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ABSTRACTImmune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein, we report that supplementation with CBM588 led to an improved responsiveness to antibody targeting programmed cell death protein 1 (aPD-1). This was statistically associated with a significant decrease in α-diversity of gut microbiota from CBM588-treated mice upon PD-1 blockade. At the level of the tumor-draining lymph node, such combination of treatment significantly lowered the frequency of microbiota-modulated subset of regulatory T cells that express Retinoic Orphan Receptor gamma t (Ror[Formula: see text]t+ Treg). Specifically, this strongly immunosuppressive was negatively correlated with the abundance of bacteria that belong to the family of Ruminococcaceae. Accordingly, the colonic expression of both indoleamine 2,3-Dioxygenase 1 (IDO-1) and interleukin-10 (IL-10) were heightened in mice with greater PD-1 blockade efficacy. The CBM588-induced ability to secrete Interleukin-10 of lamina propria mononuclear cells was heightened in tumor bearers when compared with cancer-free mice. Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8+ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

Abstract Sepsis is life-threatening organ dysfunction and is considered a major cause of health loss. However, since the current biomarkers of sepsis reflect the host’s immune response to microorganisms, they would inevitably cause a time-lag. This means that there is still no truly reliable biomarker of sepsis. In the present study, we developed a novel method for identifying and quantifying unknown pathogenic bacteria within four hours of sample collection. The most important point of this study is that the novel method can be used to determine the number of bacteria in a sample as a novel biomarker of infectious diseases. Indeed, based on the number of bacteria, we were able to accurately estimate the severity of microbial infection. Furthermore, using the time-dependent changes in the number of bacteria, we were able to monitor the therapeutic effect accurately. The rapid identification and quantification of bacteria may change our approach to medical care.

Abstract To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm−1 vs. 7.89 ± 1.02 mm−1, P = 0.0001), while there wasn’t significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm−1 vs. 2.89 ± 0.22 mm−1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

Abstract Digital phenotyping, particularly the use of plant 3D models, is a promising method for high‐throughput plant evaluation. Although many recent studies on the topic have been published, further research is needed to apply it to breeding research and other related fields. In this study, using a 3D model phenotyping system we developed, we reconstructed and analyzed 20 accessions of zoysiagrass (Zoysia spp.), including three species and their hybrid, over a period of 1 year. Artificial neural network with three hidden layers was able to effectively remove nonplant parts while retaining plant parts that were incorrectly removed using the cropping method, offering a robust and flexible approach for post‐processing of 3D models. The system also demonstrated its ability to accurately evaluate a range of traits, including height, area, and color using red green blue (RGB)‐based vegetation indices. The results showed a high correlation between the estimated volume obtained from voxel 3D model and dry weight, enabling its use as a non‐destructive method for measuring plant volume. In addition, we found that the green red normalized difference index from RGB‐based indices was similar to the commonly used normalized difference vegetation index in controlled illumination conditions. These results demonstrate the potential for three‐dimensional model phenotyping to facilitate plant breeding, particularly in the field of turfgrass and feed crops.

This study investigates the change in horizontal saccadic eye movement and smooth pursuit in patients with acquired comitant esotropia (ACE), before and after strabismus surgery. The horizontal saccades and pursuit in 11 patients with ACE were recorded using a video eye-tracker under binocular viewing before and after strabismus surgery. Participants were instructed to fixate on the new target as rapidly as possible when it randomly appeared at either 18.3° rightward or 18.3° leftward. For smooth pursuit, participants were asked to track, as accurately as possible, a step-ramp target moving at ±6.1°/s. The asymmetry of adduction-abduction and the binocular coordination in gains of saccade and pursuit were compared between the pre- and post-surgical data. The asymmetry of adduction-abduction saccade gain in each eye after surgery tended to be smaller than that before surgery. The binocular coordination of saccade showed significant improvement after surgery in only the non-dominant eye direction. Adduction-abduction asymmetry in the smooth pursuit gain in each eye after surgery tended to be smaller than before surgery. After surgery, the binocular coordination of pursuit was improved significantly in both directions. In patients with ACE, binocular coordination of saccade and smooth pursuit was poor. Binocular coordination of saccade and pursuit seems to be improved due to the improvement in ocular deviation angle and binocular visual function after surgery.

Purpose: We describe the cases of two patients for whom we performed an epiretinal proliferation (EP) embedding technique combined with internal limiting membrane (ILM) flap inversion for a full-thickness macular hole (FTMH) with EP. Observations: Patient 1 was a 69-year-old Japanese man with decreased vision in his left eye (20/40). He underwent pars plana vitrectomy (PPV) twice for rhegmatogenous retinal detachment and intraocular lens (IOL) dislocation in his left eye. B-scan optical coherence tomography (OCT) imaging revealed FTMH and EP on the surface of a macular hole (MH). We performed a vitrectomy, EP embedding, and ILM inversion (fill). Patient 2 was a 73-year-old Japanese man with decreased vision in his right eye (20/32). He underwent PPV for vitreous hemorrhage and proliferative diabetic retinopathy in his right eye. B-scan OCT imaging revealed FTMH and EP on the surface of an MH. We performed a vitrectomy, EP embedding, and ILM inversion (cover). Six months post-surgery, the FTMH in both patients had closed completely, and each patient's foveal contour and visual acuity (20/20) had improved. Conclusions and importance: EP embedding combined with ILM flap inversion may be effective for treating secondary MHs with EP.

Deep learning (DL) has become a remarkably powerful tool for image processing recently. However, the usefulness of DL in positron emission tomography (PET)/computed tomography (CT) for breast cancer (BC) has been insufficiently studied. This study investigated whether a DL model using images with multiple degrees of PET maximum-intensity projection (MIP) images contributes to increase diagnostic accuracy for PET/CT image classification in BC. We retrospectively gathered 400 images of 200 BC and 200 non-BC patients for training data. For each image, we obtained PET MIP images with four different degrees (0°, 30°, 60°, 90°) and made two DL models using Xception. One DL model diagnosed BC with only 0-degree MIP and the other used four different degrees. After training phases, our DL models analyzed test data including 50 BC and 50 non-BC patients. Five radiologists interpreted these test data. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Our 4-degree model, 0-degree model, and radiologists had a sensitivity of 96%, 82%, and 80–98% and a specificity of 80%, 88%, and 76–92%, respectively. Our 4-degree model had equal or better diagnostic performance compared with that of the radiologists (AUC = 0.936 and 0.872–0.967, p = 0.036–0.405). A DL model similar to our 4-degree model may lead to help radiologists in their diagnostic work in the future.

Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

Purpose: We report the case of a 32-year-old woman with orbital myositis prior to onset of Behcet's disease (BD). Observations: A 32-year-old woman was referred to our hospital for a complaint of right eyelid swelling, eye pain, and diplopia. Her best-corrected visual acuity was 20/32 on the right, and 20/16 on the left. She was diagnosed as idiopathic orbital inflammation, and received two pulses of intravenous administration of methylprednisolone, followed by oral prednisolone. Three months later, she developed bilateral orbital myositis, and received one more pulse therapy, followed by oral prednisolone and cyclosporin. About one year after the first visit, oral aphthae, genital ulcers, and folliculitis-like skin rash appeared, and the physician diagnosed incomplete type BD. The patient had no uveitis during the disease course. Orbital inflammation and systemic manifestations of BD were ultimately well controlled with small doses of prednisolone. Conclusion and importance: BD may develop during the course of orbital inflammation.

Three-dimensional measurement is a high-throughput method that can record a large amount of information. Three-dimensional modelling of plants has the possibility to not only automate dimensional measurement, but to also enable visual assessment to be quantified, eliminating ambiguity in human judgment. In this study, we have developed new methods that could be used for the morphological analysis of plants from the information contained in 3D data. Specifically, we investigated characteristics that can be measured by scale (dimension) and/or visual assessment by humans. The latter is particularly novel in this paper. The characteristics that can be measured on a scale-related dimension were tested based on the bounding box, convex hull, column solid, and voxel. Furthermore, for characteristics that can be evaluated by visual assessment, we propose a new method using normal vectors and local curvature (LC) data. For these examinations, we used our highly accurate all-around 3D plant modelling system. The coefficient of determination between manual measurements and the scale-related methods were all above 0.9. Furthermore, the differences in LC calculated from the normal vector data allowed us to visualise and quantify the concavity and convexity of leaves. This technique revealed that there were differences in the time point at which leaf blistering began to develop among the varieties. The precise 3D model made it possible to perform quantitative measurements of lettuce size and morphological characteristics. In addition, the newly proposed LC-based analysis method made it possible to quantify the characteristics that rely on visual assessment. This research paper was able to demonstrate the following possibilities as outcomes: (1) the automation of conventional manual measurements, and (2) the elimination of variability caused by human subjectivity, thereby rendering evaluations by skilled experts unnecessary.

Localized amyloidosis of the lacrimal gland is a rare disease. We report a case of transthyretin-positive localized amyloidosis of the lacrimal gland in a 74-year-old man with left lacrimal gland swelling. Biopsy of the left lacrimal gland showed extensive deposition of nonstructural eosinophilic material in the secretory gland and ducts, which stained positive with direct fast scarlet. Immunostaining was negative for amyloid A and positive for both globulin light chain (kappa, lambda) and transthyretin. It is necessary to consider the possibility of senile systemic amyloidosis, even if localized amyloidosis of the lacrimal gland is suspected.

Local adaptation contributes to plant colonization across extreme environmental gradients. Here, the authors reconstruct the colonization history of Lotus japonicus in Japan and identify extreme genetic signatures of local adaptation to a cold climate using genome resequencing and common garden experiments.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn’s disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

The most common sites of IgG4-related ocular disease are the lacrimal glands, infraorbital nerve, and extraocular muscles. Other ocular adnexal sites are relatively rare. We report a rare case of an 83-year-old man who developed palpebral conjunctivitis following bilateral hypertrophic ectropion of the eyelid. Tissue immunostaining revealed many IgG4-positive plasma cells (67 IgG4/74 IgG cells/high-power field). The serum IgG4 level was 76.9 mg/dL, which was within the normal range. The diagnosis was probable IgG4-related disease. The possibility of IgG4-related disease should be considered in a patient presenting with refractory conjunctivitis and hyperemia or hypertrophy of the lower eyelid.

Purpose: We investigated the factors influencing the morphology of filtration blebs after Ex-PRESS® surgery. We analyzed the thickness of the bleb wall and the height and the volume of blebs. Methods: This was a retrospective non-randomized study. After excluding patients who had undergone an additional glaucoma surgery, we analyzed the cases of 145 consecutive patients (180 eyes) who underwent trabeculectomy with Ex-PRESS® for the first time at Toyama University Hospital and were followed for >1 year. We used anterior segment optical coherence tomography to analyze the morphology of the blebs after Ex-PRESS surgery. We also examined potential influencing factors including age, central corneal thickness, type of glaucoma (primary open-angle glaucoma [POAG] or pseudo-exfoliation glaucoma [PEXG]), preoperative intraocular pressure (IOP), postoperative IOP, history of trabeculotomy, and operation method: Ex-PRESS surgery only, or simultaneous cataract surgery. Results: Ex-PRESS surgeries significantly decreased the IOP from 24.5 ± 8.8 mmHg to 11.1 ± 3.4 mmHg after 1 year (P < 0.001). The cases with higher blebs, larger volume of blebs, and thinner bleb wall had better surgical outcomes. Conclusion: Advanced age, higher postoperative IOP, PEXG, and simultaneous cataract surgeries were found to decrease the volume and height of blebs. Younger age, higher postoperative IOP, POAG, and simultaneous cataract surgeries were found to thicken the wall of blebs. Among the younger patients, there were many cases in which surgery was unsuccessful in spite the large volume of blebs. The reason for this may be that the wall of the bleb is thick.

Purpose. To evaluate early effects of hydroxychloroquine (HCQ) on the retina using adaptive optics (AO). Methods. This was a prospective observational single-center study of 29 eyes of 29 patients who had been treated with HCQ for the first time and followed with AO for a minimum of two years. Cone counting was performed in 4 quadrants, nasal, temporal, superior, and inferior, at 0.75 mm from the foveal center. The changes of cone density on AO, visual acuity, and foveal thickness within two years of use were analyzed. The changes of mean cone density of patients whose cumulative dose was over 200 g in 2 years were also assessed. We evaluated the correlation between cone density and cumulative dose of HCQ. Results. There was no significant decrease in cone density in the first 2 years of HCQ use. VA and foveal thickness did not show obvious change, either. Among 9 patients whose cumulative dose was over 200 g in 2 years, the mean cone density showed no significant change at 6, 12, 18, and 24 months compared with baseline (P=0.381, P=0.380, P=0.281, and P=0.534, respectively). There was no correlation between cone density and cumulative dose of HCQ at two years (Spearman’s correlation coefficient, r = −0.0553, P=0.780; n = 29). Conclusion. AO showed no change in cone density in the first two years of HCQ use.

Gut dysbiosis associated with intestinal inflammation is characterized by the blooming of particular bacteria such as adherent-invasive E. coli (AIEC). However, the precise mechanisms by which AIEC impact on colitis remain largely unknown. Here we show that antibiotic-induced dysbiosis worsened chemically-induced colitis in IL-22-deficient mice, but not in wild-type mice. The increase in intestinal inflammation was associated with the expansion of E. coli strains with genetic and functional features of AIEC. These E. coli isolates exhibited high ability to out compete related bacteria via colicins and resistance to the host complement system in vitro. Mutation of wzy, the lipopolysaccharide O polymerase gene, rendered AIEC more sensitive to the complement system and more susceptible to engulfment and killing by phagocytes while retaining its ability to outcompete related bacteria in vitro. The wzy AIEC mutant showed impaired fitness to colonize the intestine under colitic conditions, but protected mice from chemically-induced colitis. Importantly, the ability of the wzy mutant to protect from colitis was blocked by depletion of complement C3 which was associated with impaired intestinal eradication of AIEC in colitic mice. These studies link surface lipopolysaccharide O-antigen structure to the regulation of colitic activity in commensal AIEC via interactions with the complement system.

Objective: To provide information on the clinical characteristics and management of an uncommon acquired nasolacrimal drainage system obstruction (NLDSO).Methods: A patient was treated with microdebrider-assisted endoscopic marsupialization for a cystic lesion located in the synechiae between the inferior turbinate and the lateral wall of the inferior meatus.Results: A 21-year-old woman suffered from epiphora and purulent discharge 1 week after inferior turbinate surgery. Endoscopy reveled synechiae between the inferior turbinate and the lateral wall of the inferior meatus. Computed tomography-dacrocystography (CT-DCG) showed enlargement of the nasolacrimal duct and cystic accumulation of contrast medium from the lacrimal orifice posteriorly. The patient was treated with nasal endoscopic marsupialization of the cyst and then powered inferior turbinoplasty. Six months after the operation, both endoscopy and CT scan showed a widely patent left inferior meatus and nasolacrimal orifice.Conclusions: We report the first case of post-operative NLDSO following inferior turbinate surgery. Nasal endoscopy and CT-DCG are useful to diagnose the location of a NLDSO. Otorhinolaryngologists should be aware that surgery may lead to the formation of a NLDSO and that endoscopic marsupialization is a curative treatment for these distal-end NLDSO. NLDSOs are caused by synechiae, which are a complication of inferior turbinate surgery.

Purpose: We report the case of an 11-year-old boy with posterior microphthalmos who exhibited normal and age appropriate development of visual acuity. Observations: At the initial diagnosis, when he was 3 years old, the best-corrected visual acuity (BCVA) was 20/125 in the right eye (OD) and 20/200 in the left eye (OS) with high hyperopia (cycloplegic refraction +15.75 D sphere OD and +16.25 D sphere OS). Eight years after he began wearing hyperopic glasses, BCVA was 20/16 OD and 20/20 OS. Optical coherence tomography did not reveal a foveal pit in either eye throughout the observation period. However, elongation of the outer segment and widening of the outer nuclear layers were observed. Conclusion and Importance: Many cases of posterior microphthalmos demonstrate subnormal BCVA due to an abnormal foveal structure (papillomacular retinal folds, absence of the foveal pit and avascular zone) and high hyperopia. However, if foveal maturity progresses, even if the foveal structure is abnormal, early aggressive amblyopia treatment can result in normal and age appropriate development of visual acuity. Keywords: Posterior microphthalmos, Fovea, Hypoplasia, Amblyopia, OCT, Hyperopia

Purpose: To report 2 cases of central retinal artery occlusion (CRAO) who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA) into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. Methods: Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL) solution was injected into the retinal artery of the optic disc for 2–3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT), fluorescein angiography, and laser speckle flowgraphy (LSFG) results were examined. Results: Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. Conclusions: Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO.

Summary: Gut-derived microbial antigens trigger the innate immune system during acute liver injury. During recovery, regulatory immunity plays a role in suppressing inflammation; however, the precise mechanism underlying this process remains obscure. Here, we find that recruitment of immune-regulatory classical dendritic cells (cDCs) is crucial for liver tolerance in concanavalin A-induced acute liver injury. Acute liver injury resulted in enrichment of commensal Lactobacillus in the gut. Notably, Lactobacillus activated IL-22 production by gut innate lymphoid cells and raised systemic IL-22 levels. Gut-derived IL-22 enhanced mucosal barrier function and promoted the recruitment of regulatory cDCs to the liver. These cDCs produced IL-10 and TGF-β through TLR9 activation, preventing further liver inflammation. Collectively, our results indicate that beneficial gut microbes influence tolerogenic immune responses in the liver. Therefore, modulation of the gut microbiota might be a potential option to regulate liver tolerance. : Nakamoto et.al. find that Lactobacillus accumulates in the gut and activates IL-22 production by innate lymphoid cells during acute liver injury. Gut-derived IL-22 contributes to liver tolerance via induction of regulatory DCs. Keywords: immune tolerance, dendritic cell, innate lymphoid cell, acute liver injury, interleukin-10, interleukin-22, microbiota, dysbiosis

Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut. Consistently, L. murinus induced alopecia when monocolonized in germ-free mice fed a biotin-deficient diet. Supplementation of biotin can reverse established alopecia symptoms in the SPF condition, indicating that L. murinus plays a central role in the induction of hair loss via a biotin-dependent manner. Collectively, our results indicate that luminal metabolic alterations associated with gut dysbiosis and dietary modifications can compromise skin physiology.

Purpose: To report a successful eyelid reconstruction performed using the residual tarsus after excision of a sebaceous gland carcinoma. Case Report: An 86-year-old woman presented with a sebaceous gland carcinoma of the upper eyelid margin. After excision of the tumor, she underwent reconstructive surgery of the superior eyelid performed using the residual tarsus. Because the tumor was localized on the upper lid margin, a tarsus of about 4–5 mm in height remained after the excision; we therefore used the residual tarsus to reconstruct the upper eyelid. No functional or cosmetic problems arose as a result of this method. Conclusions: Reconstructive surgery of the upper eyelid using the residual tarsus may be a viable option provided that surgeons can ensure a sufficient safety margin, and that more than 4 mm of the tarsus remains.

Purpose. The effects of strabismus surgery on eye movement are not known in detail, as few studies have compared saccade velocities before and after strabismus surgery. In this study, horizontal saccades were recorded using an eye-tracker in patients with only exotropia to compare the peak velocities (PVs), before and after undergoing strabismus surgery of the same type (unilateral resection and recession). Methods. Horizontal saccades of monocular vision were recorded using an eye-tracking device in 18 patients with exotropia and 20 normal subjects. All patients were examined using the same method after strabismus surgery. Results. The PVs of adduction and abduction in the patients were higher than those in the normal subjects (in dominant eye, P=0.032 for adduction and P=0.049 for abduction; in nondominant eye, P=0.016 for adduction and P=0.037 for abduction). Following the surgery, the PVs of abduction of the surgical eye (nondominant eye) decreased to the level of the normal subjects (P=0.016). However, there were no correlations between changes in the PVs and the extent of surgery (resection and recession). Conclusion. Strabismus surgery normalized the patient’s increased PV in the operated eye for abduction of horizontal saccade. Not only peripheral (extraocular muscle) but also central sensory-motor mechanisms may be involved in the changes in PV of horizontal saccades, both of which could result from the improvement of the primary eye position.

Purpose. To examine the prognostic factors related to postoperative visual acuity in patients with rhinogenic optic neuropathy. Study Design. Retrospective observational study. Materials and Methods. We retrospectively studied the medical records for 15 eyes of 15 patients who underwent surgery for the treatment of rhinogenic optic neuropathy between 31 January 2010 and 30 April 2018 at Toyama University Hospital. The patient age, sex, preoperative and postoperative visual acuity, duration from visual deficit to surgery, use of steroids, type of rhinogenic optic neuropathy, and the part of sinus lesion were analyzed. We also examined postoperative visual acuity for patients whose preoperative visual acuity was less than light perception. Results. The type of optic neuropathy was sinusitis in 7 cases, mucocele in 5 cases, and pyocele in 3 cases. Visual acuity was improved in 9 cases and deteriorated or unchanged in 6 cases. Patients in the improvement group were significantly younger than those in the nonimprovement group (p=0.01). In univariate regression analysis, preoperative visual acuity and type of optic neuropathy significantly related to postoperative visual acuity. Finally, 4 of the 15 cases (27%) had preoperative visual acuity less than light perception, but there was an improvement in postoperative visual acuity in 2 of 4 cases (50%). Conclusions. Preoperative visual acuity is the predictive factor for postoperative visual acuity in patients with rhinogenic optic neuropathy, but even if the preoperative visual acuity is less than light perception, it can be improved by surgical treatment.

Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding of agonist glutamate and coagonist glycine or D-serine. D-Serine is produced from L-serine by serine racemase (SRR) and contributes to retinal neurodegeneration in rodent models of DR. However, the involvement of SRR in both neurodegeneration and microvascular damage in DR remains unclear. Here, we established diabetic model of SRR knockout (SRR-KO) and control wild-type (WT) mice by streptozotocin injection. Six months after the onset of diabetes, the number of survived retinal ganglion cells was higher in SRR-KO mice than that of WT mice. The reduction of thickness of inner retinal layer (IRL) was attenuated in SRR-KO mice than that of WT mice. Moreover, the number of damaged acellular capillaries was lower in SRR-KO mice than that of WT mice. Our results suggest the suppression of SRR activity may have protective effects in DR.

Background: With the development of laparoscopic instruments such as the morcellator, a large number of gynecologists have performed laparoscopic myomectomies. In this study, we reviewed all cases in which residual myomas were identified by follow-up magnetic resonance imaging in order to evaluate why any myomas would remain after a laparoscopic myomectomy and to find their most common location and depth within the uterus. Methods: Patients (n = 128) with uterine myomas who underwent a laparoscopic myomectomy between 2008 and 2011 and received follow-up magnetic resonance imaging 3 months afterward were reviewed retrospectively. We analyzed the influence of preoperative gonadotrophin-releasing hormone agonist treatment, as well as the location and depth of the residual myomas within the uterus. The pregnancy rate in all cases was also investigated. Results: The duration of the preoperative administration of gonadotrophin-releasing hormone agonist was statistically longer in cases where multiple residual myomas were found, compared with cases where a single residual myoma was present. There was no statistical difference in the rate and size of the residual myomas among five different locations within the uterus. The rate of residual subserosal myomas was lowest, compared with two other types, and was statistically lower than residual intramuscular myomas (p

Purpose: To report a case of varicella-zoster virus (VZV) keratitis with detection of VZV DNA in the tear fluid of not only the symptomatic eye but also the contralateral asymptomatic eye by polymerase chain reaction (PCR). Methods: This is a case report. A 63-year-old otherwise healthy woman presented with circular corneal ulcer and stromal opacity with infiltration accompanied by mild conjunctival and ciliary injections in the left eye. Bacterial cultures of the corneal scrapings and virus PCR analyses of tear fluid from both eyes were performed. Results: No pathogen was found by bacterial cultures. PCR was negative for Acanthamoeba, herpes simplex virus and cytomegalovirus, but positive for VZV. VZV DNA was also detected in the unaffected eye. Based on the diagnosis of VZV keratitis, oral valacyclovir and acyclovir eye ointment were administered to the corneal infected eye. The infected eye was healed and VZV DNA turned negative in the tear fluid of the treated eye after 6 months of treatment; however, VZV DNA was still positive in the tear fluid of the contralateral eye. Conclusions: To our knowledge, this is the first case report of the detection of VZV DNA in the tear fluid of both affected and unaffected eyes in a patient with VZV keratitis. Asymptomatic conjunctival shedding of VZV may continue in the healthy unaffected eye in VZV keratitis patients.

Purpose: To examine anatomical changes in idiopathic macular holes during surgery using handheld spectral-domain optical coherence tomography (SD-OCT). Methods: Five eyes of 5 patients who underwent surgery for the repair of idiopathic macular holes were examined. The surgery included standard 25-gauge, 3-port pars plana vitrectomy, removal of the internal limiting membrane (ILM), fluid-air exchange, and 20% sulfur hexafluoride tamponade. Intraoperative SD-OCT images of the macular holes were obtained after ILM removal and under fluid-air exchange using a handheld SD-OCT. From SD-OCT images, the macular hole base diameter (MHBD) was measured and compared. Results: All macular holes were successfully closed after the primary surgery. The mean MHBD under fluid-air exchange was significantly smaller than the mean MHBD after ILM removal and the preoperative mean MHBD. In 1 eye with a stage 3 macular hole, SD-OCT images revealed that the inner edges of the macular hole touched each other under fluid-air exchange. Conclusion: Fluid-air exchange significantly reduced MHBD during surgery to repair macular holes. Fluid-air exchange may be an important step for macular hole closure as it reduces the base diameter of the macular hole.

Purpose: To report surgical results of canaloplasty surgery for primary open-angle glaucoma (POAG) in Japanese patients. Methods: Eleven eyes of 9 POAG patients underwent canaloplasty surgery at Toyama University Hospital. Three eyes of 3 patients underwent canaloplasty alone and 8 eyes of 6 patients underwent canaloplasty combined with cataract surgery. Canaloplasty was performed with a 10-0 polypropylene tensioning suture and an iTrack™ 250A microcatheter. All patients were followed up for 12 months. Changes in intraocular pressure (IOP) and postoperative complications were examined. Results: Mean preoperative IOP was 23.4 ± 5.5 mm Hg. Mean number of antiglaucoma drops was 2.8 ± 0.6 before canaloplasty and decreased to 1.2 ± 0.8 at 12 months after canaloplasty (p Conclusions: Canaloplasty may be an alternative surgery for POAG patients to reduce IOP to a value of approximately 15 mm Hg.

Purpose. To evaluate the efficacy of setting a preferred retinal locus relocation target (PRT) and performing Macular Integrity Assessment (MAIA) biofeedback training in patients showing insufficient recovery of best corrected visual acuity (BCVA) despite successful closure of an idiopathic macular hole (MH). Methods. Retrospective interventional case series. Nine eyes of 9 consecutive patients with the decimal BCVA of less than 0.6 at more than 3 months after successful MH surgery were included. A PRT was chosen based on MAIA microperimetry and the patients underwent MAIA biofeedback training. BCVA, reading speed, fixation stability, and 63% bivariate contour ellipse area (BCEA) were evaluated before and after the training. Statistical analysis was carried out using paired Student’s t-test. Results. PRT was chosen on the nasal side of the closed MH fovea in 8 patients. After the MAIA training, BCVA improved in all patients. The mean logMAR value of BCVA significantly improved from 0.33 to 0.12 (p=0.007). Reading speed improved in all patients (p=0.29), fixation stability improved in 5 patients (p=0.70), and 63% BCEA improved in 7 patients (p=0.21), although these improvements were not statistically significant. Conclusion. MAIA biofeedback training improved visual acuity in patients with insufficient recovery of BCVA after successful MH surgery.

The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2(-/-) mice adoptively transferred with CD4(+)CD45RB(high) T cells; and IL-10(-/-) mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b(-)CD11c(low)PDCA-1(+) plasmacytoid dendritic cells (DCs) abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) mice and IL-10(-/-) mice in parallel with the emergence of macrophages (Mφs) and conventional DCs (cDCs). Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4(+) T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS)-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation.

Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis.

Purpose. To evaluate the effects of pars plana vitrectomy (PPV) on recurrent macular edema due to branch retinal vein occlusion (BRVO) after intravitreal injections of bevacizumab (IVB). Methods. This retrospective study included 22 eyes of 22 patients who underwent single or multiple IVB injections for macular edema due to BRVO and showed a recurrence of macular edema. All patients then underwent PPV and were followed up for more than 6 months after the surgery with examinations of best corrected visual acuity (BCVA) and optical coherence tomography (OCT). OCT parameters were central macular thickness (CMT) and average retinal thickness in a 1-mm-diameter circular region at the fovea (MRT). Results. Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV. Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than after 6 months of PPV. No eyes showed worsening of macular edema after the surgery. Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO, but PPV that was less effective than IVB had been in the same patients. PPV may be one of the treatment options for recurrent macular edema due to BRVO after IVB.

This paper presents a micro-coordinate measuring machine (micro-CMM) for large-scale dimensional measurement of a micro-slit on a precision die coater by using a shear-mode micro-probe. A glass micro sphere with a nominal diameter of 52.3 μm was attached on one end of a tapered glass capillary tube as a probe tip ball. The micro-slit width of a slot die coater with a nominal slit width of 85 μm was measured by the micro-CMM. The probe tip was placed in the slit for the measurement. The effective working length of the probe was confirmed experimentally to be at least 1 mm. In order to measure the gap width uniformity over the entire slot die length of 200 mm, an air-bearing linear slide with a travelling stroke of 300 mm was employed in the micro-CMM to position the probe along the length direction of the slot die. The angular alignment error and the motion error of the air-bearing linear slide as well as those of the stages for positioning the probe along the direction perpendicular to the length direction of the slot die were investigated for evaluation of the expanded uncertainty of gap width measurement.

Purpose. To evaluate the effects of photodynamic therapy (PDT) combined with intravitreal injection of ranibizumab (IVR) for exudative age-related macular degeneration (AMD). Methods. Retrospective case series. Thirty eight eyes of 38 patients with exudative AMD underwent combined therapy consisting first of IVR, followed by PDT within a week and the second IVR at 1 month. All patients were followed up for more than 12 months. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were examined. Results. The mean number of IVR and PDT sessions were 2.9±1.3 and 1.1±0.3, respectively. The mean BCVA and CMT were significantly improved to 0.38 logMAR units (𝑃