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Introduction: Severe central visual field defects are frequently observed in highly myopic eyes. This report details 2 cases of central visual field defects in individuals with high myopia, characterized by an unusual temporal protrusion of the optic disc, a feature not previously documented. Case Presentation: Two patients, a 54-year-old man and a 65-year-old woman, were diagnosed with high myopia in their left eyes, displaying an outward protrusion of the optic disc toward the macula. Swept-source optical coherence tomography revealed a focal lamina cribrosa defect at the temporal edge of the protruding optic disc, corresponding to the papillomacular bundle area of retinal nerve fibers, which exhibited thinning around the focal lamina cribrosa defect. Visual field examination indicated a central visual field defect in the affected eyes, which pattern corresponded to the papillomacular bundle responsible area. Conclusion: The emergence of a temporal protrusion in the optic disc may lead to a focal lamina cribrosa defect, resulting in a central visual field defect in highly myopic eyes. This distinctive optic disc feature may constitute a critical risk factor for a central visual field defect. Hence, optic disc protrusion in high myopia warrants attention, necessitating careful ophthalmic examinations for central visual field defects.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

AIM: To explore the usage of choroidal thickness measured by swept-source optical coherence tomography (SS-OCT) to detect myopic macular degeneration (MMD) in high myopic participants. METHODS: Participants with bilateral high myopia (≤−6 diopters) were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. SS-OCT was performed to determine the choroidal thickness, and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia (META-PM) Classi?cation. Presence of MMD was defined as META-PM category 2 or above. RESULTS: A total of 568 right eyes were included for analysis. Eyes with MMD (n=106, 18.7%) were found to have older age, longer axial lengths (AL), higher myopic spherical equivalents (SE), and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector (P

Abstract The aim is to study the intraocular pressure (IOP)-lowering effects of additional administration of ripasudil in open-angle glaucoma (OAG) patients including high myopia (HM) and pathological myopia (PM). Study design is retrospective cohort study. We assessed the changes in the mean IOP between the HM eyes (axial length ≧ 26.5 mm 33 eyes) and the non-HM eyes (axial length

Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health.

Cytomegalovirus (CMV) retinitis is the most common eye disease associated with CMV infection in immunocompromised individuals. The CMVR may initially be asymptomatic; however, relatively mild vitreous inflammation at the onset may be an important differential point from other diseases in HIV patients. Fundus photography, CD4 T-cell count, and telemedicine could be used to screen and monitor the high-risk population, particularly in resource-limited regions. Retinitis generally starts in the peripheral retina and advances toward the posterior pole, which could develop to the characteristic “pizza pie” appearance marked by central retinal necrosis and intraretinal hemorrhage. CMVR causes vision loss if left untreated, and early antiviral therapy significantly reduces the risk of vision loss. Alongside traditional antiviral treatments, immunotherapies including CMV-specific adoptive T-cell therapy and CMV immunoglobulin (CMVIG) are emerging as promising treatment options due to their favorable tolerability and reduced mortality. This review comprehensively examines CMV retinitis, encompassing the clinical features, differential diagnosis, laboratory tests, and updated treatment strategies to inform clinical management.

Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.

(1) Background: The fundus examination is one of the best and popular methods in the assessment of vascular status in the human body. Direct viewing of retinal vessels by ophthalmoscopy has been utilized in judging hypertensive change or arteriosclerosis. Recently, fundus imaging with the non-mydriatic scanning laser ophthalmoscope (SLO) has been widely used in ophthalmological clinics since it has multimodal functions for optical coherence tomography or angiography with contrast agent dye. The purpose of this study was to examine the utility in detecting arteriosclerosis of retinal vessels in SLO images; (2) Methods: Both color and blue standard field SLO images of eyes with diabetic retinopathy (DR) were examined retrospectively. Retinal arteriosclerosis in color SLO images was graded according to the Scheie classification. Additionally, characteristics of retinal arterioles in blue SLO images were identified and examined for their relevance to arteriosclerosis grades, stages of DR or general complications; (3) Results: Relative to color fundus images, blue SLO images showed distinct hyper-reflective retinal arterioles against a monotone background. Irregularities of retinal arterioles identified in blue SLO images were frequently observed in the eyes of patients with severe arteriosclerosis (Grade 3: 79.0% and Grade 4: 81.8%). Furthermore, the findings on arterioles were more frequently associated with the eyes of DR patients with renal dysfunction (p < 0.05); (4) Conclusions: While color SLO images are equally as useful in assessing retinal arteriosclerosis as photography or ophthalmoscopy, the corresponding blue SLO images show arteriosclerotic lesions with high contrast in a monotone background. Retinal arteriosclerosis in eyes of advanced grades or advanced DR frequently show irregularities of retinal arterioles in the blue images. The findings of low, uneven, or discontinuous attenuation were easier to find in blue than in color SLO images. Consequently, blue SLO images can show pathological micro-sclerosis in retinal arterioles and are potentially one of the safe and practical methods for the vascular assessment of diabetic patients.

Abstract Background We retrospectively evaluate the long-term efficacy and safety of trabeculotomy glaucoma surgery in treating open-angle glaucoma (OAG) in eyes with high myopia (HM). Methods This study included 20 eyes with HM (axial length ≥ 26.5 mm) and OAG; age, preoperative IOP (intraocular pressure), and sex-matched 20 non-HM eyes (axial length

Purpose: To report our findings in a patient with a two layered dome shaped macula (DSM) in which only the inner layer of the sclera protruded anteriorly. Observations: An 84-year-old woman with high myopia had a DSM in both eyes. The optical coherence tomographic (OCT) image of the left eye showed a uniform thickening of the foveal sclera, but the DSM of the right eye was split into an inner and outer layer by intrascleral blood vessels running between the two layers. OCT showed that only the inner layer of the sclera protruded anteriorly while the outer layer remained in its normal position. Conclusions and importance: The two layered DSM suggests that the etiology of DSMs may be more complex.

We report a rare case of severe exudative retinal detachment with orbital granuloma associated with granulomatosis with polyangiitis (GPA). A 42-year-old man developed bilateral conjunctival hyperemia and eye pain 15 months before presenting to us. Because vitreous cells and retinal detachment were detected in his left eye, he was referred to us for further evaluation. The left eye showed scleral edema, cells in the anterior chamber and anterior vitreous, exudative retinal detachment, and elevated white subretinal lesions from the nasal to the inferior parts of the eye fundus. Orbital contrast-enhanced magnetic resonance imaging revealed a granulomatous lesion, retinal detachment, and fluid retention in the left eyeball. Comprehensive rheumatological evaluation revealed proteinase 3 anti-neutrophil cytoplasmic antibody positivity and a history of otitis media, leading to a GPA diagnosis. Methylprednisolone 1,000 mg/day was administered intravenously for 3 days, followed by oral prednisolone and intravenous cyclophosphamide. Although the retinal detachment decreased, scleritis and choroidal detachment relapse were observed in the left eye after the fifth cyclophosphamide administration. After switching from cyclophosphamide to rituximab, the scleritis and choroidal detachment resolved. Remission was successfully maintained with biannual rituximab administration. In this case, we conclude that rituximab was important to re-induce and maintain remission after recurrence. Collaboration with a rheumatologist is essential for proper treatment in related cases. This is the first report of ultra-widefield and multimodal imaging for retinal detachment associated with GPA.

Vaccination is a public health cornerstone that protects against numerous infectious diseases. Despite its benefits, immunization implications on ocular health warrant thorough investigation, particularly in the context of vaccine-induced ocular inflammation. This review aimed to elucidate the complex interplay between vaccination and the eye, focusing on the molecular and immunological pathways implicated in vaccine-associated ocular adverse effects. Through an in-depth analysis of recent advancements and the existing literature, we explored various mechanisms of vaccine-induced ocular inflammation, such as direct infection by live attenuated vaccines, immune complex formation, adjuvant-induced autoimmunity, molecular mimicry, hypersensitivity reactions, PEG-induced allergic reactions, Type 1 IFN activation, free extracellular RNA, and specific components. We further examined the specific ocular conditions associated with vaccination, such as uveitis, optic neuritis, and retinitis, and discussed the potential impact of novel vaccines, including those against SARS-CoV-2. This review sheds light on the intricate relationships between vaccination, the immune system, and ocular tissues, offering insights into informed discussions and future research directions aimed at optimizing vaccine safety and ophthalmological care. Our analysis underscores the importance of vigilance and further research to understand and mitigate the ocular side effects of vaccines, thereby ensuring the continued success of vaccination programs, while preserving ocular health.

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5–10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

Abstract The lamina cribrosa (LC) is a collagenous tissue located in the optic nerve head, and its dissection is observed in eyes with pathologic myopia as a LC defect (LCD). The diagnosis of LCD has been difficult because the LC is located deep beneath the retinal nerve fibers. The purpose of this study was to determine the prevalence and three-dimensional shape of LCDs in highly myopic eyes. Swept-source OCT scan images of a 3 × 3-mm cube centered on the optic disc were obtained from 119 eyes of 62 highly myopic patients. Each LC was manually labelled in cross-sectional OCT images along the axial, coronal, and sagittal planes. A deep convolutional neural network (DCNN) was trained with the manually labeled images, and the trained DCNN was applied to the detection of the LC in every image in each plane. Three-dimensional images of the LC were generated from the labeled image of each eye. The results showed that LCDs were detected in 12 of the 42 (29%) eyes in which an LC was visible. The LCDs ran vertically at the temporal edge of the optic disc. In conclusion, 3D OCT imaging with the application of DCNN is helpful in diagnosing LCDs.

mRNA COVID-19 vaccines have been reported as protecting against COVID-19 and reducing its severity, and we have recognized post-vaccination symptoms recently. This research investigates the clinical trajectories of ocular disorders in a 51-year-old female who received a second dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. Exhibiting fever and blurred vision within 24 h post-vaccination, with progressive blurry vision over two months, she underwent in-depth ophthalmologic examinations, revealing intraocular cellular infiltration in anterior chamber, vitreous opacity, and frosted branch angiitis in both eyes. Comprehensive evaluations, including systemic workups as well as ocular and blood specimen analyses, excluded autoimmune and infectious etiologies, consolidating the diagnosis of vaccine-induced ocular inflammation. Despite adherence to prevailing therapeutic protocols, her condition showed no significant improvement over 18 months, pointing to a possible long post-COVID vaccination syndrome. Such persistent sequelae underscore the need for detailed studies to discern the interactions between vaccine-induced immune responses and the development of post-vaccination sequelae. Continual documentation of patients with long post-COVID vaccination syndrome is now essential to better understand the vaccine’s immunological effects, aiding in improving global vaccination strategies.

Since the introduction of combination antiretroviral therapy (cART) in Japan in 2008, the spectrum of ocular manifestations in patients with human immunodeficiency virus (HIV) has changed. This study, conducted at Tokyo Medical and Dental University Hospital between January 2012 and August 2023, aimed to understand the epidemiology and clinical features of ocular manifestations in patients with HIV during the cART era. Of the 218 patients diagnosed with HIV, 23 (10.55%) exhibited ocular manifestations; all were male, aged 32–73. The most prevalent ocular complication was uveitis (60.67%). Notably, the prevalence of uveitis in this cART era has surged compared to earlier Japanese studies. Our data also suggest a potential direct link between uveitis and HIV, particularly in patients who have not yet undergone cART. However, cytomegalovirus retinitis, another prevalent ocular disease in our study, appeared more strongly associated with patients who commenced cART. Neither ocular condition was significantly correlated with CD4+ T-cell count. Importantly, our observed ocular manifestation prevalence (10.55%) was lower than that in previous studies, emphasizing the potential influence of cART and national healthcare support. These findings provide unique insights into the evolution of ocular manifestations in patients with HIV in Japan amidst cART availability.

Abstract The structure of the human vitreous varies considerably because of age-related liquefactions of the vitreous gel. These changes are poorly studied in vivo mainly because their high transparency and mobility make it difficult to obtain reliable and repeatable images of the vitreous. Optical coherence tomography can detect the boundaries between the vitreous gel and vitreous fluid, but it is difficult to obtain high resolution images that can be used to convert the images to three-dimensional (3D) images. Thus, the purpose of this study was to determine the shape and characteristics of the vitreous fluid using machine learning-based 3D modeling in which manually labelled fluid areas were used to train deep convolutional neural network (DCNN). The trained DCNN labelled vitreous fluid automatically and allowed us to obtain 3D vitreous model and to quantify the vitreous fluidic cavities. The mean volume and surface area of posterior vitreous fluidic cavities are 19.6 ± 7.8 mm3 and 104.0 ± 18.9 mm2 in eyes of 17 school children. The results suggested that vitreous fluidic cavities expanded as the cavities connects with each other, and this modeling system provided novel imaging markers for aging and eye diseases.

Abstract Little is known about the long-term incidence of posterior capsule opacification (PCO) after cataract surgery in patients with uveitis. This retrospective study included 211 eyes of 146 patients with non-infectious uveitis who underwent cataract surgery and implantation of an Acrysof SN60WF (Surface: plasma-treated, Optic and Haptic: hydrophobic acrylic), iSert XY-1 (Surface: UV-ozone-treated, Optic and Haptic: hydrophobic acrylic), or iSert 251/255 (Surface: UV-ozone-treated, Optics: hydrophobic acrylic, Haptic: polymethyl methacrylate). The cumulative incidences of PCO and subsequent yttrium–aluminum-garnet (Nd:YAG) capsulotomy over the 5-year follow-up were analyzed, and patients who were implanted with different intraocular lenses (IOLs) were compared. Mixed-effects Cox proportional hazard models showed that, compared with the Acrysof group, the iSert XY-1 group had higher risks of PCO (adjusted HR, 7.26; 95% CI, 1.82–28.8) and Nd:YAG capsulotomy (adjusted HR, 6.50; 95% CI, 1.55–27.2). Similar results were obtained when the Acrysof group was compared with the iSert 251/255 group for PCO (adjusted HR, 8.22; 95% CI, 2.35–28.7) and Nd:YAG capsulotomy (adjusted HR, 8.26; 1.90–36.0). These data suggest that a plasma-treated surface, hydrophobic acrylic optic and hydrophobic acrylic haptic, of the IOL could enhance biocompatibility even under inflammatory conditions, thus suppressing PCO development.

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.

IntroductionHTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1–associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti–vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF165, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro.MethodsWe used MT2 and TL-Om1 cells as HTLV-1–infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1–infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments.ResultsAnti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1–infected T cells.ConclusionThis preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1–related inflammation and thus may be safe for use.

Myopia most often develops during school age, with the highest incidence in countries with intensive education systems. Interactions between genetic variants and educational exposure are hypothesized to confer susceptibility to myopia, but few such interactions have been identified. Here, we aimed to identify genetic variants that interact with education level to confer susceptibility to myopia. Two groups of unrelated participants of European ancestry from UK Biobank were studied. A 'Stage-I' sample of 88,334 participants whose refractive error (avMSE) was measured by autorefraction and a 'Stage-II' sample of 252,838 participants who self-reported their age-of-onset of spectacle wear (AOSW) but who did not undergo autorefraction. Genetic variants were prioritized via a 2-step screening process in the Stage-I sample: Step 1 was a genome-wide association study for avMSE; Step 2 was a variance heterogeneity analysis for avMSE. Genotype-by-education interaction tests were performed in the Stage-II sample, with University education coded as a binary exposure. On average, participants were 58 years-old and left full-time education when they were 18 years-old; 35% reported University level education. The 2-step screening strategy in the Stage-I sample prioritized 25 genetic variants (GWAS P < 1e-04; variance heterogeneity P < 5e-05). In the Stage-II sample, 19 of the 25 (76%) genetic variants demonstrated evidence of variance heterogeneity, suggesting the majority were true positives. Five genetic variants located near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C had evidence of a genotype-by-education interaction in the Stage-II sample (P < 0.002) and consistent evidence of a genotype-by-education interaction in the Stage-I sample. For all 5 variants, University-level education was associated with an increased effect of the risk allele. In this cohort, additional years of education were associated with an enhanced effect of genetic variants that have roles including axon guidance and the development of neuronal synapses and neural circuits.

Abstract The purpose of this study was to determine the relationship between a posterior vitreous detachment (PVD) and retinoschisis (RS) in 73 highly myopic (HM) young patients age 16.4 ± 6.9 years and 24 non-HM children age 8.4 ± 1.5 years. The presence of the paravascular retinal abnormalities was determined in the images obtained by a ultra-widefield OCT (UWF OCT) instrument with an image field of 23 × 20 mm. The results showed that a partial PVD was detected in 15 (21%) of the HM patients, and the number increased significantly with increasing age (P = 0.02). PVDs of any type were not found in the non-HM eyes. The number of microvascular folds also increased with age in the HM patients (P = 0.03). Medium-reflective columnar tissues were present between the detached vitreous and inner retinal surface in 4 (5%) eyes of the HM patients. Myopic RS was found in 3 (4%) HM patients in the paravascular area but not in the macular area. These results suggest that early partial PVD may play a role in pathological and proliferative vitreous changes of HM eyes. An intense vitreoretinal traction with bridging tissues may cause the various paravascular retinal abnormalities. In HM eyes, paravascular RS is already present at an early age which may progress to macular RS with aging.

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified as the causative agent of human diseases, such as adult T-cell leukemia, HTLV-1-associated myelopathy, and HTLV-1 uveitis (HU). HU is one of the most frequent ocular inflammatory diseases in endemic areas, which has raised considerable public health concerns. Approximately 30% of HU patients develop secondary glaucoma, which is higher than the general uveitis incidence. We therefore investigated the mechanism underlying the high incidence of glaucoma secondary to HU in vitro. After contact with HTLV-1-producing T cells (MT-2), human trabecular meshwork cells (HTMCs) were infected. The infected cells increased in number, and nuclear factor (NF)-κB expression was activated. Contact between MT-2 cells and HTMCs resulted in significantly upregulated production of inflammatory cytokines, such as IL-6, and chemokines, such as CXCL10, CCL2, and CXCL-8. These findings indicate that the mechanism underlying secondary glaucoma in HU may involve proliferation of trabecular meshwork tissue after contact with HTLV-1-infected cells, resulting in decreased aqueous humor outflow. Upregulated production of inflammatory cytokines and chemokines simultaneously disrupts the normal trabecular meshwork function. This mechanism presumably leads to increased intraocular pressure, eventually resulting in secondary glaucoma.

Abstract Infliximab (IFX) was the first biologic introduced for refractory uveitis treatment in Behçet’s syndrome (BS). However, there have been few reports on the safety and efficacy of IFX monotherapy over follow-up periods of more than 10 years. This retrospective study evaluated the 10-year safety and efficacy of IFX monotherapy compared to IFX combination therapies with colchicine or corticosteroid for refractory uveitis in BS patients. Monotherapy was performed in 30 eyes of 16 patients while combination therapies were performed in 20 eyes of 11 patients. Continuation of IFX occurred in 70.3% of enrolled patients for 10 years without any significant difference noted in the retention rate between the monotherapy and combination therapies (p = 0.86). Reduction of ocular inflammatory attacks and improvement of best corrected visual acuity occurred in the monotherapy group after 10 years, which was equivalent to that for the combination therapies. Although adverse events (AEs) or therapy discontinuation occurred during the initial 5 years in both therapies, no AEs were observed for either therapy after 6 years. Our results suggested that IFX monotherapy proved to be effective and not inferior to combination therapies over a 10-year follow-up. Although loss of response and AEs may be noticed during the initial 5-year period, a safe and effective continuation can be expected thereafter.

The objective of this paper is to provide an overview of the World Health Organization - International Telecommunication Union MyopiaEd programme - a digital message programme targeting education on myopia and its prevention. The development of the MyopiaEd programme included 4 key steps: (1) Conceptualization and consultation with experts in the field of myopia, mHealth and health behavior change; (2) Creation of SMS message libraries and programme algorithm; (3) Review of the message libraries to ensure relevance to the target audience; and (4) Pre-testing amongst end-user groups to ensure that the design of the programme and the message content were understandable. After reviewing the available evidence and considering input of the experts, the aims, end users and key themes of the programme were finalized. Separate SMS-adapted message libraries were developed, reviewed and pre-tested for four target end-user groups; (1) general population involved in the care of children (2) parents or caregivers of children with myopia; (3) adolescents with myopia; and (4) adults with myopia. The message libraries are part of a comprehensive toolkit, developed through a consultative process with experts in digital health, to support implementation within countries. The development of the MyopiaEd programme aims to provide a basis for Member States and other stakeholders to develop, implement and monitor large-scale mHealth programmes. It is aimed at raising awareness of good eye care behaviors and addressing common reasons for non-compliance to spectacle wear. The next steps will involve adapting and evaluating the MyopiaEd programme in selected settings.

Purpose: To present our findings in a case of SO that developed in an eye with pathologic myopia. Observations: The patient was an 83-year-old woman who was examined one month after an ocular trauma to the right eye. She was found to have signs of uveitis with multiple serous retinal detachments in the non-injured contralateral left eye. In addition, she had hearing loss and mononuclear pleocytosis of the spinal fluids. Swept-source OCT images showed focal and choroidal thickening in areas with abrupt edges that was restricted to the regions with more normal appearing choroid. Bruch's membrane was damaged at the edge of the focal choroidal thickening. The ocular and systemic findings were rapidly resolved after systemic corticosteroid therapy. Conclusions and importance: The pathobiological and clinical course of SO is nearly identical to Vogt-Koyanagi Harada disease (VKH) although its pathogenesis of autoimmunity had not been definitively established. In eyes with pathologic myopia, the choroid is extremely thin and sometimes completely absent. The findings in this rare case indicate that in eyes with thin choroid, the OCT findings typical of SO might be different from those seen in non-highly myopic eyes. Thus, the pre-status of the choroid may affect the choroidal thickening in pathological conditions. This case gives us a valuable insight in understanding the pathology of SO and characteristic of pathologic myopia.

Abstract Background To report a rare case of pathologic myopia in which a choroidal neovascularization (CNV) induced a hemorrhagic macular hole retinal detachment (MHRD), and then both the CNV and MHRD disappeared simultaneously in 5 days. Case presentation A 76-year-old man with pathologic myopia complained of distorted vision in his left eye of 1-week duration. The visual acuity in the left eye was 20/20 and the axial length was 31.0 mm. Ophthalmoscopic examinations of the left eye showed many retinal hemorrhages and whitish lesions on a background of severe diffuse myopic atrophy. Swept-source OCT (SS-OCT) showed multiple hyperreflective vertical finger-like projections extending into the outer retina that corresponded to the area of the botryoidal-shaped retinal hemorrhages. The SS-OCT images also showed many subretinal infiltrations adjacent to linear retinal hemorrhages with a disruption of the adjacent ellipsoid zone of the photoreceptors. Fluorescein angiography (FA) showed early hyperfluorescence and late leakages corresponding to the areas of the hemorrhages or adjacent to the linear retinal hemorrhages. These results suggested that the development of the inflammatory CNV was related to the outer retinopathy or choroiditis as in eyes with punctate inner choroidopathy or multifocal choroiditis rather than myopic CNV. We planned an intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection but the patient noticed a sudden reduction of the visual acuity a few days before the anti-VEGF injection. The left fundus showed a MHRD due to the subretinal hemorrhage. Five days later, the SS-OCT images confirmed a recession of the CNV and a resolution of the MHRD. Conclusions Rapid and spontaneous resolution of both myopic CNV and hemorrhagic MHRD suggest that there may have been a mutual mechanism causing the MHRD and CNV. A careful follow-up before doing surgery may be a choice for hemorrhagic MHRD in eyes with pathologic myopia.

At present, the world is at the tipping point of the outbreak of mpox. The World Health Organization has declared the current mpox outbreak a ‘public health emergency of international concern’. Mpox has been shown to be associated with several ocular manifestations. Given the current state of the mpox outbreak, healthcare providers, particularly ophthalmologists, need to be aware of these ophthalmic symptoms and how to manage them. In this review, we highlight current knowledge on the ocular symptoms of mpox virus (MPXV) infections and how to detect them. In addition, we summarize the treatment strategies for these ocular manifestations of MPXV infections and outline the relationship between vaccination and the ocular symptoms of mpox.

Uveitis is one of the most common ocular complications in people living with the Human immunodeficiency virus (HIV) and can be classified into HIV-induced uveitis, co-infection related uveitis, immune recovery uveitis, and drug-induced uveitis. The introduction of antiretroviral therapy has considerably changed the incidence, diagnosis, and treatment of different types of HIV-related uveitis. Furthermore, the specific immune condition of patients infected with HIV makes diagnosing HIV-related uveitis difficult. Recent studies have focused on the growing prevalence of syphilis/tuberculosis co-infection in uveitis. Simultaneously, more studies have demonstrated that HIV can directly contribute to the incidence of uveitis. However, the detailed mechanism has not been studied. Immune recovery uveitis is diagnosed by exclusion, and recent studies have addressed the role of biomarkers in its diagnosis. This review highlights recent updates on HIV-related uveitis. Furthermore, it aims to draw the attention of infectious disease physicians and ophthalmologists to the ocular health of patients infected with HIV.

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner–Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

Abstract Background To report 2 cases of bilateral granulomatous panuveitis accompanied by chronic active Epstein-Barr virus infection (CAEBV). Case presentation Case 1 was a 38-year-old man who had a history of bilateral mild panuveitis who was diagnosed with CAEBV. Fifteen months later, a severe bilateral granulomatous panuveitis developed. White infiltrates covered the optic disc and all the retinal vessels of the right eye, and white nodules were seen along the retinal veins and arteries of the left eye. Case 2 was a 34-year-old man with bilateral panuveitis showing mutton-fat keratic precipitates and diffuse vitreous opacity in both eyes. A snow ball-like vitreous opacity was present in the right eye. Systemic investigations revealed the presence of CAEBV. In both cases, a comprehensive polymerase chain reaction (PCR) analyses of the aqueous humor detected significant copy numbers of EBV-DNA. The intraocular inflammation did not respond to steroid, methotrexate, and other immunosuppressive therapies, but was ameliorated after hematopoietic stem cell transplantation with preceding chemotherapy and low-dose total body irradiation in both cases. Conclusion Granulomatous panuveitis can develop in eyes with CAEBV as a primary symptom. Ophthalmologists should rule out CAEBV when EBV-DNA is positive in the intraocular fluids of steroid-resistant panuveitis.

Advancement of imaging technology in retinal diseases provides us more precise understanding and new insights into the diseases’ pathologies. Diabetic retinopathy (DR) is one of the leading causes of sight-threatening retinal diseases worldwide. Colour fundus photography and fluorescein angiography have long been golden standard methods in detecting retinal vascular pathology in this disease. One of the major advancements is macular observation given by optical coherence tomography (OCT). OCT dramatically improves the diagnostic quality in macular edema in DR. The technology of OCT is also applied to angiography (OCT angiograph: OCTA), which enables retinal vascular imaging without venous dye injection. Similar to OCTA, in terms of their low invasiveness, single blue color SLO image could be an alternative method in detecting non-perfused areas. Conventional optical photography has been gradually replaced to scanning laser ophthalmoscopy (SLO), which also make it possible to produce spectacular ultra-widefield (UWF) images. Since retinal vascular changes of DR are found in the whole retina up to periphery, it would be one of the best targets in UWF imaging. Additionally, evolvement of artificial intelligence (AI) has been applied to automated diagnosis of DR, and AI-based DR management is one of the major topics in this field. This review is trying to look back on the progress of imaging of DR comprehensively from the past to the present.

Summary: Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability. Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China. Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959–0·977) or higher for myopic macular degeneration and 0·913 (0·906–0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957–0·994] for myopic macular degeneration and 0·973 [0·941–0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries. Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine. Funding: None.

Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro. We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment.

Myopia is a global health issue, and the prevalence of high myopia has increased significantly in the past five to six decades. The high incidence of myopia and its vision-threatening course emphasize the need for automated methods to screen for high myopia and its serious form, named pathologic myopia (PM). Artificial intelligence (AI)-based applications have been extensively applied in medicine, and these applications have focused on analyzing ophthalmic images to diagnose the disease and to determine prognosis from these images. However, unlike diseases that mainly show pathologic changes in the fundus, high myopia and PM generate even more data because both the ophthalmic information and morphological changes in the retina and choroid need to be analyzed. In this review, we present how AI techniques have been used to diagnose and manage high myopia, PM, and other ocular diseases and discuss the current capacity of AI in assisting in preventing high myopia.

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves’ disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.

Purpose: Vasoproliferative tumors (VPTs) are rare benign tumors, and detailed indocyanine green angiographic (ICGA) findings in eyes with VPTs have not been reported. We present the characteristic ICGA findings in seven eyes with a VPT. Observations: We present the fluorescein angiographic (FA) and ICGA findings of seven consecutive patients who were diagnosed with primary VPT from April 2013 to March 2015 in the Oncology Service of the Department of Ophthalmology, Tokyo Medical and Dental University. We reviewed the demographics of the seven patients with VPTs. Abnormal vessels within the tumor were observed in three cases with active tumors. These vessels were hypofluorescent in the ICGA images in the scar phase. On the other hand, three cases in which the exudation remained from the initial visit to the last examination had abnormal vessels in the ICGA images. The remaining case had one straight vessel in the tumor from the initial to the last examination in the scar phase. FA in the active phase changed from hyperfluorescent leakage to staining in one eye, and the remaining six eyes continued to show hyperfluorescent leakage throughout the examination period. Conclusions: The leakage of fluorescein continued from the initial to the final examination even after the activity of the tumor had decreased. In the active phase, ICGA showed abnormal vessels with or without leakage, and the tumors at the scar phase show a hypofluorescent lesion. Importance: ICGA supported the ophthalmoscopic findings, and can be used as a diagnostic aid to confirm a regression of the VPTs.

Purpose: To report the findings determined by multimodal imaging in an eye with secondary vitreoretinal lymphoma (VRL) with optic neuritis and retinal vasculitis. Observation: The case was a 71-year-old woman with a secondary VRL exhibiting optic neuritis and retinal vasculitis in her right eye. Color fundus photographs and fluorescein angiograms showed optic neuritis and vasculitis in the posterior pole of the right eye. Indocyanine green angiography showed dye staining of the retinal vein walls in the late phase. Fundus autofluorescence showed fuzzy hyper-autofluorescence surrounded by mottled hyper-and hypo-autofluorescence in the right eye. OCT showed a retina with uniform infiltration and a thickened retinal pigmented epithelium (RPE) layer, perforated RPE, small RPE detachments, and hyperrefrective or isorefrective masses on the degenerated RPE layer in the marginal area. Her left eye showed a degenerated RPE and oval shaped iso-reflective lesions on the RPE. Conclusion: The findings indicate that it is important to examine the marginal areas of eyes clinically diagnosed with VRL accompanied by optic neuritis and retinal vasculitis by multimodal imaging because these images can show the inflammatory signs of typical VRL including the sub-RPE lesions.

The retinal pigment epithelium (RPE) is essential for maintaining retinal homeostasis by removing and recycling photoreceptor outer segment (POS) in membranes. It also produces and secretes growth factors involved in retinal homeostasis. Arrestin 1 (ARR1) is specifically expressed in photoreceptors (PRs) and a vital molecule for keeping visual cycle between PRs and RPE. In the present study, we showed the expression of ARR1 was decreased by form-deprivation (FD) in retina of rat. The ARR1 was detected in the RPE of the controls but not in the RPE of FD, which indicates RPE phagocytes POS containing ARR1. Furthermore, we overexpressed ARR1 in cultured human RPE and revealed the ARR1 upregulates bFGF expression and downregulates TGF-β1, -β2 and bone morphogenetic protein-2 (BMP-2). The upregulation of bFGF by ARR1 directly works for PR survival and the downregulation of TGF-βs by ARR1 inhibits epithelial mesenchymal transition (EMT) of RPE, which is the underlying mechanism of keeping retinal homeostasis. Our results also indicate the regulation of ARR1 expression in RPE might become a novel therapeutic option for various ocular diseases. Keywords: Arrestin1, Retinal homeostasis, Retinal pigment epithelium, Photoreceptor, Transforming growth factor beta, Basic fibroblast growth factor

Myopic maculopathy is a complication of myopia that often progresses to blindness. Here, in a genome-wide association study, Hosoda et al. find that rs11873439 intronic to CCDC102B is associated with myopic maculopathy, but not with myopia, thus representing a risk factor independent of myopia.

Purpose: To report the swept-source optical coherence tomographic (OCT) findings in two eyes with choroidal metastases. Observations: Two patients with choroidal metastasis were studied. The metastasis was from a breast cancer in Case 1 and from a lung cancer in Case 2. In Case 1, swept-source OCT showed a highly reflective solid tumor with low optical reflective tissues that had replaced the choroidal tissue. Swept-source OCT was able to image the choroidal mass where other fundus imaging methods such as fluorescein angiography did not show the mass. Ophthalmoscopy of Case 2 showed hemorrhages in the inner retina, on the tumor, and in the vitreous. Swept-source OCT showed a subretinal mass with a steeple-crowned cap and a ruptured Bruch's membrane on the tumor. Conclusion and importance: Swept-source OCT imaging can detect the inner structure of a choroidal mass and retina around it in good detail.

Abstract Background To report a case of Suprachoroidal Hemorrhage followed by Swept-Source Optical Coherence Tomography. Case presentation A 66-year-old woman with a rhegmatogenous retinal detachment in her left eye underwent pars plana vitrectomy. During the intraocular photocoagulation for a retinal tear after fluid-air exchange, a vitreous hemorrhage and suprachoroidal hemorrhage (SCH) developed. The surgical incisions were closed after filling the vitreous cavity with silicone oil. Two weeks later, the hemolyzed hemorrhage was removed, and new silicone oil was injected. After the surgery, a low reflective region was detected near the macula in the swept-source optical coherence tomographic (SS-OCT) images. The low reflective region was caused by the residual hemorrhage. The size of the reflective region gradually decreased and was not present at 3 months. We conclude that SS-OCT can be used to follow the resolution of a suprachoroidal hemorrhage. Conclusion SS-OCT can be used to detect and follow the natural course of a suprachoroidal hemorrhage including the absorptive processes.

Use of biologics has been widely advocated for inflammatory diseases recently. Anti-tumor necrosis factor (TNF)-α antibody therapy is reportedly effective against ocular inflammation. However, side effects of TNF-α inhibition have been reported, particularly in the form of exacerbation of infections such as tuberculosis. Paradoxical reactions such as exacerbated inflammation are also well known. Around 20 million humans are infected with human T-cell leukemia virus type 1 (HTLV-1) globally, and this virus can cause adult T-cell leukemia, HTLV-1-associated myelopathy and HTLV-1 uveitis. As for ophthalmic concerns, it has not been identified whether anti-TNF-α antibody stimulates HTLV-1-infected cells and ocular cells to induce HTLV-1 uveitis in HTLV-1 carriers. Here we investigated the effects of anti-TNF-α antibody on ocular status under HTLV-1 infectious conditions using ocular cells and HTLV-1-infected cells in vitro. We used the ARPE-19 human retinal pigment epithelial cell line as ocular cells considered to play an important role in the blood-ocular barrier, and the MT2 HTLV-1-infected cell line. Jurkat cells were used as controls. Infliximab (IFX) was used as an anti-TNF-α antibody to achieve TNF-α inhibition. We evaluated the production of inflammatory cytokines and intercellular adhesion molecule (ICAM)-1, proliferation of ARPE-19, expression of TNF-α receptor (TNF-R) and HTLV-1 proviral DNA, and the percentage of apoptotic ARPE-19. Inflammatory cytokines such as interleukin (IL)-6, IL-8, TNF, and ICAM-1 were significantly elevated through contact between ARPE-19 and MT2. Treatment with IFX tented to inhibit TNF production, although the level of production was low, but changes in IL-6, IL-8, and ICAM-1 remained unaffected. Expression of TNFR was unaltered by IFX treatment. HTLV-1 proviral DNA was not significantly changed with treatment. No change in cell growth rate or apoptotic rate of ARPE-19 was seen with the addition of IFX. In conclusion, IFX did not exacerbate production of inflammatory cytokines, and did not affect expression of TNFR, proliferation of ARPE-19, HTLV-1 proviral load, or apoptosis of ARPE-19. These results suggest that IFX does not exacerbate HTLV-1-related inflammation in the eye and represents an acceptable treatment option under HTLV-1 infectious conditions.

[This corrects the article DOI: 10.1371/journal.pone.0220143.].

PurposeTo evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM).MethodsA candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM).ResultsIn the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance.ConclusionsOf the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

PurposeTo determine the early signs of posterior staphylomas in highly myopic eyes of younger subjects by swept-source ultra-widefield optical coherence tomography (WF-OCT).MethodsThis was an observational case series study. Highly myopic subjects younger than 20 years old who were examined consecutively by prototype WF-OCT were studied. High myopia was defined according to the Ministry of Health and Welfare, Japan classification. A posterior displacement of the sclera and two OCT features indicating the staphyloma edges were used as markers of a staphyloma.ResultsFifty-five eyes of 30 patients with the mean age of 12.3 years, and the mean axial length of 27.9 mm were studied. Seven of the 55 eyes (12.7%) had a posterior displacement of the sclera and were diagnosed as having a staphyloma. Among the two OCT features of the staphyloma edges, a gradual thinning of the choroid toward the staphyloma edge and gradual re-thickening of choroid from the staphyloma edge toward the posterior pole were found in these 7 eyes. However, the other feature of an inward protrusion of the sclera at the staphyloma edge, was obvious in only 2 eyes. The subfoveal choroid and choroid nasal to the optic disc were significantly thinner in eyes with a staphyloma than those without it.ConclusionsThe changes of the choroidal thickness toward the staphyloma edge with the posterior displacement of the sclera were considered an early sign which precedes an inward protrusion of sclera at the staphyloma edge.

Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive T-cell malignancy with a high mortality rate, resulting in a lack of information among ophthalmologists. Here, we investigated the state of ophthalmic medical care for ATL and ATL-related ocular manifestations by conducting the first large-scale nationwide survey in Japan. A total of 115 facilities were surveyed, including all university hospitals in Japan that were members of the Japanese Ophthalmological Society and regional core facilities that were members of the Japanese Ocular Inflammation Society. The collected nationwide data on the state of medical care for ATL-related ocular manifestations and ATL-associated ocular findings were categorized, tallied, and analyzed. Of the 115 facilities, 69 (60%) responded. Overall, 28 facilities (43.0%) had experience in providing ophthalmic care to ATL patients. ATL-related ocular manifestations were most commonly diagnosed “based on blood tests and characteristic ophthalmic findings.” By analyzing the 48 reported cases of ATL-related ocular manifestations, common ATL-related ocular lesions were intraocular infiltration (22 cases, 45.8%) and opportunistic infections (19 cases, 39.6%). All cases of opportunistic infection were cytomegalovirus retinitis. Dry eye (3 cases, 6.3%), scleritis (2 cases, 4.2%), uveitis (1 case, 2.1%), and anemic retinopathy (1 case, 2.1%) were also seen. In conclusion, intraocular infiltration and cytomegalovirus retinitis are common among ATL patients, and ophthalmologists should keep these findings in mind in their practice.

PURPOSE:To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. METHODS:The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. RESULTS:The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13-89 years) and mean axial length of 29.5±2.2 mm (range:23.2-35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of

To examine an association between macular Bruch's membrane defects (MBMD) and a dome-shaped appearance of the macula (DSM).Retrospective, observational case series study.The study included highly myopic individuals who were consecutively examined between May 2014 and December 2015. The patients underwent swept-source optical coherence tomography (OCT) for visualization of DSM and MBMDs defined as Bruch´s membrane defects located at a distance of maximal 1500 μm from the foveola.Out of 1983 highly myopic eyes (1057 patients), 166 eyes (8.4%; 95% confidence interval (CI):7.2%,9.6%)) showed a DSM and 534 eyes showed a MBMD. In multivariate binary regression analysis, higher prevalence of DSM was associated with a higher prevalence of a MBMD (P