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Abstract Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.

Introduction: Osteopetrosis is a rare heritable disorder characterized by increased bone density resulting from osteoclast dysfunction. Major complications include bone fracture, osteomyelitis, anemia, and cranial nerve compression. Optic atrophy can occur due to compression of the optic nerve. Although osteomyelitis of the jaw is a common complication, it rarely occurs in the maxilla. Here, we report a case of a 74-year-old female with osteopetrosis who developed maxillary osteomyelitis, leading to orbital inflammation. Case Presentation: She was referred to our clinic for 2 months of ptosis and swelling of the left eyelid and temporal region. Previous imaging revealed a left intraorbital occupying lesion, but a biopsy of the temporal subcutaneous tissue did not provide a definitive diagnosis. After 7 months, she presented with severe temporal swelling and purulent discharge. Upon examination, maxillary osteomyelitis resulting from caries of the upper jaw was observed. Treatment with oral antibiotics, drainage of the temporal skin fistula, and regular cleaning of the maxillary drainage improved her symptoms. Conclusion: This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.

Purpose: The aim of this study was to examine the effects of foveal thickness (FT) fluctuation (FTF) on 2-year visual and morphological outcomes of eyes with central retinal vein occlusion (CRVO) undergoing anti-VEGF treatment for recurrent macular edema (ME) based on a pro re nata regimen. Design: Retrospective, observational case series. Participants: We analyzed 141 treatment-naive patients (141 eyes) with CRVO-ME at a multicenter retinal practice. Methods: We assessed FT using OCT at each study visit. Patients were divided into groups 0, 1, 2, and 3 according to increasing FTF. Main Outcome Measures: We evaluated the logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA), the length of the foveal ellipsoid zone (EZ) band defect measured using OCT, and the association of FTF with VA and EZ band defect length. Results: The mean baseline logMAR BCVA and FT were 0.65 ± 0.52 (Snellen equivalent range: 20/20–20/2000) and 661.1 ± 257.4 μm, respectively. The mean number of anti-VEGF injections administered was 5.6 ± 3.6. At the final examination, the mean logMAR BCVA and FT values were significantly improved relative to the baseline values (both P

Abstract A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P

Abstract Laser therapy is the most effective treatment considered for retinopathy of prematurity (ROP). We compared the foveal morphology of the retina in eyes with a history of ROP to that of full-term children. This cross-sectional comparative study included 74 patients with a history of ROP, aged 4–6 years. Among them, 41 underwent laser treatment for ROP. The clinical findings and retinal morphology in these patients were compared to that of 33 patients who had spontaneous ROP regression and 30 age-matched full-term controls. All the patients with ROP had 20/40 or better best-corrected visual acuity (BCVA). The foveal thickness was significantly thicker in laser-treated ROP eyes than in regressed ROP eyes and controls. The outer nuclear layer was significantly thicker, and the inner segment (IS) of the photoreceptors and the inner retinal layer were significantly thicker in the laser-treated ROP eyes than that in the control eyes. In the patients with ROP and controls, better BCVA was associated positively with deeper foveal depression, which was associated with a later gestational age. Our results suggest that prematurity and laser treatment affect the foveal morphology and BCVA.

ABSTRACT Aims/Introduction In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. Materials and Methods This is a real‐world clinical study including 1,552 patients with treatment‐naïve center‐involved DME. The patients were categorized into 4 categories by age at baseline (C1,

ABSTRACT Aims/Introduction Inhibition of peroxisome proliferator‐activated receptor gamma (PPARγ) phosphorylation mediated by cyclin‐dependent kinase 5 (Cdk5) is one of the main mechanisms of action of antidiabetic drugs. In this study, we analyzed the ocular expression and activation of Cdk5 in patients with proliferative diabetic retinopathy (PDR). Materials and Methods The concentrations of PPARγ, Cdk5 and its activating subunit (p35) were determined in the vitreous body of 24 PDR and 63 control eyes by enzyme‐linked immunosorbent assay. In addition, the messenger ribonucleic acid and protein expression levels of PPARγ, Cdk5 and p35 were measured in proliferative neovascular membranes from seven PDR eyes and non‐neovascular epiretinal membranes from five control eyes by quantitative real‐time polymerase chain reaction and immunohistochemical analysis. Results PPARγ, Cdk5 and p35 concentrations in the vitreous body were significantly higher in the PDR group compared with the control group. There was also a positive significant correlation of Cdk5 with PPARγ and p35 in the PDR group. Furthermore, the messenger ribonucleic acid expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes were significantly higher in the PDR group compared with the control group. Immunostaining showed increased protein expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes in the PDR group compared with the control group. Conclusions Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5‐mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR.

In this article, we report two patients who experienced the first onset of branch retinal vein occlusion (BRVO) 3 days after the administration of the BNT162b2 (Pfizer–BioNTech) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Case 1: A 50-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 2: A 56-year-old woman without any history of retinal disease developed vision loss in her right eye 3 days after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Case 1: Temporal superior BRVO and secondary macular edema (ME) were observed in the patient's right eye. Her best-corrected visual acuity (BCVA) was 20/25. Case 2: Temporal inferior BRVO and secondary ME were observed in the patient's right eye. Her BCVA was 13/20. Case 1: Three doses of intravitreal ranibizumab (IVR) were administered. Case 2: Three doses of IVR were administered. Case 1: ME resolved and BCVA improved to 20/20. Case 2: ME resolved and BCVA improved to 20/20. Both the cases showed a possible association between the SARS-CoV-2 vaccination and the first onset of BRVO.

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Objective We report the 2-year visual and psychological outcomes of the MERCURY study, examining the long-term effectiveness and safety of ranibizumab and subsequent therapy in Japanese patients with diabetic macular oedema with impaired visual acuity (VA) in the real-world setting.Methods and analysis This was a 24-month, phase 4, open-label, single-arm, multicentre, prospective, observational study. Following an initial dose of ranibizumab (0.5 mg) by intravitreal injection (0.05 mL), treatment was administered as needed after month 1. The primary treated eye (PTE) was the first eye that received a ranibizumab injection.Results In total, 209 patients were enrolled; 192 (91.9%) and 174 (83.3%) completed months 12 and 24, respectively. In the PTE set, mean±SD changes in best-corrected VA (BCVA) from baseline to months 12 (primary endpoint) and 24 were −0.08±0.35 (p=0.015) and −0.13±0.30 (p

Abstract The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P

Abstract Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.

PurposeTo investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).DesignA retrospective, observational case series.MethodsSetting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD.ResultsThirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group.ConclusionsThe recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.

PurposeTo evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM).MethodsThis retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed.ResultsMajor causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all PConclusionsThe characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

Retinal vascular occlusion after ocular surgery is a rare but serious complication. A history of cardiovascular diseases, retrobulbar anesthesia injection, high intraocular pressure during the perioperative period, and drug toxicity have been reported as possible causative factors. We report here two cases of multiple retinal vascular occlusions after the subconjunctival injection of gentamicin at the end of uncomplicated 25-gauge vitrectomy. Case 1 was a 61-year-old man who developed a macular hole in the right eye. Phacovitrectomy with gas tamponade was performed. On postoperative day (POD) 1, dot hemorrhage was observed on the temporal side of the optic disk. On POD10, macular whitening, retinal hemorrhage, and multiple occlusion of retinal arteries and veins were observed. Case 2 was a 51-year-old woman who was diagnosed with rhegmatogenous retinal detachment in the right eye and underwent phacovitrectomy with gas tamponade. On POD3, macular whitening with cotton wool spots and retinal hemorrhage were observed with macular ischemia owing to occlusion of retinal arteries and veins. In both cases, subconjunctival injection of gentamicin given at the end of surgery was the most suspected cause of retinal vascular occlusion.

Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.

Abstract Aims/Introduction To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. Materials and Methods This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. Results The results showed that 81.2% preferred intravitreal injections of anti‐VEGF antibodies as the first‐line therapy. The most important indicators for beginning anti‐VEGF therapy were: the best‐corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti‐VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub‐Tenon steroid injection were preferred. The contraindications for anti‐VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti‐VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. Conclusions Our results present the current clinical preferences of anti‐VEGF treatment for DME in Japan. The best‐corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti‐VEGF treatment as first‐line therapy and prefer the 1 + pro re nata regimen.

AIM: To investigate and compare the efficacy of two machine-learning technologies with deep-learning (DL) and support vector machine (SVM) for the detection of branch retinal vein occlusion (BRVO) using ultrawide-field fundus images. METHODS: This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated to compare the diagnostic abilities of the DL and SVM models. RESULTS: For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0% (95%CI: 93.8%-98.8%), 97.0% (95%CI: 89.7%-96.4%), 96.5% (95%CI: 94.3%-98.7%), 93.2% (95%CI: 90.5%-96.0%) and 0.976 (95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5% (95%CI: 77.8%-87.9%), 84.3% (95%CI: 75.8%-86.1%), 83.5% (95%CI: 78.4%-88.6%), 75.2% (95%CI: 72.1%-78.3%) and 0.857 (95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters (P

Purpose. The present study aimed to compare the accuracy of diabetic retinopathy (DR) staging with a deep convolutional neural network (DCNN) using two different types of fundus cameras and composite images. Method. The study included 491 ultra-wide-field fundus ophthalmoscopy and optical coherence tomography angiography (OCTA) images that passed an image-quality review and were graded as no apparent DR (NDR; 169 images), mild nonproliferative DR (NPDR; 76 images), moderate NPDR (54 images), severe NPDR (90 images), and proliferative DR (PDR; 102 images) by three retinal experts by the International Clinical Diabetic Retinopathy Severity Scale. The findings of tests 1 and 2 to identify no apparent diabetic retinopathy (NDR) and PDR, respectively, were then assessed. For each verification, Optos, OCTA, and Optos OCTA imaging scans with DCNN were performed. Result. The Optos, OCTA, and Optos OCTA imaging test results for comparison between NDR and DR showed mean areas under the curve (AUC) of 0.79, 0.883, and 0.847; sensitivity rates of 80.9%, 83.9%, and 78.6%; and specificity rates of 55%, 71.6%, and 69.8%, respectively. Meanwhile, the Optos, OCTA, and Optos OCTA imaging test results for comparison between NDR and PDR showed mean AUC of 0.981, 0.928, and 0.964; sensitivity rates of 90.2%, 74.5%, and 80.4%; and specificity rates of 97%, 97%, and 96.4%, respectively. Conclusion. The combination of Optos and OCTA imaging with DCNN could detect DR at desirable levels of accuracy and may be useful in clinical practice and retinal screening. Although the combination of multiple imaging techniques might overcome their individual weaknesses and provide comprehensive imaging, artificial intelligence in classifying multimodal images has not always produced accurate results.

This study examined and compared outcomes of deep learning (DL) in identifying swept-source optical coherence tomography (OCT) images without myopic macular lesions [i.e., no high myopia (nHM) vs. high myopia (HM)], and OCT images with myopic macular lesions [e.g., myopic choroidal neovascularization (mCNV) and retinoschisis (RS)]. A total of 910 SS-OCT images were included in the study as follows and analyzed by k-fold cross-validation (k = 5) using DL's renowned model, Visual Geometry Group-16: nHM, 146 images; HM, 531 images; mCNV, 122 images; and RS, 111 images (n = 910). The binary classification of OCT images with or without myopic macular lesions; the binary classification of HM images and images with myopic macular lesions (i.e., mCNV and RS images); and the ternary classification of HM, mCNV, and RS images were examined. Additionally, sensitivity, specificity, and the area under the curve (AUC) for the binary classifications as well as the correct answer rate for ternary classification were examined. The classification results of OCT images with or without myopic macular lesions were as follows: AUC, 0.970; sensitivity, 90.6%; specificity, 94.2%. The classification results of HM images and images with myopic macular lesions were as follows: AUC, 1.000; sensitivity, 100.0%; specificity, 100.0%. The correct answer rate in the ternary classification of HM images, mCNV images, and RS images were as follows: HM images, 96.5%; mCNV images, 77.9%; and RS, 67.6% with mean, 88.9%.Using noninvasive, easy-to-obtain swept-source OCT images, the DL model was able to classify OCT images without myopic macular lesions and OCT images with myopic macular lesions such as mCNV and RS with high accuracy. The study results suggest the possibility of conducting highly accurate screening of ocular diseases using artificial intelligence, which may improve the prevention of blindness and reduce workloads for ophthalmologists.

The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA.

AIM: To investigate the changes in the choroidal thickness in healthy pediatric children in a longitudinal study, and to determine the ocular and systemic parameters that were significantly correlated with the changes in the choroidal thickness. METHODS: This study included 64 eyes of 34 healthy Japanese children with a mean age (±SD) of 4.4 (±0.4)y (range, 3.6-5.8y) at baseline. Swept-source optical coherence tomography (SS-OCT) was used to record images of the retina and choroid at the baseline and after a mean follow-up period of about 1.5y. The 3D raster scan protocol was used to construct the choroidal thickness map. Mean choroidal thickness was calculated for each of the nine sectors of the Early Treatment Diabetic Retinopathy Study grid. Best-corrected visual acuity, axial length, body height, and weight were also measured. Changes in measurements were defined as the baseline values subtracted from the values at the final visit. A generalized estimating equation was used to eliminate the effect of within-subject intereye correlations. RESULTS: The mean central choroidal thickness was significantly reduced during the follow-up period (baseline, 301.8±8.6 µm; final visit, 286.6±8.0 µm, P

Purpose: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. Methods: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients’ baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. Results: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = −0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = −0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. Conclusions: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results.

Evaluating the discrimination ability of a deep convolution neural network for ultrawide-field pseudocolor imaging and ultrawide-field autofluorescence of retinitis pigmentosa. In total, the 373 ultrawide-field pseudocolor and ultrawide-field autofluorescence images (150, retinitis pigmentosa; 223, normal) obtained from the patients who visited the Department of Ophthalmology, Tsukazaki Hospital were used. Training with a convolutional neural network on these learning data objects was conducted. We examined the K-fold cross validation (K = 5). The mean area under the curve of the ultrawide-field pseudocolor group was 0.998 (95% confidence interval (CI) [0.9953–1.0]) and that of the ultrawide-field autofluorescence group was 1.0 (95% CI [0.9994–1.0]). The sensitivity and specificity of the ultrawide-field pseudocolor group were 99.3% (95% CI [96.3%–100.0%]) and 99.1% (95% CI [96.1%–99.7%]), and those of the ultrawide-field autofluorescence group were 100% (95% CI [97.6%–100%]) and 99.5% (95% CI [96.8%–99.9%]), respectively. Heatmaps were in accordance with the clinician’s observations. Using the proposed deep neural network model, retinitis pigmentosa can be distinguished from healthy eyes with high sensitivity and specificity on ultrawide-field pseudocolor and ultrawide-field autofluorescence images.

We investigated the rates of the use of steroids in Japanese central serous chorioretinopathy (CSC) cases and differences in the characteristics of CSC with and without steroids. A total of 538 eyes of 477 patients diagnosed with CSC, with 3 months or more of follow-up between April 2013 and June 2017 at 8 institutions. Patients with CSC with more than 3 months of follow-up were identified by OCT and fluorescein angiography at 8 institutions. Data collected included patient demographics, history of corticosteroid medication and smoking, spherical errors, findings of angiography, subfoveal choroidal thickness, and changes through the follow-up period. Differences in these findings were analyzed in cases with and without corticosteroid treatment. Among the 477 patients (344 men,133 women), 74 (15.5%) (39 men, 35 women) underwent current or prior steroid treatment. Cases with steroids were higher age (p = 0.0403) and showed no male prevalence, more bilateral involvement (p < 0.0001), and the affected eyes had multiple pigment epithelial detachment (p

We aimed to assess the ability of deep learning (DL) and support vector machine (SVM) to detect a nonperfusion area (NPA) caused by retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA) images. The study included 322 OCTA images (normal: 148; NPA owing to RVO: 174 [128 branch RVO images and 46 central RVO images]). Training to construct the DL model using deep convolutional neural network (DNN) algorithms was provided using OCTA images. The SVM used a scikit-learn library with a radial basis function kernel. The area under the curve (AUC), sensitivity and specificity for detecting an NPA were examined. We compared the diagnostic ability (sensitivity, specificity and average required time) between the DNN, SVM and seven ophthalmologists. Heat maps were generated. With regard to the DNN, the mean AUC, sensitivity, specificity and average required time for distinguishing RVO OCTA images with an NPA from normal OCTA images were 0.986, 93.7%, 97.3% and 176.9 s, respectively. With regard to SVM, the mean AUC, sensitivity, and specificity were 0.880, 79.3%, and 81.1%, respectively. With regard to the seven ophthalmologists, the mean AUC, sensitivity, specificity and average required time were 0.962, 90.8%, 89.2%, and 700.6 s, respectively. The DNN focused on the foveal avascular zone and NPA in heat maps. The performance of the DNN was significantly better than that of SVM in all parameters (p < 0.01, all) and that of the ophthalmologists in AUC and specificity (p < 0.01, all). The combination of DL and OCTA images had high accuracy for the detection of an NPA, and it might be useful in clinical practice and retinal screening.

PURPOSE:To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). METHODS:This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. RESULTS:IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. CONCLUSION:Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis.

We aimed to investigate the detection of idiopathic macular holes (MHs) using ultra-wide-field fundus images (Optos) with deep learning, which is a machine learning technology. The study included 910 Optos color images (715 normal images, 195 MH images). Of these 910 images, 637 were learning images (501 normal images, 136 MH images) and 273 were test images (214 normal images and 59 MH images). We conducted training with a deep convolutional neural network (CNN) using the images and constructed a deep-learning model. The CNN exhibited high sensitivity of 100% (95% confidence interval CI [93.5–100%]) and high specificity of 99.5% (95% CI [97.1–99.9%]). The area under the curve was 0.9993 (95% CI [0.9993–0.9994]). Our findings suggest that MHs could be diagnosed using an approach involving wide angle camera images and deep learning.

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment.

The aim of this study is to assess the performance of two machine-learning technologies, namely, deep learning (DL) and support vector machine (SVM) algorithms, for detecting central retinal vein occlusion (CRVO) in ultrawide-field fundus images. Images from 125 CRVO patients (n=125 images) and 202 non-CRVO normal subjects (n=238 images) were included in this study. Training to construct the DL model using deep convolutional neural network algorithms was provided using ultrawide-field fundus images. The SVM uses scikit-learn library with a radial basis function kernel. The diagnostic abilities of DL and the SVM were compared by assessing their sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve for CRVO. For diagnosing CRVO, the DL model had a sensitivity of 98.4% (95% confidence interval (CI), 94.3–99.8%) and a specificity of 97.9% (95% CI, 94.6–99.1%) with an AUC of 0.989 (95% CI, 0.980–0.999). In contrast, the SVM model had a sensitivity of 84.0% (95% CI, 76.3–89.3%) and a specificity of 87.5% (95% CI, 82.7–91.1%) with an AUC of 0.895 (95% CI, 0.859–0.931). Thus, the DL model outperformed the SVM model in all indices assessed (P

The purpose of this study was to determine the effect of optical correction on the best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (CT) in the eyes of children with anisohypermetropic amblyopia. Twenty-four anisohypermetropic amblyopic eyes and their fellow eyes of 24 patients and twenty-three eyes of 23 age-matched control children were studied. After one year of optical correction, the BCVA in the anisohypermetropic amblyopic eyes was significantly improved. Before the treatment, the mean subfoveal CT in the amblyopic eyes was 351.9 ± 59.4 μm which was significantly thicker than that of control eyes at 302.4 ± 63.2 μm. After the treatment, the amount of change in the subfoveal CT in the amblyopic and fellow eyes was greater than that in the control eyes. The amblyopic and fellow eyes with thicker choroids had a greater thinning of the choroid whereas eyes with thinner choroids had a greater thickening of the choroid. We conclude that wearing corrective lenses improves the visual acuity, and induces changes of the subfoveal CT in eyes with anisohypermetropic amblyopia.

Purpose: To report the morphologic features of a choroidal osteoma using swept-source optical coherence tomography (SS-OCT) and fundus autofluorescence (FAF). Methods: Two eyes of two cases with a choroidal osteoma were studied using SS-OCT and FAF. Results: The location of the tumor was circumpapillary without macular involvement in case 1 and juxtapapillary with macular involvement in case 2. Both cases had a mixture of calcified and decalcified areas, and a concomitant choroidal neovascularization was found in case 2. The FAF images showed decreased autofluorescence in the central decalcified regions and relatively preserved fluorescence in marginal calcified regions in both cases. SS-OCT revealed a normal inner retina and an abnormal outer retina in both cases, and subretinal fluid in case 2. The calcified regions appeared sponge-like and were multilayered in case 2. A lamellar reflective pattern was observed in the decalcified regions in case 1, and hyperreflective mound-like areas were observed in both cases. SS-OCT demonstrated hyperreflective areas above Bruch's membrane accompanied by disruption of Bruch's membrane in case 1. The chorioscleral border was visible in both cases. Conclusions: The FAF pattern in the calcified and decalcified areas of the choroidal osteoma may correspond to the different stage of tumor evolution. The SS-OCT findings indicate that choroidal osteomas can have characteristic reflective patterns and alterations of the overlying retina.

Purpose: We report a case of methicillin-resistant Staphylococcus aureus (MRSA) keratitis after Descemet's stripping automated endothelial keratoplasty (DSAEK). Case Report: An 87-year-old woman who had undergone a DSAEK 4 months previously was referred to Tokushima University Hospital with a diagnosis of infectious keratitis after DSAEK. A white abscess and infiltration in the inferior cornea of the right eye were observed. We started an empiric therapy using topical levofloxacin and chloramphenicol on the basis of the microscopic findings of the corneal scraping concurrently with cultivation of the cornea. Results: A strain of MRSA was isolated from the corneal sample. Although the strain was susceptible to chloramphenicol, it was resistant to quinolone. The keratitis improved rapidly due to empiric therapy, and topical steroids could be resumed 6 days after initiation of the empiric therapy. Conclusions: To our knowledge, this is the first case of MRSA keratitis, and the second case of bacterial keratitis, after DSAEK. MRSA keratitis can occur following uneventful DSAEK. The empiric therapy on the basis of results from a light microscopic examination of a Gram-stained corneal scraping and restarting topical steroids in the early stages of medication contributed to the good clinical course of this case.

To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT).A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas.In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P

To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes.This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images.The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise.Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area.

[This corrects the article DOI: 10.1371/journal.pone.0164672.].

PURPOSE:To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS:This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. RESULTS:The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P

To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC).This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT.The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively).The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels.

Purpose: To report a case of delayed-onset endophthalmitis after implantation of a preloaded intraocular lens (IOL) and examine the surgically removed IOL by scanning electron microscopy (SEM). Case: A 77-year-old female underwent uneventful phacoemulsification and aspiration with preloaded silicone IOL implantation. Since intraocular inflammation unexpectedly worsened 1 month after the surgery, she was referred to our hospital. Her visual acuity was hand motion in the left eye. Hypopyon and fibrin formation were observed in the anterior chamber. A diagnosis of postoperative delayed-onset endophthalmitis was made, and vitrectomy with anterior chamber wash-out was performed. As intraocular inflammation remained unchanged postoperatively, an additional surgery with IOL removal was performed. We cultivated the surgically removed samples of aqueous humor and vitreous fluid under both aerobic and anaerobic conditions, performed 16S rDNA clone library analysis of these clinical samples, and examined the removed IOL by SEM. Result: Inflammation subsided after the re-operation. Although cultures of aqueous and vitreous samples were negative, DNA of Propionibacterium acnes was detected in the aqueous humor. The SEM images showed that the rod bacteria and biofilm-like material formed on the tip of the IOL haptic. Conclusion: Delayed-onset endophthalmitis may occur after uneventful implantation of a preloaded IOL. The SEM findings suggested that the tip of the preloaded IOL haptic might scratch bacteria which adhered to the tip of the injector nozzle when the IOL was inserted into the anterior chamber. In some cases with delayed-onset endophthalmitis, IOL removal is needed to eliminate the bacteria which adhere to the tip of the IOL haptic.

Purpose: To report the clinical findings of 2 patients with focal choroidal excavation in the macula detected by spectral-domain optical coherence tomography (SD-OCT). Methods: Three eyes of 2 patients with a focal macular choroidal excavation detected by SD-OCT were studied. The eyes were examined by fundus autofluorescence (FAF), fluorescein angiography, fundus-related microperimetry, and multifocal electroretinography (mfERG). Results: In spite of a complaint of metamorphopsia, the visual acuity was normal in 2 eyes. SD-OCT demonstrated a choroidal excavation in the macula but the foveal contour was normal in 3 eyes. The excavation involved the outer retinal layers up to the external limiting membrane in all eyes, and a type 2 secondary choroidal neovascularization (CNV) developed in 1 of the 3 eyes. There were areas of hypoautofluorescence in the FAF images, and areas of decreased retinal sensitivity determined by microperimetry. These areas corresponded to the choroidal excavation in all eyes. The P1 amplitudes of the mfERGs were decreased in the fovea of 1 eye without a CNV. Conclusions: The choroidal excavation remained stable for 3 years in 2 eyes, a secondary CNV developed in 1 eye during the course of the disease. More cases and longer follow-up periods will be necessary to determine the etiology, clinical course, and visual prognosis of eyes with a choroidal excavation.

Toshiyuki Oshitari1, Noriko Asaumi1, Masaru Watanabe1, Ken Kumagai1, Yoshinori Mitamura1,21Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 2Department of Ophthalmology and Visual Science, Chuo-ku, Chiba, JapanAbstract: We report a case of severe diabetic macular edema (DME) that developed after pioglitazone was used by a patient with proliferative diabetic retinopathy. A 30-year-old woman with poorly controlled type 2 diabetes mellitus visited our clinic in 2004. She had moderate pre-proliferative diabetic retinopathy OU. Because of the rapid progression of the diabetic retinopathy, she received pan-retinal photocoagulation in both eyes. Two weeks before using pioglitazone, her visual acuity was 0.9 OD and 0.7 OS. On October 2007, pioglitazone was prescribed by her internist because of poorly controlled blood glucose level. Two weeks later, her body weight increased, and her face became edematous. Her visual acuity decreased to 0.5 OU, and ophthlamoscopy showed severe DME in both eyes. Two weeks after stopping pioglitazone, her visual acuity improved to 0.8 OD and 0.5 OS, but the DME was still severe in the optical coherence tomographic images. Then, one half the usual dose (25 mg) of spironolactone, a diuretic, was given and her macular edema was resolved. Her final visual acuity improved to 0.9 OD and 0.7 OS. We recommend that when a patient taking pioglitazone complains of decreased vision, the physician should promptly consult an ophthalmologist.Keywords: pioglitazone, diabetic macular edema, spironolactone, optical coherence tomography

Natsuyo Hata1, Toshiyuki Oshitari1,2, Akiko Yokoyama1,3, Yoshinori Mitamura1, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan; 2Department of Ophthalmology, Kimitsu Central Hospital, Kisarazu City, Chiba, Japan; 3Department of Ophthalmology, Inoue Memorial Hospital, Chuo-ku, Chiba, JapanAbstract: The purpose of this study was to determine whether the expression of ER stress-related factors IRE1α, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion injury. After 60 minutes of ischemia, the rat retinas were reperfused, and retinas were isolated and fixed after 6, 9, 12, 18, and 24 hours, and 2, 5, and 9 days of reperfusion. Cryosections were immunostained with Fluoro-Jade B, a degenerating neuron marker to label degenerating neurons. Semi-quantitative analysis of the expression of IRE1α, ASK1, SEK1, and JNK were performed in both control and ischemic retinas. In ischemic retinas, the intensities of IRE1α immunoreactivity in the ganglion cell layer (GCL) were significantly higher than in the control retinas. In ischemic retinas, the numbers of SEK1-, ASK1-, and JNK-positive cells were significantly increased in the GCL compared to those in the control retinas. In addition, the cells that were positive for SEK1-, ASK1-, and JNK were also positive for Fluoro-Jade B-positive cells. These results indicate that the increased expression of ER stress-related factors was, in part, associated with the retinal neuronal abnormalities after ischemia-reperfusion injury in rat retinas.Keywords: endoplasmic reticulum, IRE1α, apoptosis signal-regulating kinase 1, SAPK/ERK kinase 1, c-Jun N-terminal kinase, Fluoro-Jade B, ischemia-reperfusion injury

Purpose. To evaluate the movement of the anterior and posterior lens poles during naturally stimulated accommodation in children using anterior segment optical coherence tomography (OCT). Methods. This is a prospective, observational, noncomparative case series including 18 eyes of nine children. Analysis of the anterior segment in the accommodated and unaccommodated state (with cycloplegia) was done using anterior segment OCT. The main outcome measures were the position of the anterior and posterior lens poles (in relation to the cornea) and lens thickness (LT). Results. A Statistically significant forward movement of the anterior lens pole and backward movement of the posterior lens pole with an increase in LT were found during accommodation (P

We present a case of prepapillary vascular loops complicated by a suspected macroaneurysm rupture which was treated with intravitreal bevacizumab (IVB). A 62-year-old woman presented with decreased vision and myodesopsia in her left eye. Her best-corrected visual acuity (BCVA) was 0.6 in the left eye. Fundus examination disclosed an elevated, round, and reddish lesion, retinal hemorrhage at the superior aspect of the optic disc, retinal opacification along the superior branch retinal artery, and a small vitreous hemorrhage. Optical coherence tomography showed a serous retinal detachment, and indocyanine green angiography demonstrated prepapillary vascular loops and a hypofluorescent area with hyperfluorescent margins. These findings suggested the presence of a macroaneurysm. No filling of the dye in the aneurysm-like dilatation suggested a blockage of the lumen with a thrombus which might be associated with a branch retinal artery occlusion (BRAO). A diagnosis of prepapillary vascular loops complicated by a suspected macroaneurysm rupture and BRAO was made. Because of a persistent serous retinal detachment, IVB was performed. One month later, the BCVA improved to 1.0. Fundus examination disclosed an organized yellowish-white macroaneurysm and resolution of the serous retinal detachment. We recommend careful monitoring of patients with prepapillary vascular loops because of complications such as macroaneurysm rupture and BRAO.

Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown.Reb eyedrops were administered to the murine model of SS aged 4-8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment.Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces.

With recent development of spectral-domain optical coherence tomography (SD-OCT), the pathological changes of retina can be observed in much greater detail. SD-OCT clearly delineates three highly reflective lines in the outer retina, which are external limiting membrane (ELM), photoreceptor inner and outer segment (IS/OS) junction, and cone outer segment tips (COST) in order from inside. These lines can serve as hallmarks for the evaluation of photoreceptor condition. In retinitis pigmentosa (RP) leading to photoreceptor degeneration, the ELM, IS/OS, and COST lines are shortened with the progression of the disease. In addition, shortening of the ELM, IS/OS and COST lines is significantly associated with each other. The line length is longest in the ELM, followed by the IS/OS, and COST, suggesting that retinal layer becomes disorganized first at the COST, followed by the IS/OS and finally the ELM. This finding is consistent with the previous report that the earliest histopathological change in RP is a shortening of the photoreceptor outer segments. On the other hand, retinal layer becomes restored first at the ELM, followed by the IS/OS and finally the COST after macular hole surgery. There may be a directionality of photoreceptor impairment or restoration on optical coherence tomographic image.

BACKGROUND: Olig1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in Olig1(-/-) mice is significantly slower than wide-type (WT) mice (19.8 ± 2.2 in Olig1(-/-) mice and 9.5 ± 0.3 days in WT mice). In addition, 10% of Olig1(-/-) mice did not develop EAE by the end of the observation periods (60 days). The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/-) mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/-) mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/-) mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS.