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Ayumi Ota, Yoshiaki Tanaka, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro Kakehashi Department of Ophthalmology, Jichi Medical University, Saitama Medical Center, Omiya-ku, Saitama, Japan Purpose: To clarify the relationship between variations in posterior vitreous detachments (PVDs) and visual prognoses in idiopathic epiretinal membranes (ERMs).Methods: In this retrospective, observational, and consecutive case series, we observed variations in PVDs in 37 patients (mean age, 65.7±11.0 years) with ERMs and followed them for 2 years. Three PVD types were found biomicroscopically: no PVD, complete PVD with collapse (C-PVD with collapse), and partial PVD without shrinkage, with persistent vitreous attachment to the macula through the premacular hole of the posterior hyaloid membrane (P-PVD without shrinkage [M]). The best-corrected visual acuity (BCVA) was measured and converted to the logarithm of the minimum angle of resolution (logMAR) BCVA at the first visit and 2 years later.Results: No PVD was observed in 16 of the 37 eyes (mean age, 61.3±11.3 years), C-PVD with collapse in 11 of the 37 eyes (mean age, 69.1±9.9 years), and P-PVD without shrinkage (M) in 10 of the 37 eyes (mean age, 69.3±10.9 years). The logMAR BCVA at the first visit was the worst in the P-PVD without shrinkage (M) group (0.22±0.35) compared with the no-PVD group (−0.019±0.07; P

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

Purpose: To evaluate the diagnostic utility of serum prolactin (PRL) and lactate (LAC) concentrations for patients presenting with either or both convulsions and transient loss of consciousness (TLOC) in the emergency room (ER)., Methods: This was a retrospective single-center study conducted in a tertiary care hospital ER. Medical records of consecutive patients who presented with convulsions or TLOC between January 2018 and December 2020 were reviewed. Patients with an ER diagnosis of epileptic seizures, psychogenic non-epileptic seizure (PNES), and syncope were selected for analysis. Serum PRL and LAC concentrations were measured within 3 h of the event and compared between groups., Results: Among the 440 eligible patients, 173 (39.3%) were included for analysis. Serum PRL concentration was significantly higher in patients with epileptic seizures with convulsions than in those with PNES with convulsions (p < 0.001) and convulsive syncope (p = 0.023). Serum LAC concentration was not significantly elevated in patients with convulsive syncope. Using a PRL cut-off value of 24.0 ng/mL, serum PRL concentration had 100.0% sensitivity and 82.9% specificity for differentiating between PNES and other attacks without convulsions., Conclusion: Elevated serum PRL with normal serum LAC concentration in patients who have attacks with convulsions suggests convulsive syncope. Serum PRL concentration is useful in the diagnosis of PNES with convulsions. However, serum LAC concentration is not useful as a routine screening test for attacks without convulsions in the ER., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Legionella pneumophila , an intracellular human pathogen, establishes intracellular relationships with several protist hosts, including Paramecium caudatum . L. pneumophila can escape the normal digestion process and establish intracellular relationships in Paramecium . In this study, we identify new Paramecium strains that significantly reduce the number of L. pneumophila during infection. As a result, stable intracellular relationships between L. pneumophila and these Paramecium strains were not observed. These digestion-type Paramecium also showed high efficiency for Escherichia coli elimination compared to other strains of Paramecium . These results suggest that the digestion-type strains identified have high non-specific digestion activity. Although we evaluated the maturation process of Legionella -containing vacuoles (LCVs) in the Paramecium strains using LysoTracker, there were no discriminative changes in these LCVs compared to other Paramecium strains. Detailed understanding of the mechanisms of high digestion efficiency in these strains could be applied to water purification technologies and L. pneumophila elimination from environmental water., (Copyright © 2020 Watanabe, Higuchi, Shimmura, Tachibana, Fujishima, Shimizu and Watarai.)

Objective: The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal., Methods: The eyes of SDT fatty, SDT (controls), and Sprague Dawley (SD) rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age ( n = 5-6 for each rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm., Results: The retinas tended to be thicker in the SDT fatty rats and SDT rats than in the SD rats; the choroids tended to be thicker in the SDT fatty rats than in the SD rats. The retinal folds in the SDT fatty rats developed earlier and were more severe than in the SDT rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT fatty rats were significantly larger than those of the SDT rats., Conclusions: SDT fatty rats developed more severe DR earlier than the SDT rats. The SDT fatty rats might be useful as a type 2 diabetes animal model to study DR., Competing Interests: All authors declare that there are no conflicts of interest regarding the publication of this paper. Drs. Ohta and Sasase are employees of Japan Tobacco Inc., (Copyright © 2019 Yoshiaki Tanaka et al.)

Objectives: The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures., Methods: Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincaré plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures., Results: Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures., Conclusions: Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.

We evaluated the features of diabetic retinal and choroidal edema in Spontaneously Diabetic Torii (SDT) rats. We measured the retinal and choroidal thicknesses in normal Sprague-Dawley (SD) rats (n = 9) and SDT rats (n = 8). The eyes were enucleated 40 weeks later after they were diagnosed with diabetes, and 4-micron sections were cut for conventional histopathologic studies. The mean retinal and choroidal thicknesses were significantly thicker in the SDT rats than in the normal SD rats. The choroidal thickness was correlated strongly with the retinal thickness in both rat models. Diabetic retinopathy (DR) and diabetic choroidopathy appeared as edema in the SDT rats. The retinal thickness was correlated strongly with the choroidal thickness in the SDT rats, which is an ideal animal model of both DR and choroidopathy.

We report the case of a 17-year-old woman with paroxysmal sympathetic storm (PSS), which was successfully treated with clonidine hydrochloride. The patient was hospitalized for acute disseminated encephalomyelitis in June 2006. Dysphagia led to severe aspiration pneumonia in September 2006, and she suffered cardiopulmonary arrest. She survived but had severe brain damage, with her brain MRI showing diffuse hypoxic encephalopathy. From October 2006, she had several episodes of profound tachypnea (> 60/min), tachycardia (160 to 170 beats/min), hypertension (> 140 mmHg), hyperthermia (39°C), and decerebrate posturing. During the attacks, the levels of catecholamines in the patient's blood and urine were markedly elevated. Accordingly, a diagnosis of PSS associated with hypoxic encephalopathy was made. Her PSS clearly improved after the administration of clonidine hydrochloride (900 μg/day). This case suggests that clonidine hydrochloride, an α2 blocker, may be one therapeutic option for PSS.

A 44-year-old man with a bilateral hand tremor suffered from a decline in concentration and abnormal vision for several months. He also complained of easily falling down because of muscle stiffness and cramps in his lower limbs. On admission, he demonstrated lower limb stiffness, muscle cramps, diplopia, hyperhidrosis, left upper limb ataxia and dysesthesia in all limbs. Laboratory examination showed a marked elevation in his serum creatine kinase level (26,890 U/l), and needle electromyography demonstrated myokymic discharges in the muscles of his lower extremities. Isaacs' syndrome was diagnosed based on a positive voltage-gated potassium channel antibody titer of 1,007 pM. Administration of an anticonvulsant (phenytoin, 200 mg/day) did not resolve his symptoms; however, high-dose intravenous methylprednisolone therapy (1 g/day for 3 days) resulted in marked clinical improvement. This case suggests that high-dose intravenous methylprednisolone therapy for Isaacs' syndrome might be as effective as other immunosuppressive therapies such as plasma exchange or intravenous immunoglobulin.

Purpose: To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats., Methods: The animals were divided into six groups, normal Sprague-Dawley rats (n = 8), untreated SDT rats (n = 9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n = 7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day, n = 7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured., Results: The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP., Conclusion: Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

The concept of transplantation of corneal parts is to replace only diseased tissues, while leaving healthy host tissues intact. Advantages of the new surgical approaches include fast recovery, resistance to trauma, and less postoperative complications. Despite the theoretical benefits, however, only few data are available in terms of the pros and cons of the new surgical methods. In this review, we analyzed our data on deep anterior lamellar keratoplasty (DALK) and Descemet stripping automated endothelial keratoplasty (DSAEK). Difficulty of surgical procedure still remains in DALK, and intraoperative Descemet membrane (DM) rupture is a major concern. We recently introduced a new DM exposure technique: the double-bubble method. We also investigated the influence of DM rupture on graft survival and visual function. Other concerns in DALK are long-term stability of endothelial density and interface opacity. We also investigated safety and efficacy of subsequent cataract surgery and found that the surgery can be performed safely without significant intraoperative complications. Visual improvement was excellent, and endothelial density remained stable. Although recent increase of DSAEK is remarkable, refinements in surgical procedure are needed, especially in Asian small eyes. Recent developments in surgical technique and instruments in graft insertion are presented. DSAEK is advantageous in the management of postoperative complications, including suture-associated troubles, astigmatism, and epithelial damage. However, we encounter new complication such as graft dislocation. Surgical outcomes of our series and those of other institutes are discussed.