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Tetsuya Hasegawa, Misaki Hirato, Chieko Kobashi, Aya Yamaguchi, Rina Takagi, Yoshiaki Tanaka, Toshikatsu Kaburaki, Akihiro Kakehashi Department of Ophthalmology, Saitama Medical Center Jichi Medical University, Saitama-shi, Saitama-ken, JapanCorrespondence: Akihiro KakehashiDepartment of Ophthalmology, Saitama Medical Center Jichi Medical University, Saitama-shi, Saitama-ken, JapanTel +81 48 647 2111Fax +81 48 648 5166Email kakeaki@omiya.jichi.ac.jpPurpose: To evaluate the foveal avascular zone (FAZ) and retinal structure in familial exudative vitreoretinopathy (FEVR).Patients and Methods: Eighteen eyes with stage 1 or 2 FEVR and 20 control eyes were evaluated. The central retinal thickness (CRT), foveal inner retinal thickness (IRT), surface retinal vessel density (SRVD), and deep retinal vessel density (DRVD) were measured using optical coherence tomography. The FAZ area was calculated using ImageJ software. The equivalent spherical value (SE) and axial length (AL) were measured.Results: The CRT (232.5± 3.086 vs 211± 12.6325 μm; p=0.003) and foveal IRT (15.83± 13.95 vs 0.9± 4.02 μm; p=0.002) were thicker in the FEVR group than in the control group. The surface FAZ area (0.265± 0.08 vs 0.364± 0.09 mm2; p=0.004) and the deep FAZ area (0.364± 0.1 vs 0.484± 0.11 mm2; p=0.03) were smaller in the FEVR group than in the control group. The SRVD values did not differ among the sectors, but the DRVD was higher in the FEVR group except for the inferior sector (superior, p=0.027; inferior, p=0.88; temporal, p=0.035; nasal, p=0.027). The SE and AL did not differ between the two groups. There were no correlations between the surface and deep layer FAZ area and age, CRT, SE, and AL. The surface, deep FAZ area, and foveal IRT were correlated negatively (surface, r = − 0.47, p=0.033; deep layer FAZ area, r = − 0.46, p=0.037).Conclusion: Eyes with FEVR have a smaller FAZ because the vascular structure in the inner retina remained in the fovea.Keywords: familial exudative vitreoretinopathy, optical coherence tomography angiography, foveal avascular zone

Yusuke Arai,1 Yukihiro Sato,1 Atsushi Yoshida,1 Hidetoshi Kawashima,1 Toshikatsu Kaburaki,2 Harumi Gomi3 1Department of Ophthalmology, Jichi Medical University, Tochigi, Japan; 2Department of Ophthalmology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan; 3Center for Clinical Infectious Diseases, Jichi Medical University, Tochigi, Japan Purpose: Candida albicans subretinal abscess is extremely rare. To our knowledge, only one unilateral case has been reported. Herein, we report one bilateral case. Mixed bacterial infection was also suspected based on broad-range real-time polymerase chain reaction.Methods: A 64-year-old man being treated with oral corticosteroids for interstitial pneumonia visited us for visual loss in the left eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and 8/200 in the left eye. Funduscopy revealed round yellowish-white subretinal lesions with retinal hemorrhage in both eyes.Results: Broad-range polymerase chain reaction of the vitreous fluid from the left eye showed a high copy count of bacterial 16s ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision decreased to light perception in the left eye. Exenteration of the left eye was performed followed by microscopic examination showing Gram-negative bacilli, and C. albicans was also cultured. Antibiotics and the maximum doses of antifungal drugs were administered. However, the abscess in the right eye expanded, and BCVA decreased to 2/200. Vitrectomy and silicone oil tamponade were performed. Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was stable at 4/200 with healing of the subretinal abscess under silicone oil.Conclusion: Since C. albicans subretinal abscess is extremely rare and there was a concurrent mixed bacterial infection, diagnostic procedures in our bilateral case were more complicated than usual. C. albicans infection should be included in the differential diagnosis of subretinal abscesses. Keywords: Candida albicans, subretinal abscess, mixed infection

Aims: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. Methods: One hundred and twenty [...]

Clinicians should be aware of thyroid eye disease when a patient presents with lid swelling and diplopia following COVID-19 vaccination. Learning points for clinicians Coronavirus disease 2019 (COVID-19) vaccine administration may be considered a triggering factor for thyroid autoimmune disorders. [Extracted from the article]

Presents a letter to the editor referring to an article on bleb-related endopthalmitis caused by group B streptococcus, previously published in the July 2003 issue of the periodical.

Purpose: This study aimed to investigate the clinical characteristics, diagnostic markers, and treatment outcomes of varicella-zoster virus-associated anterior uveitis (VZV-AU) with and without ophthalmic herpes zoster (herpes zoster ophthalmicus (HZO) and zoster sine herpete (ZSH), respectively)., Methods: Clinical records of 47 VZV-AU patients (21 ZSH, 26 hZO) were retrospectively reviewed for clinical findings, medication use, and PCR using aqueous humor (AH) results., Results: There was no significant difference in age, gender, visual acuity (VA), or intraocular pressure (IOP) between the two groups. At the initial visit, small-to-medium white keratic precipitates (KPs) were significantly more observed in ZSH group than in HZO group, although there was no significant difference in the frequencies of other ocular findings between the two groups. Early antiviral medication use was significantly higher in HZO group (96.2%) than in ZSH group (19.1%). PCR was performed in 85.7% of ZSH and 53.8% of HZO patients. VZV-DNA positivity and viral load were similar between groups. Multivariate analysis revealed a positive correlation between white KPs and VZV viral load in AH. Although the ultimate use of antiviral medication was still less in ZSH group (71.4%), there were no significant differences in VA and IOP at the last visit between the two groups., Conclusion: Patients with ZSH had more white KPs and received less early antiviral medication than those with HZO. However, visual outcomes were similar between the two groups. Small-to-medium white KPs were significantly associated with the viral load of VZV in AH, suggesting that they could be an active marker.

Purpose: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients., Methods: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated., Results: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%., Conclusions: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.

Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.

Intraocular lymphoma (IOL) is a rare malignant intraocular lymphocytic tumor that mimics uveitis. IOL is anatomically classified into vitreoretinal lymphoma (VRL) and uveal lymphoma; most IOLs are VRLs, while uveal lymphoma is rare. VRL is highly malignant, with 60%-85% of patients developing central nervous system (CNS) lymphoma; primary VRL (PVRL) is an ocular disease with poor prognosis. We aimed to review the management and both current and future treatments for VRL. VRL diagnosis is based on the results of cytopathological examination using vitreous biopsy. However, the positive ratio of vitreous cytology remains 29%-70%. A combination of adjunctive tests may improve diagnostic accuracy, but as yet no gold-standard regimen has been established. Methotrexate intravitreal injections are effective in controlling ocular lesions; however, this treatment allows CNS dissemination. The efficacy of systemic chemotherapy in suppressing CNS dissemination has been recently debated. A multicenter prospective study with a unified treatment protocol is required to clarify this issue. In addition, establishing a treatment protocol for elderly patients and those with poor general health is necessary. Moreover, relapsed/refractory VRL and secondary VRL are more difficult to treat than PVRL because they are prone to recurrence. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are promising treatments for relapsed/refractory VRL. In Japan, Bruton's tyrosine kinase (BTK) inhibitors have been approved for treating refractory CNS lymphoma. Furthermore, a randomized prospective study of tirabrutinib, a highly selective BTK inhibitor, is ongoing for evaluating the suppressing of CNS progression in patients with PVRL., (© 2023. Japanese Ophthalmological Society.)

Purpose: The purpose of this study was to investigate the impact of prostaglandin D2 (PGD2) receptor 2 (DP2) on choroidal neovascularization (CNV) formation in mice., Methods: Using a laser-induced CNV model, the CNV size of wild-type (WT) mice treated with DP2 antagonist (CAY10471 or OC000459) was compared with that of untreated mice. Vascular endothelial growth factor (VEGF) and MCP-1 levels were also compared between the two groups. Similar experiments were performed comparing DP2 knockout (DP2KO) mice with WT mice (8 and 56 weeks old). The number of infiltrating macrophages to laser spots was also compared between the WT and DP2KO mice. We administered a DP2 antagonist to 15-methyl PGD2 (a DP2 agonist)-stimulated ARPE-19 cells and measured VEGF secretion by enzyme-linked immunosorbent assay. Tube formation assay was performed on human umbilical vein endothelial cells with or without a DP2 antagonist., Results: CNV sizes were significantly smaller in mice treated with CAY10471 or OC000459 than in those treated with vehicle. Similarly, the CNV size of DP2KO mice was significantly smaller than that of WT mice. The number of macrophages at laser spots in DP2KO mice was significantly lower than that in WT mice. The VEGF concentration of lasered DP2KO mice's eyes was significantly lower than that of lasered WT mice' eyes. DP2 antagonist treatment suppressed VEGF secretion in ARPE-19 cells under 15-methyl PGD2 stimulation. The tube formation assay suggested that lumen formation was inhibited by a DP2 antagonist., Conclusions: DP2 blockade attenuated choroidal neovascularization., Translational Relevance: Drugs targeting DP2 are potentially a novel treatment for age-related macular degeneration.

Purpose: We report and verify a novel hue discrimination instrument. We also investigate its efficiency to determine hue discrimination in persons with normal color vision., Study Design: Experimental and clinical investigation., Method and Study Participants: The instrument setup comprises an optical unit and examination unit. The optical unit is composed of the same 2 spectrometers and their controllers, which enables the independent emission of different spectral lights. Two independent bundle fibers connect the optical unit and the examination unit. Two different wavelength lights are illuminated on the bipartite upper and lower circular objectives with a visual angle of 2 degrees in the examination unit. The examinee recognizes the difference in the spectral lights between the bipartite targets. Persons with normal color vision are examined and the findings are confirmed using the Ishihara Test for Colour Deficiency., Results: The instrument could generate spectral light from 450 to 650 nm within 2-nm accuracy. The spectral light showed a different light intensity according to the spectral centroid, ranging from 450 to 650 nm, but the difference could be adjusted and was negligible in terms of determination of hue discrimination using the power meter. Three width slits, 0.2 mm, 0.5 mm, and 1.0 mm, to homogenize the light path were investigated. The half-width wavelength was accurate on each spectral centroid; however, the 0.5 mm slit was suitable to generate an efficient light path. The hue discrimination differed among the study participants. In general, at short and long wavelength lights, the hue discrimination range was large: about 15 nm at 450 nm and about 10 nm at 650 nm. Between 470 and 620 nm, the hue discrimination showed good sensitivity and specificity between 8 and 2 nm depending on the targeting wavelength lights. Intraindividual variation was small, ranging from 3 to 1 nm, thus indicating good repeatability. The time to examine the hue discrimination was about 20 min., Conclusion: This newly invented instrument using two independent spectrometer units enabled the determination of hue discrimination. The instrument's sensitivity and specificity including its repeatability were confirmed and indicated that the instrument could be a clinically applicable method., (© 2023. Japanese Ophthalmological Society.)

Rationale: Satoyoshi syndrome is a rare systemic autoimmune disease that presents with painful muscle spasms. We report a case of impending central retinal vein occlusion (CRVO) secondary to granulomatous pan-uveitis in a 32-year-old woman with Satoyoshi syndrome., Patient Concerns: At the age of 7 years, she developed generalized hair loss and painful spasms and was diagnosed with Satoyoshi syndrome. Her current symptoms included sudden metamorphopsia and decreased visual acuity in the left eye. She visited our hospital with extensive intraretinal hemorrhage (including the macula), meandering of the retinal veins, and swelling of the optic disc. Fluorescence fundus angiography demonstrated hyper fluorescence of the optic disc and leakage from the retinal veins, suggesting CRVO associated with optic papillitis and segmental periphlebitis., Diagnoses: In the left eye, there were 2 + cells in the anterior chamber and 1 + in the anterior vitreous., Interventions: We increased the existing dose of prednisolone for the treatment of uveitis and started her on oral aspirin and kallidinogenase for CRVO., Outcomes: The impending CRVO gradually subsided, and her visual acuity improved. However, during the subsequent treatment course, angle nodules were observed in the left eye, and the intraocular pressure (IOP) gradually increased. Although the angled nodules disappeared with topical corticosteroid treatment, the IOP did not reduce and became uncontrolled. Therefore, we performed trabeculotomy first, followed by trabeculectomy, after which the IOP decreased to approximately 10 mm Hg., Lessons: Unilateral granulomatous pan-uveitis and impending CRVO were observed in this patient. Several cases of Satoyoshi syndrome complicated by various autoimmune or immunological disorders have been reported. However, to the best of our knowledge, no reports of Satoyoshi syndrome presenting with uveitis or CRVO have been published. Physicians should consider uveitis as a complication of Satoyoshi syndrome., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination., Design: Matched cohort and self-controlled case series (SCCS) studies., Participants: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events., Methods: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods., Main Outcome Measures: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis., Results: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively., Conclusions: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Herpetic anterior uveitis (AU) is usually caused by the herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Herein, we report a case of herpetic AU associated with human herpesvirus 7 (HHV-7) infection., Study Design: A case report., Case Presentation: A 49-year-old female patient presented with complaints of blurred vision and hyperemia in the right eye. Slit-lamp examination revealed bilateral fine and a few small white keratic precipitates (KPs), Descemet membrane folds in the right eye, and severe and mild cellular infiltration in the anterior chamber of the right and left eye, respectively. HHV-7 viral DNA was detected by a polymerase chain reaction assay of an aqueous humor sample. The AU improved significantly with topical steroids., Conclusion: We report a rare case of herpetic AU characterized by fine and small white KPs in which only HHV-7 DNA was detected in the aqueous humor.

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., (© 2022. Japanese Ophthalmological Society.)

Granular cell tumours (GCTs) are benign tumours that rarely develop in intraocular regions. We report a rare case of intraocular GCT in the ciliary body. A woman in her 20s with a history of bone marrow transplantation for malignant lymphoma in early childhood was referred to our department for bilateral proliferative diabetic retinopathy. A yellowish-white ciliary tumour was observed in the temporal periphery of the patient's left eye during routine ophthalmological examination. As the tumour enlarged, we performed total resection combined with vitrectomy, silicone oil tamponade and cataract surgery. Histopathological examination revealed tumour cells with small, round or oval nuclei with eosinophilic cytoplasm. Positive immunohistochemical staining for S-100 and vimentin led to a diagnosis of ciliary GCT. No retinal detachment, proliferative membrane formation or tumour recurrence was observed 4 years postoperatively. Intraocular GCT should be considered a differential diagnosis of ciliary tumours., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF)., Methods: Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed., Results: The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%., Conclusion: ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Ophthalmology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest., (Copyright © 2022 Shirane, Yawata, Motooka, Shibata, Khor, Omae, Kaburaki, Yanai, Mashimo, Yamana, Ito, Hayashida, Mori, Numata, Murakami, Fujiwara, Ohguro, Hosogai, Akiyama, Hasegawa, Paley, Takeda, Maenaka, Akashi, Yokoyama, Tokunaga, Yawata and Sonoda.)

Objectives: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease., Methods: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients., Results: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10 -8 ). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10 -8 ), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10 -7 ), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients., Conclusions: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan., Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively., Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit., Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoneda, Usui, Tanaka, Hase, Namba, Kamoi, Takase, Takeuchi, Matsumiya, Kusuhara, Takeda, Yawata, Yanai, Hiyama, Harada, Hashida, Maruyama, Nakai, Taguchi, Kaburaki, Mizuki, Goto, Fujino and Takeuchi.)

Purpose: The aim of this study was to investigate the effects of different anesthetic agents on electroretinograms (ERGs) in Spontaneously Diabetic Torii fatty rats (SDT fatty rats)., Methods: The ERG recordings were measured under general anesthesia using pentobarbital or a combination of medetomidine hydrochloride, midazolam, and butorphanol (MMB) tartrate anesthesia in 12 9-week-old normal Sprague-Dawley rats (Jcl:SD rats) and 16 SDT fatty rats. Each animal model was divided into 2 groups, the pentobarbital group and MMB group. The amplitudes and peak times of the a- and b-waves and oscillatory potentials (OPs) were measured from 0.0001 candela per square meter (cd.s/m 2 ) to 10.0 cd.s/m 2 ., Results: The amplitude of the a-wave was significantly higher in the MMB group of Jcl:SD rats, but there was no significant difference in amplitude between the two groups of SDT fatty rats. There was no significant difference in the OP1 amplitude between both groups of Jcl:SD rats, but the OP1 amplitude was significantly higher in the MMB group of SDT fatty rats. The OP2 amplitude was significantly higher in the pentobarbital group in both the Jcl:SD rats and SDT fatty rats. There was no significant difference in the OP3 amplitude between the Jcl:SD and SDT fatty rat groups. The amplitude of the OP4 waves was significantly higher in the MMB group for both Jcl:SD and SDT fatty rats. There was no significant difference in the sums of the OP1 to OP4 (ΣOPs) amplitudes between the Jcl:SD and SDT fatty rat groups. There was no significant difference in the b-wave amplitude between the Jcl:SD rat groups, but the b-wave amplitude was significantly higher in the SDT fatty rats that received pentobarbital. The peak times for a-wave, OP1, OP2, OP3, OP4, and ΣOPs were significantly longer in the pentobarbital group of SD rats. The peak time of the b-wave was significantly longer in the MMB group of Jcl:SD rats, but the same result was obtained in the SDT fatty rats except that there was no significant difference in the a-wave., Conclusion: The overall ERG results vary depending on the anesthetic agent used. The OPs can be observed in detail when using MMB. Since the SDT fatty rat is a diabetic model animal, we recommend MMB as the anesthesia of choice when studying the OP waves in detail., Competing Interests: All authors declare that there are no conflicts of interest regarding the publication of this paper. Shinohara and Kageyama are employees of CLEA Japan, Inc. Sasase is an employee of Japan Tobacco Inc., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Purpose: To establish diagnostic criteria for vitreoretinal lymphoma (VRL) using cytology and laboratory tests from vitreous samples: interleukin (IL)-10/IL-6 ratio, immunoglobulin (Ig) H gene rearrangement, and clonal B-cells on flow cytometry., Methods: Fifty-six patients with and 39 without VRL were included. We assessed the sensitivity and specificity of each test and those of diagnostic criteria based on combinations of these tests., Results: The sensitivity values for malignant cytology, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry were 0.554, 0.821, 0.732, and 0.625 with specificity of 1.000, 1.000, 0.846, and 0.974, respectively. When the diagnostic criteria were set at malignant cytology or at two or more of of four tests (atypical cells, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry), the sensitivity and specificity values for accurate diagnosis were 0.929 and 1.00, respectively., Conclusion: Malignant cytology or positive results for two or more of four tests may be adequate for VRL diagnosis.

Introduction: The aim of this nationwide, prospective post-marketing surveillance was to assess the safety and effectiveness of up to 52 weeks of adalimumab treatment in patients with noninfectious intermediate, posterior, or panuveitis in Japanese clinical practice., Methods: This post-marketing surveillance was conducted at 60 medical facilities in Japan from October 2016 to June 2020. Patients with noninfectious intermediate, posterior, or panuveitis who were administered adalimumab (Humira ® , AbbVie Inc.) for the first time were eligible. Subcutaneous adalimumab was initially administered at 80 mg, followed by 40 mg 1 week later, then 40 mg every 2 weeks. Safety measures included the incidence of adverse events (AEs) and adverse drug reactions (ADRs; primary endpoint). Effectiveness measures included visual acuity, anterior chamber cell grade, vitreous haze, macular edema, foveal retinal thickness, uveitis recurrence rate, and oral corticosteroid dose. Health-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25)., Results: During 52 weeks of surveillance, AEs and ADRs occurred in 70 (27.9%) and 47 (18.7%) of 251 patients, respectively. The most common ADR was infection (21/251 patients; 8.4%), including serious infections in eight (3.2%) patients. ADRs were more frequent in patients ≥ 65 years of age, those with concurrent diseases, and those with past medical history. Four patients developed tuberculosis. The uveitis recurrence rate was 24.8% (61/246 patients). All effectiveness measures tended to improve from baseline to week 52, and mean corticosteroid doses decreased. Clinically meaningful changes were observed for most VFQ-25 subscales., Conclusions: The safety profile of adalimumab was generally consistent with previous reports, and no new safety concerns were identified., Trial Registration: ClinicalTrials.gov: NCT02916017., (© 2022. The Author(s).)

Differential diagnosis of lens dislocation includes various ocular and systemic diseases, as well as a history of trauma. The purpose of this study is to report cases of lens dislocation caused by family violence, a social problem that is increasing worldwide. Case 1: a 70-year-old female with narrow anterior chamber and high intraocular pressure in her left eye due to lens dislocation was referred to our hospital after her husband had beaten her with a fist. She explained to the previous doctor that she had hit her eye by herself. Case 2: a 99-year-old female with in-the-bag intraocular lens (IOL) dislocation in her left eye 10 years after receiving cataract surgery was referred to our hospital. The following year, she was referred to our hospital because the same incident occurred in her right eye. She explained to the previous doctor that she had fallen but was found to be due to family violence. Case 3: a 62-year-old female suffered dislocation of an IOL inserted in her left eye 10 years previously. While her explanation to the referring doctor was that she tumbled and fell, further inquiry revealed family violence to be the cause. In conclusion, lens dislocation may be caused by family violence despite a conflicting initial clinical history., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)