Functions of mucosal associated invariant T cells in eye diseases.

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.

Clinical Features of Pediatric Uveitis at a Tertiary Referral Center in the Western Region of Japan.

PURPOSE: This study aimed to assess the clinical features of pediatric uveitis at a tertiary referral center in Western Japan. METHODS: One hundred forty eyes of 80 patients aged <20 years at the time of uveitis onset, who visited Kyushu University Hospital between January 2010 and December 2019 were included in this study. Clinical records were retrospectively reviewed. Demographics, clinical findings, treatments, and visual prognoses were compared between the disease groups. RESULTS: Of 80 patients, 32 were males and 48 were females. The average age of onset was 12.5 ± 4.8 (0-19) years. Tubulointerstitial nephritis and uveitis (TINU) and juvenile idiopathic arthritis (JIA) were the most frequent causes, accounting for 11.3% and 10% of cases, respectively, followed by sarcoidosis (5%), Behçet's disease, acute anterior uveitis, Vogt-Koyanagi-Harada disease, and juvenile chronic iridocyclitis (3.8% each). Infectious uveitis accounted for 7.6% of the cases: cytomegalovirus was the most frequent agent. Of these cases, 43.8% were unclassified. Systemic therapies were administered to 87.5% of the patients with JIA, 33.3% of those with TINU, and 28.6% of the other diagnostic groups. In the unclassified group, 80% of the patients were followed up with only topical corticosteroids. LogMAR visual acuity of 0 or less accounted for more than 80% in the final examination. CONCLUSION: TINU and JIA were the most common causes of pediatric uveitis. Although each required systemic therapy, most unclassified cases of pediatric uveitis were managed by topical corticosteroids alone with good visual prognosis. Accurate diagnosis is important for pediatric uveitis management.

Long-term outcomes of infliximab in patients with Behçet's disease-associated uveitis.

OBJECTIVES: To evaluate long-term outcomes of infliximab (IFX) treatment in patients with Behçet's disease (BD)-associated uveitis. PATIENTS AND METHODS: We retrospectively analyzed the cases of patients with BD-associated uveitis treated with IFX for > 5 years. We compared the numbers of ocular inflammatory attacks, ocular disease activities, and visual acuity before and after the initiation of IFX treatment. RESULTS: The 24 patients were 20 men and 4 women. Their mean age at the initiation of IFX treatment was 37.3 ± 9.2 years. The mean term from the initiation of IFX treatment was 10.3 ± 2.4 years. The average number of ocular inflammatory attacks was 5.4 ± 2.1 per 12 months before the IFX treatment and significantly lower at 0.83 ± 0.96 per 12 months after the initiation of IFX treatment (p < 0.05). We used a scoring system for BD-associated uveitis named the Behçet's disease ocular attack score 24 (BOS24) to estimate the changes in ocular disease activities between before and after initiation of IFX treatment. The average score decreased significantly from 7.58 ± 2.77 to 2.55 ± 2.74 after the initiation of IFX treatment (p < 0.05). Even after > 5 years of the treatment, both the number of ocular attacks and the BOS24 score kept decreasing. The visual acuity in 42 of 48 eyes (24 patients) was improved or maintained. CONCLUSIONS: IFX was effective for controlling ocular inflammatory attacks and diminishing ocular disease activities in patients with BD-associated uveitis, and it maintained the patients' visual acuity.

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.

Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which enables these CMV strains to escape HLA-E-restricted CD8+T cell responses. Variations in UL40 sequences have been studied mainly in the peripheral blood of CMV-viremia cases. In this study, we sought to investigate how ocular CMV disease develops from CMV infections. CMV gene sequences were compared between the intraocular fluids and peripheral blood of 77 clinical cases. UL40 signal peptide sequences were more diverse, and multiple sequences were typically present in CMV-viremia blood compared to intraocular fluid. Significantly stronger NK cell suppression was induced by UL40-derived peptides from intraocular HCMV compared to those identified only in peripheral blood. HCMV present in intraocular fluids were limited to those carrying a UL40 peptide sequence corresponding to the leader peptide sequence of the host's HLA class I, while UL40-derived peptides from HCMV found only in the peripheral blood were disparate from any HLA class I allotype. Overall, our analyses of CMV-retinitis inferred that specific HCMV strains with UL40 signal sequences matching the host's HLA signal peptide sequences were those that crossed the blood-ocular barrier to enter the intraocular space. UL40 peptide repertoires were the same in the intraocular fluids of all ocular CMV diseases, regardless of host immune status, implying that virus type is likely to be a common determinant in ocular CMV disease development. We thus propose a mechanism for ocular CMV disease development, in which particular HCMV types in the blood exploit peripheral and central HLA-E-mediated tolerance mechanisms and, thus, escape the antivirus responses of both innate and adaptive immunity.

Panuveitis induced by donor-derived CD8+ T cells after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia.

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X- and Y-chromosome probes revealed complete donor chimerism in CD8+ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8+ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8+ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

The Effects of Speed-Modulated Visual Stimuli Seen through Smart Glasses on Work Efficiency after Viewing.

It is known that subjective time and work efficiency are affected by visual stimuli. However, existing studies only consider the effects of visual information on the user during viewing and ignore the after effects. Using smart glasses lets users see visual information while moving until just before arriving at the office or school. We hypothesize that the user's effects from the visual information they were looking at just before working or studying affects the subsequent work. Through two user studies, we investigated whether information presented on smart glasses affected subsequent work efficiency. In the first experiment, participants were presented with avatars running at two levels of speed, or no avatars, through simulated smart glasses in a virtual environment. They then solved a dot-clicking task on a desktop monitor. In the second experiment, we investigated whether the same effect could be shown while walking in the real environment, with a running and a fast-walking avatar both at the same speed in order to see the difference in the effects of the different movements. In the first experiment, we confirmed that the speed of later work tended to improve when presenting the running human-shaped avatar. From the results of the second experiment, which was conducted in the real environment, we did not confirm that the subsequent work speed varied depending on the type of avatar being displayed. As a reason for the trend of improvement in the task efficiency in the first experiment, observation of fast human motion may have unconsciously accelerated the observers' body movement speed due to the mirror neuron mechanism. As a reason for why the work speed did not improve in the second experiment, the participants may be affected by other pedestrians and running cars. Additionally, it was difficult to see the images on the smart glasses while walking in the real environment.

Increased vitreous levels of B cell activation factor (BAFF) and soluble interleukin-6 receptor in patients with macular edema due to uveitis related to Behçet's disease and sarcoidosis.

PURPOSE: Uveitis accounts for 10-15% of all cases of blindness in the developed world. Uveitic macular edema (UME) is a primary cause of permanent visual impairment in patients with uveitis. Because proinflammatory mediators elicit inflammation and lead to UME, we determined the profiles of proinflammatory mediators associated with complications, such as ME, in the vitreous humor of patients with panuveitis related to Behçet's disease (BD) and sarcoidosis. METHODS: In this retrospective study, we enrolled 21 patients with uveitis, including 6 with BD and 15 with sarcoidosis, and 15 patients with idiopathic epiretinal membrane (iERM) at the Department of Ophthalmology, Kyushu University Hospital, between January 2008 and April 2016. Vitreous concentrations of 32 proinflammatory mediators, including cytokines and soluble receptors of tumor necrosis factor (TNF) and interleukin (IL)-6 families, were assessed using a bead-based multiplex assay and their association with clinical data was examined. RESULTS: The levels of proinflammatory mediators, including a proliferation-inducing ligand (APRIL), B cell activating factor belonging to the TNF family (BAFF), soluble cluster of differentiation 30 (sCD30), soluble TNF receptor-1 (sTNFR1), sTNFR2, TNF-α, IL-6, and soluble IL-6 receptor-α (sIL-6Rα), were significantly higher in patients with uveitis. With regard to clinical parameters in patients with uveitis, vitreous levels of BAFF and sIL-6Rα were prominently elevated in patients with UME compared to in those without UME (P < 0.01, respectively). CONCLUSIONS: Our results suggest that elevated vitreous levels of BAFF and sIL-6Rα are associated with the pathogenesis of UME in patients with panuveitis related to BD and sarcoidosis.

Multicenter, retrospective, observational study for the Treatment Pattern of systemic corticoSTERoids for relapse of non-infectious uveitis accompanying Vogt-Koyanagi-Harada disease or sarcoidosis.

PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.

Corrigendum: Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.

[This corrects the article DOI: 10.3389/fimmu.2022.1008220.].

Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity.

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt-Koyanagi-Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161highTRAV1-2+ mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.

Optical coherence tomography angiography of choroidal neovascularization in immune choroiditis following acute retinal necrosis.

PURPOSE: To report optical coherence tomography angiography (OCTA) findings in a case of immune choroiditis following contralateral acute retinal necrosis (ARN) with choroidal neovascularization (CNV) during anti-vascular endothelial growth factor (VEGF) therapy. CASE REPORT: A 64-year-old woman with immune choroiditis following contralateral ARN and secondary CNV presented with decreased visual acuity. Fundus examination revealed macular and peripheral yellowish lesions in the right eye. Inflammatory cells were observed in the anterior chamber and the vitreous. OCT revealed retinal exudative changes and subretinal lesions suggestive of CNV. OCTA detected an abnormal vascular net in the outer retina as well as choriocapillaris, corresponding to type 2 CNV, that reduced following intravitreous anti-VEGF therapy. Two weeks after treatment, OCTA showed re-dilated choroidal neovasculature at the outer retina despite no exudative recurrence in OCT. Six weeks after treatment, OCT detected exudative changes around the neovascular lesion. CONCLUSION: This case discusses the use of OCTA detection of CNV in a case of immune choroiditis following contralateral ARN. During anti-VEGF therapy for inflammatory CNV-related diseases, OCTA may be useful not only for CNV detection but also for the follow-up of CNV activity.

Surgical Outcomes of Contrast Sensitivity and Visual Acuity in Uveitis-Associated Cataract.

PURPOSE: To evaluate the pre- and post-operative outcomes of phacoemulsification in patients with uveitis-associated cataract in remission, such as conventional visual acuity (VA), photopic and mesopic contrast visual acuity (CVA), and flares in the anterior chamber objectively assessed as intraocular inflammation. PATIENTS AND METHODS: This prospective study included 26 eyes of 19 patients with uveitis and 45 eyes of 26 controls who underwent cataract surgery at the Kyushu University Hospital and Kyushu Medical Center in Fukuoka, Japan, from October 2016 to December 2018. Conventional VA and flare values in the anterior chamber were evaluated preoperatively and 1 and 3 months postoperatively. Photopic and mesopic CVAs were assessed preoperatively and 3 months postoperatively. RESULTS: The best-corrected VA (BCVA) was improved significantly from baseline to 1 and 3 months postoperatively in both groups (P < 0.01 in both groups). The mean preoperative 100% and 10% CVAs under the photopic condition were significantly lower in the uveitis group than in the control group (P < 0.05 for both CVA), whereas the mean preoperative 100% CVA under the mesopic condition was comparable between the two groups. Although the mean preoperative 100% and 10% CVAs improved significantly from baseline under both photopic and mesopic conditions in both groups (P < 0.01 in both groups), the postoperative contrast sensitivities under both photopic and mesopic conditions remained lower in the uveitis group than in the control group (P < 0.01 for both conditions). The postoperative complications included recurrence of active inflammation in five eyes and cystoid macular edema in one eye and were managed by topical steroid therapy alone. CONCLUSION: Cataract surgery for uveitis-associated cataracts during remission is well tolerated. However, the present results suggest that amelioration of hemeralopia and/or nyctalopia is not as good as expected after cataract surgery in patients with uveitis.

Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus.

PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). DESIGN: Retrospective, multicenter case series. METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus. RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU. CONCLUSION: This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.

Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey.

PURPOSE: To investigate the epidemiology of uveitis in Japan and assess its changes over time. STUDY DESIGN: Retrospective multicenter study METHODS: Sixty-six hospitals in Japan with uveitis specialty clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria. RESULTS: In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey; 3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt-Koyanagi-Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet's disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner-Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet's disease were similar; however, the rate of herpes iritis increased (4.2-6.5%) when compared with the 2009 survey. CONCLUSIONS: Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.

Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma.

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Vitreous concentrations of regulatory cytokines were assessed using a cytometric beads assay and association with clinical data was examined. IL-35 and soluble IL-2 receptor α levels were significantly higher in patients with VRL and NIU than those in the control group. The 5-year overall survival (OS) rates for the group with high intravitreal IL-35 was significantly poorer than those for the group with low intravitreal IL-35, who were diagnosed with VRL at the onset (P = 0.024, log-rank test). The 5-year OS rates with intravitreal IL-35 levels above and below the median were 40.0% and 83.3%, respectively. Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset.

RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization.

Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1K45A/K45A mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.

The effectiveness of adalimumab treatment for non-infectious uveitis.

Uveitis, which is a major cause of blindness worldwide, is defined as intraocular inflammation that affects the iris, ciliary body, vitreous, retina and choroid. Tumor necrosis factor-alpha (TNF-α) is a key cytokine involved in the pathogenesis of many inflammatory diseases including uveitis. Corticosteroids and immunosuppressive agents are the conventional therapy to treat non-infectious uveitis. In cases that are resistant to these therapies, anti-TNF agents are added. An anti-TNF-α agent, adalimumab, was recently approved for the treatment of refractory non-infectious uveitis. In this review, we provide an introduction to uveitis and summarize the effectiveness and safety of adalimumab in the treatment of non-infectious uveitis.

Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma.

PURPOSE: To determine the factors that may affect the accuracy of vitrectomy cell block technique in detecting atypical lymphoid cells in patients with vitreoretinal lymphoma (VRL). METHODS: We retrospectively reviewed 43 eyes in 39 patients who underwent vitrectomy for definitive histological diagnosis of VRL with vitrectomy cell block technique and/or smear preparation at Kyushu University Hospital from January 2001 to March 2016. The association of detection of atypical lymphoid cells using vitrectomy cell block technique with the following factors was assessed using logistic regression analysis: age at diagnosis, sex, presence or absence of concurrent cataract surgery with vitrectomy, clinical grading of vitreous haze, presence or absence of subretinal tumor infiltration, interval between initial symptoms and vitrectomy, and presence or absence of systemic corticosteroid therapy before vitrectomy. RESULTS: Atypical lymphoid cells were more significantly detected using vitrectomy cell block technique compared to that using smear preparation (p = 0.018). After adjusting for age and sex, concurrent cataract surgery (odds ratio [OR], 10.41; 95% confidence interval [CI], 1.42-76.41) and subretinal tumor infiltration (OR, 5.06; 95% CI, 1.06-24.32) were significantly associated with failure of histological analysis with vitrectomy cell blocks. In multivariable logistic regression analysis, similar results were obtained, although subretinal tumor infiltration was only marginally associated with the detective capability of the technique. CONCLUSION: Vitrectomy cell block technique significantly improved the definitive diagnosis of VRL. Concurrent cataract surgery with vitrectomy and subretinal tumor infiltration were risk factors for failure in vitrectomy cell blocks.

Preoperative estimation of distance between retinal break and limbus with wide-field fundus imaging: Potential clinical utility for conventional scleral buckling.

OBJECTIVE: Accurate scleral marking of retinal breaks is essential for successful scleral buckling. This study aimed to investigate the use of wide-field fundus images obtained with an Optos for preoperative estimation of the distance from the limbus to the retinal breaks. METHODS AND ANALYSIS: This is a retrospective review of 29 eyes from 26 patients with rhegmatogenous retinal detachment who received scleral buckling with anatomically successful repair. They underwent wide-field fundus photography with Optos California. In the pre- and postoperative fundus images, we measured distances from the macula to the retinal tears (TM), to the center of the vortex veins (VM), to the optic disc (DM), and to the posterior edge of the scleral buckle (BM). RESULTS: (BM-VM) / DM was significantly correlated with the distance from the limbus to the posterior edge of the scleral buckle that had been determined intraoperatively. (r = 0.705; p<0.001) We applied a regression line derived from this correlation with the value of (TM -VM) / DM in order to calculate estimated distances between retinal breaks and the limbus. The calculated distances were all within the range of distances from the limbus to the anterior and posterior edges of the scleral buckles. CONCLUSION: Preoperative analysis of Optos images may be useful for estimating the distance from the limbus to retinal breaks, which might aid scleral marking during scleral buckling surgery.