Intuitive Cell Manipulation Microscope System with Haptic Device for Intracytoplasmic Sperm Injection Simplification.

In recent years, the demand for effective intracytoplasmic sperm injection (ICSI) for the treatment of male infertility has increased. The ICSI operation is complicated as it involves delicate organs and requires a high level of skill. Several cell manipulation systems that do not require such skills have been proposed; notably, several automated methods are available for cell rotation. However, these methods are unfeasible for the delicate ICSI medical procedure because of safety issues. Thus, this study proposes a microscopic system that enables intuitive micropipette manipulation using a haptic device that safely and efficiently performs the entire ICSI procedure. The proposed system switches between field-of-view expansion and three-dimensional image presentation to present images according to the operational stage. In addition, the system enables intuitive pipette manipulation using a haptic device. Experiments were conducted on microbeads instead of oocytes. The results confirmed that the time required for the experimental task was improved by 52.6%, and the injection error was improved by 75.3% compared to those observed in the conventional system.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Classification of Peripheral Blood Leukocyte Phenotypes and Serum Cytokines in Vogt-Koyanagi-Harada Disease before and after Glucocorticoid Therapy.

Vogt-Koyanagi-Harada disease (VKH) is an autoimmune disease, and glucocorticoid therapy (GC) is widely used for VKH. We provided a profile of leukocyte populations and serum cytokines in VKH patients under GC. A prospective observational study was conducted on three treatment-naïve VKH patients. Peripheral blood samples were collected from the patients before GC (VKH-acute) and after 6 months (VKH-remission), and healthy individuals were used as controls. Proportions of 37-type leukocytes and levels of 27-kind cytokines were measured by mass cytometry and multiplex bead analysis. Property similarity was analyzed using hierarchical cluster analysis. The leukocytes and cytokines were broadly classified into four and three clusters: (1) a cluster with high intensity in VKH-acute consisting of B cells, Th2-like, Th17-like, basophils, and IL-7 and IP-10; (2) a cluster with high intensity in VKH-remission composed of monocytes, neutrophils, IL-4, and TNFα; in leukocytes, (3) a cluster with low intensity in VKH-acute and -remission consisting of CD8+ T cells, Th1-like, and NKT cells; (4) a cluster with low intensity in VKH-remission composed of NK cells, Tregs, and DCs; and in cytokines, (5) a cluster with high intensities in VKH-acute and -remission comprising G-CSF, MCP-1, eotaxin, and IL-17A. These findings suggest that inflammatory composition in blood during the acute phase of VKH represents complex hyperimmune responses dominantly driven by Th and B cells.

Ocular candidiasis in a tertiary hospital in Japan: A 10-year single-center retrospective study.

Ocular candidiasis is a major complication of candidemia that is sometimes sight-threatening. Although prompt ophthalmologic consultation and antifungal medication have been emphasized, recent changes in the causative species and drug susceptibilities make the picture unclear. This study aimed to determine whether there are trends among patients with ocular candidiasis and included 80 patients with candidemia who underwent ophthalmological screening at our hospital between 2010 and 2020. Data on the clinical characteristics, comorbidities, biochemical test results, causative Candida species, treatment, outcomes, visual acuity, and antifungal susceptibility were collected and analyzed. Statistical analyses were performed by comparing two groups, namely, the ocular candidiasis (n = 29) and non-ocular candidiasis (n = 51) groups. In the ocular candidiasis group, there were significantly more cases of central venous catheter insertion (82.8%, p = 0.026) and Candida albicans candidemia (72.4%, p < 0.001). Regarding ocular involvement, the majority of patients were asymptomatic. Most cases improved with antifungal therapy, but one case underwent vitrectomy. Between 2016 and 2020, there was a diversification of species, with a decrease in Candida parapsilosis and the emergence of Candida glabrata and Candida tropicalis. Regarding drug susceptibility, the minimum inhibitory concentrations of echinocandin and 5-fluorocytosine against Candida albicans, Candida parapsilosis, and Candida glabrata were slightly increased. In conclusion, in addition to appropriately performing ophthalmologic examinations, it is beneficial to select antifungal agents according to the diversity of species and drug susceptibilities.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Association between Systemic Factors and Vitreous Fluid Cytokines in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Systemic and intraocular factors are intricately related to PDR, and vitreous fluid (VF) cytokines are representative intraocular biomarkers. However, the associations between systemic factors and VF cytokines and their influence on PDR pathology are unclear. This study aimed to examine the correlation between systemic factors and VF cytokines and analyze their contributions to the pathology of PDR using multivariate analyses. We conducted a retrospective observational study on 26 PDR eyes of 25 patients with type 2 DM, and 30 eyes of 30 patients with idiopathic macular hole or epiretinal membrane as controls. Fifteen systemic and laboratory tests including blood pressure (BP) and body mass index (BMI), and 27 cytokines in VF were analyzed. BP and BMI correlated positively with VF levels of IL-6 and IP-10 in PDR patients, while no significant correlation was found between systemic factors and VF cytokines in controls. MCP-1 and VEGF-A in VF separately clustered with different systemic factors in controls, but these cytokines lost the property similarity with systemic factors and acquired property similarity with each other in PDR. Systemic factors contributed to only 10.4%, whereas VF cytokines contributed to 42.3% out of 52.7% variance of the whole PDR dataset. Our results suggest that intraocular factors play a major role in the pathology of PDR, whereas systemic factors may have limited effects, and that BP and BMI control in PDR could be useful interventions to improve intraocular immune condition.

Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role.

BACKGROUND: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. PURPOSE: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. METHODS: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. RESULTS: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. CONCLUSION: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

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.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

A Case of Acute Retinal Necrosis Associated with Reactivation of Varicella Zoster Virus after COVID-19 Vaccination.

PURPOSE: To report a case of acute retinal necrosis (ARN) after receiving COVID-19 vaccination. METHODS: A case report. RESULTS: A 78-year-old man complained of blurred vision and floaters in the right eye 2 days after receiving BNT162b2 mRNA-based COVID-19 vaccine and was referred to our hospital with worsening visual acuity after 7 days. He had no systemic symptoms and no history of systemic diseases. Ophthalmic examination revealed white-yellowish placoid lesions spreading to the entire circumference of the retina, and temporal and upper lesions extending to the posterior pole, although anterior inflammation and vitreous opacity were mild. Diagnostic and therapeutic vitrectomy was performed, and VZV-DNA was detected by comprehensive PCR using a vitreous fluid sample. The ocular inflammation subsided by systemic administration of antivirals and corticosteroids. However, total retinal detachment requiring repeat vitrectomy using silicone oil occurred after the second vaccination. CONCLUSION: ARN associated with VZV reactivation may develop after SARS-CoV-2 mRNA vaccination.

Ischemic Retinopathy with Vitreous Hemorrhage Resembling Diabetic Retinopathy in a Patient with Mixed Cryoglobulinemia.

PURPOSE: To report a case of mixed cryoglobulinemia manifesting retinopathy with bilateral vitreous hemorrhage (VH) resembling diabetic retinopathy. CASE REPORT: A 60-year-old Japanese man with renal dysfunction of unknown origin was hospitalized for investigation of underlying disease. Laboratory examinations were positive for cryoglobulins composed of IgG and IgM in serum, and hepatitis C virus (HCV) infection. He was diagnosed with HCV-related mixed cryoglobulinemia. During hospitalization, he developed sudden loss of vision and was referred to the department of ophthalmology. Ophthalmic examination revealed VH in both eyes, and vitrectomy was performed on the right eye. Fundus examination after vitrectomy revealed sheathing vessels, mottled hemorrhages in the entire retina, and avascular areas with neovascularization. Disrupted outer retinal layers in the macula were confirmed. Vitreous fluid level of VEGF-A in the right eye was 166.6 pg/mL. CONCLUSION: Retinal ischemia resembling diabetic retinopathy may cause VH in patients with mixed cryoglobulinemia.

Clinical relevance of fibrin membranous structures in the intra-photoreceptor outer segment separation on spectral domain optical coherence tomography (SD-OCT) in initial-onset acute Vogt-Koyanagi-Harada disease.

PURPOSE: The purpose of the study was to investigate clinical relevance of fibrin membranous structure (FMS) in the photoreceptor outer segments on spectral-domain optical coherence tomography (SD-OCT) in untreated initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts of 39 patients (78 eyes) diagnosed with initial-onset VKH disease were retrospectively reviewed. Age, gender, period from the onset of symptoms to first visit, visual acuity (VA), intraocular pressure (IOP), anterior chamber cells, serous retinal detachment (SRD), SD-OCT findings, as well as fluorescein (FA), and indocyanine green angiography (ICGA) were collected. RESULTS: FMS was observed in 24 out of 39 VKH patients in either eye (61.5%). VKH patients with FMS (FMS group) were significantly younger and had the shorter period from the onset of symptoms to the first visit compared with those without FMS (non-FMS group). Mean logMAR VA and proportion of pooling of dye, mean central retinal thickness (CRT) were significantly higher in FMS group than in non-FMS group. In contrast, hyperfluorescence of the optic disc on FA was more in non-FMS group than in FMS group. Significant positive correlations between CRT and logMAR VA or IOP were only observed in the FMS group. Total amount of corticosteroids was significantly greater in FMS group than in non-FMS group. However, there were no significant differences in LogMAR VA and IOP between two groups at 6 months after treatment initiation. CONCLUSION: FMS on SD-OCT is a critical feature observed in the early stage of initial-onset acute VKH disease, which is more common in younger patients and is related to the disease activity.

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.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Epidemiology and characteristics of common forms of anterior uveitis at initial presentation in a tertiary facility in Japan.

PURPOSE: To elucidate detailed epidemiological profile of common types of anterior uveitis (AU) in real-world clinical setting of a tertiary facility in Japan, and to evaluate the characteristic clinical findings at initial presentation. STUDY DESIGN: Retrospective cohort study. METHODS: Clinical charts of 275 patients (335 eyes) aged 52.5 ± 19.1 years were reviewed retrospectively. Herpetic AU was diagnosed by multiplex polymerase chain reaction tests using aqueous humor. Time of uveitis onset, gender, laterality, disease course since the initial onset of AU, visual acuity (VA) and intraocular pressure (IOP) at first visit, and definitive diagnosis were collected from clinical charts. RESULTS: Acute AU (AAU) was the most common (21.8%) form of AU; followed by herpetic AU (20.7%) comprising Herpes Simplex Virus (HSV) (8.0%), Varicella Zoster Virus (VZV) (9.1%) and cytomegalo virus (CMV) (3.6%); scleritis (13.5%); diabetic iritis (7.6%), and Posner-Schlossman syndrome (5.5%). Unilateral AU constituted 78.2%, and VA less than 20/30 accounted for 31.2%. Of all the eyes, 16.1% had an IOP higher than 20 mmHg, out of which 37.0% had herpetic AU, followed by scleritis in 25.9%, and Posner-Schlossman syndrome (PSS) in 11.1%. AU patients over 60 years of age were 40.4%, in which 34.2% had herpetic AU, followed by scleritis in 14.4% and AAU in 13.5%. Herpetic AU patients were significantly older and had higher IOP compared with AAU patients. CONCLUSION: The most frequent AU was AAU, followed by herpetic AU. Herpetic AU patients were older and had higher intraocular pressure than AAU patients, although VA was equally impaired in both groups.

Auditory Feedback for Enhanced Sense of Agency in Shared Control.

There is a growing need for robots that can be remotely controlled to perform tasks of one's own choice. However, the SoA (Sense of Agency: the sense of recognizing that the motion of an observed object is caused by oneself) is reduced because the subject of the robot motion is identified as external due to shared control. To address this issue, we aimed to suppress the decline in SoA by presenting auditory feedback that aims to blur the distinction between self and others. We performed the tracking task in a virtual environment under four different auditory feedback conditions, with varying levels of automation to manipulate the virtual robot gripper. Experimental results showed that the proposed auditory feedback suppressed the decrease in the SoA at a medium level of automation. It is suggested that our proposed auditory feedback could blur the distinction between self and others, and that the operator attributes the subject of the motion of the manipulated object to himself.

A New Pharmacological Vitreolysis through the Supplement of Mixed Fruit Enzymes for Patients with Ocular Floaters or Vitreous Hemorrhage-Induced Floaters.

Purpose: Ocular floaters caused by vitreous degeneration or blood clots may interfere with various visual functions. Our study investigated the pharmacologic effects of oral supplementation of mixed fruit enzymes (MFEs) for treating spontaneous symptomatic vitreous opacities (SVOs) and those secondary to vitreous hemorrhage (VH). Methods: 224 patients with monocular symptomatic vitreous opacities (SVOs) were recruited between September and December 2017 and received oral supplementation of MFEs (190 mg bromelain, 95 mg papain, and 95 mg ficin) for 3 months in a double-blind clinical trial. Participants were divided according to the etiology of the SVOs, spontaneous (experiment 1) versus VH (experiment 2), and then randomly assigned into four treatments groups: one group received oral vitamin C, as a placebo; and the other 3 groups received 1 capsule per day (low dose), 2 capsules per day (middle dose), or 3 capsules per day (high dose) of MFEs. The number of SVOs was determined at baseline and then 1, 2, and 3 months after initiating treatment. Further, in cases secondary to VH, the changes in corrected distance visual acuity (CDVA) were assessed after 3 months. Second, we compared the free radical scavenging capabilities of each substance: vitamin C, bromelain, papain, ficin, and MFEs (combination of bromelain, papain, and ficin) by DDPH assay. Finally, SVOs-related symptoms and satisfaction with the treatments were evaluated at the last follow-up visit Results: In experiment 1, the disappearance rate of SVOs was 55%, 62.5%, and 70% after taking 1, 2, and 3 capsules daily, respectively (total p < 0.001), in a dose-dependent manner. In experiment 2, the disappearance rate of VH-induced SVOs was 18%, 25%, and 56% (p < 0.001) after 1, 2, and 3 capsules of the supplement daily, respectively. Additionally, the patients' vision elevated from 0.63LogMAR to 0.19LogMAR (p = 0.008). Conclusions: A pharmacological approach using a high dose of oral supplementation with MFEs (bromelain, papain, and ficin) was effective in reducing vitreous opacities, even after intraocular hemorrhage. Furthermore, pharmacologic vitreolysis with MFEs supplementation showed high patient satisfaction, and also improved CDVA in patients with vitreous hemorrhage-induced floaters

Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious pandemic. COVID-19 vaccination is urgent needed for limiting SARS-CoV-2 outbreaks by herd immunity. Simultaneously, post-marketing surveillance to assess vaccine safety is important, and collection of vaccine-related adverse events has been in progress. Vision-threatening ophthalmic adverse events of COVID-19 vaccines are rare but are a matter of concern. We report a 45-year-old Japanese male with positive for HLA-DR4/HLA-DRB1*0405, who developed bilateral panuveitis resembling Vogt-Koyanagi-Harada (VKH) disease after the second dose of Pfizer-BioNTech COVID-19 mRNA (BNT162b2) vaccine. Glucocorticosteroid (GC) therapy combined with cyclosporine A (CsA) readily improved the panuveitis. The immune profile at the time of onset was analyzed using CyTOF technology, which revealed activations of innate immunity mainly consisting of natural killer cells, and acquired immunity predominantly composed of B cells and CD8+ T cells. On the other hand, the immune profile in the remission phase was altered by GC therapy with CsA to a profile composed primarily of CD4+ cells, which was considerably similar to that of the healthy control before the vaccination. Our results indicate that BNT162b2 vaccine may trigger an accidental immune cross-reactivity to melanocyte epitopes in the choroid, resulting in the onset of panuveitis resembling VKH disease.