrointestinal system involvement, and new data on treatment modalities including TNF-alpha, IL-17 and IL-6 inhibitors, tofacitinib, and apremilast, as well as surgical interventions.

Investigation of clinical profile of Behçet's syndrome-related versus idiopathic branch retinal vein occlusion.

PURPOSE: To compare the long-term results of the patients with branch retinal vein occlusion (BRVO) secondary to Behçet's syndrome (BS) with the patients with unknown etiology. METHODS: Medical records and optical coherence tomography (OCT) imaging results of the patients with BRVO secondary to BS and with unknown etiology were reviewed retrospectively between 2016 and 2018 at a single center. The anatomical location of the BRVO, involvement of the macula, application of laser photocoagulation, and intravitreal injection were evaluated. RESULTS: Twenty-eight eyes of 23 patients with BRVO secondary to BS as the study group and 22 eyes of 19 idiopathic BRVO patients as the control group were included in the study. The mean duration of follow-up after the development of BRVO was 74.6 ± 57.4 months in the study group and 63.6 ± 59 months in the control group. The rate of bilaterality, macular involvement, and application of laser photocoagulation was not statistically significantly different between the groups. However, the frequency of injection requirement was significantly lower in the patients with BRVO secondary to BS in comparison to the control group (P= 0.009). CONCLUSION: Although the treatment of BRVO is laser photocoagulation and intravitreal injection of anti-VEGF agents or dexamethasone implant, the patients with BS might respond very well to systemic immunomodulatory agents in case of BRVO. Thus, rearrangement of the immunomodulatory treatment before starting intravitreal injections should be considered in the patients with BRVO secondary to BS.

Ocular Inflammatory Disorders in Autoimmune Lymphoproliferative Syndrome (ALPS).

PURPOSE: To describe inflammatory ocular findings in patients with autoimmune lymphoproliferative syndrome (ALPS). METHODS: A retrospective review of medical records for ALPS patients seen at the National Eye Institute between 2003 and 2013. RESULTS: A total of 29 ALPS patients previously referred for ocular or visual symptoms or with a history of prolonged corticosteroid use, were identified. Mean age was 20 years (range: 4-66 years). The majority were male (n = 21, 72.4%) and Caucasian (n = 24, 82.8%). Ten (34.5%) had abnormal ocular findings, the most common of which was an ocular inflammatory disorder (n = 4, 13.8%). Uveitis was seen in two patients with ALPS-FAS and one with ALPS-U, all of whom required long-term systemic immunosuppression. One patient with ALPS-FAS had a history of optic neuritis. CONCLUSIONS: ALPS can have intraocular inflammatory manifestations that require routine follow-up to ensure appropriate and timely treatment of intraocular disease. Long-term immunosuppression may be needed for patients with ALPS-associated uveitis.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Histologic Findings of Corneal Buttons in Decompensated Corneas With Toxic Anterior Segment Syndrome After Cataract Surgery.

PURPOSE: To report the histologic findings of penetrating keratoplasty buttons in decompensated corneas with toxic anterior segment syndrome (TASS) after a cataract surgery is performed. METHODS: We evaluated the histologic findings of 16 corneal buttons of 16 patients who exhibited decompensation findings because of TASS by means of light microscopy. The patients were classified into 3 groups: The first group consisted of 5 corneal buttons with mild symptoms in which the central corneal thicknesses (CCTs) were ≤650 µm, and the visual acuities (VAs) were ≥0.1. The second group consisted of 7 corneal buttons that exhibited moderate symptoms in which the CCTs were between 650 and 750 µm and the VAs were between 0.1 and 0.03. The third group consisted of 4 corneal buttons that had severe symptoms in which the CCTs were ≥750 µm and the VAs were ≤0.03. RESULTS: Light microscopy showed endothelial cell loss, vacuolated and thinned epithelial cell layers, disturbed collagen bonds, and Descemet membrane invaginations in patients in group I. Group II corneal buttons exhibited inflammatory cells (lymphocytes) and extended intercellular space between the epithelial cells, wrinkled Bowman membrane separated from the stroma in some local areas, stromal edema, and early vascularization. In group III, endothelial and epithelial cell layer loss, wrinkled Descemet and Bowman membranes, inflammatory cells, and structurally disturbed collagen bonds located beneath the Bowman membrane, and a greater amount of vascularization in the area of inflammation were observed. CONCLUSIONS: The results of the histologic evaluation of the decompensated corneas caused by the TASS are compatible with the clinical severity of the disease. In mild cases, the histologic findings were insignificant; however, when the clinical situation deteriorated, histologic findings became increasingly worse.

Scleral buckling with a non-contact wide-angle viewing system.

PURPOSE: To assess the outcome of scleral buckling surgery using a non-contact wide-angle viewing system for fundus visualization in patients with rhegmatogenous retinal detachment without proliferative vitreoretinopathy. PATIENTS AND METHODS: Sixteen eyes of 16 patients underwent scleral buckling using a non-contact wide-angle viewing system combined with a 25-gauge illumination fibre inserted into the sclera at the pars plana. RESULTS: The mean age of the patients was 53.6 ± 13.7 years and the mean follow-up time was 13.4 ± 2.8 months. Retinal reattachment was achieved in 13 of the 16 eyes (81%). Three eyes underwent vitrectomy with silicone oil injection because of development of proliferative vitreoretinopathy in 2 eyes and scleral perforation due to excessive indentation during cryoretinopexy in 1 eye. Two eyes developed limited subretinal haemorrhage during subretinal fluid drainage. CONCLUSION: Simultaneous use of a non-contact wide-angle viewing system combined with a 25-gauge light fibre illumination for fundus visualization brings the advantages of microsurgery and indirect ophthalmoscopy into scleral buckling surgery.