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Subthreshold micropulse laser (SMPL) is more clinically efficient for the treatment of diabetic macular edema (DME) than the conventional continuous-wave (CW) laser. We aimed to characterize transcriptome changes after the application of these lasers and to compare the transcripts.Human pluripotent stem cell-derived retinal pigment epithelial cells were exposed to laser irradiation. Differentially expressed genes (DEGs), distribution of heat shock protein (Hsp) family, gene expression profile, and gene ontology (GO) enrichment analysis based on RNA sequencing data were investigated at 3 h and 24 h after irradiation.CW laser induced more DEGs than SMPL (1771 vs. 520 genes). The expression of the Hsp family was confirmed in both groups: however, the induction patterns was different for different genes. GO enrichment analysis revealed that CW laser upregulated the expression of DEGs involved in vasculature development (GO: 0001944), related to apoptosis and repair after cell injury whereas SMPL upregulated the expression of DEGs involved in photoreceptor cell maintenance (GO: 0045494), photoreceptor cell development (GO: 0042461), and sensory perception of light stimuli (GO: 0050953).The results provide insights into the genetic responses and may contribute to the understanding of the molecular mechanisms of laser-induced thermal effects.

To evaluate the histological changes associated with, and the potential mechanisms of, intraocular pressure (IOP) reduction by micropulse cyclophotocoagulation (MP-CPC) in rabbit eyes.MP-CPC was performed on the right eyes of Dutch belted rabbits, whereas the left eyes served as controls. The laser power settings were 250, 500, 750, 1000, 1500, and 2000 mW, 10 seconds per sweep, 100 seconds in total. IOP, outflow facility, and uveoscleral outflow tract imaging, using a fluorescent tracer, were examined at one week after MP-CPC. Changes of morphology and protein expressions in the outflow tissues, conjunctiva, and sclera were also evaluated.Significant reductions in IOP after MP-CPC were observed at 500 to 1000 mW (P = 0.036 and P = 0.014, respectively). The pre-MP-CPC IOP was 11.35 ± 0.41 mm Hg. At one week after surgery, the respective IOP values in the eyes treated at 500 mW and 1000 mW were 9.45 ± 0.49 mm Hg and 7.4 ± 0.27 mm Hg, respectively. Severe ciliary body damage was observed at 1500 to 2000 mW. MMP1-3 and fibronectin expression levels in the outflow tract and ciliary body were upregulated after MP-CPC. The α-smooth muscle actin (α-SMA) was upregulated at higher power levels. MP-CPC significantly increased uveoscleral outflow, whereas the outflow facility did not change. The α-SMA, collagen, and fibronectin were significantly upregulated in the subconjunctiva and sclera.Reactive fibrotic responses were observed in the outflow tract, conjunctiva, and sclera after MP-CPC. A potential mechanism of IOP reduction by MP-CPC in pigmented rabbit eyes may involve increased uveoscleral outflow related to MMP upregulation.

Higher cortisol levels due to a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p

It is sometimes difficult to differentiate between high signals originating from a reverse flow on magnetic resonance angiography (MRA) and occult arteriovenous shunting. We attempted to determine whether arterial spin labeling (ASL) can be used to discriminate reversal of venous flow from arteriovenous shunting for high-signal venous sinuses on MR angiography. Two radiologists evaluated the signals of the venous sinus on MRA and ASL obtained from 364 cases without arteriovenous shunting. In addition, the findings on MRA were compared with those on ASL in an additional 13 patients who had dural arteriovenous fistula (DAVF). In the 364 cases (728 sides) without arteriovenous shunting, a high signal due to reverse flow in the cavernous sinuses (CS) was observed on 99 sides (13.6%) on MRA and none on ASL. Of these cases, a high signal in the sigmoid sinus, transverse sinus, and internal jugular vein was seen on 3, 3, and 8 sides, respectively. All of these venous sinuses showed a high signal from the reverse flow on MRA images. ASL is a simple and useful MR imaging sequence for differentiating between reversal of venous flow and CS DAVF. In the sigmoid and transverse sinus, ASL showed false-positives due to the reverse flow from the jugular vein, which may be a limitation of which radiologists should be aware.

To compare the short-term surgical effectiveness and safety profile of ab interno trabeculotomy using 2 types of trabecular hooks. Retrospective comparative study. A retrospective chart review was performed on Japanese open-angle glaucoma patients who underwent ab interno trabeculotomy with phacoemulsification and who had a 6-month follow-up. Trabeculotomy was performed using 2 kinds of trabecular hooks, the Tanito ab interno Trabeculotomy Micro-hook (TMH) or the Kahook Dual Blade (KDB). The patients’ demographics, preoperative and postoperative intraocular pressures (IOPs), medication scores, and occurrence of complications were analyzed and compared. Fifty-nine eyes with open-angle glaucoma were included in the final analysis. Trabeculotomy was performed using the TMH in 30 eyes (50.8%) and the KDB in 29 eyes (49.2%). Significant decreases in IOP from the baseline (P

To evaluate the effectiveness of MicroPulseRetrospective study METHODS: We analyzed the data of patients with refractory glaucoma who underwent MP-TLT with the original and with the revised MicroPulse P3This study enrolled 40 patients in both probe groups. At baseline, the mean IOP was 31.1 mmHg in the original group and 29.2 mmHg in the revised group, and it decreased to 22.6 mmHg and 21.6 mmHg after 3 months, respectively (paired t-test p=0.001, 0.001). No significant difference was noted between the number of medications and BCVA at baseline and 3 months in either probe group (paired t-test, p0.05). Nor were any serious complications observed.MP-TLT using the revised MicroPulse P3

We developed a sensor-integrated eye surgical simulator for inner limiting membrane (ILM) peeling, a complicated intraocular surgery. For the quantitative characterization of the retinal surgical skills, we first introduced a quartz crystal resonator (QCR) force sensor that exhibits the high sensitivity, the dynamic range, and the rigidity. The dynamic range of the simulator with this sensor was from 0.087 mN to 7.7 N. We subsequently achieved the uniformity of the force sensitivity on the retinal area of ILM peeling by the parallel mechanical suspension and double ends flexure of the QCR sensor. The error proportion of the sensitivity in that retinal area was suppressed within ±14 %. Finally, we demonstrated the practical evaluation of ILM peeling on the training platform.

Purpose The purpose of this work was to report a new method for the repair of ischemic bleb leaks. Bleb leakage is a serious complication of glaucoma filtering surgery with mitomycin C. Many surgical methods have been proposed to seal the leakage from a bleb; however, this novel plication method is effective, relatively easy to perform, and safe. Methods We describe the case reports of 2 patients with leakage from a bleb who were treated with the new method. The conjunctiva was lifted away from the sclera as extensively as possible around the ischemic conjunctiva toward the fornix using a bleb knife. Thereafter, 10-0 nylon sutures were applied between the nonischemic conjunctiva located just outside the ischemic conjunctiva and the corneal limbus. The ischemic conjunctiva was not removed, but covered with the nonischemic conjunctiva that was advanced toward the corneal limbus by these sutures. Results After treatment, no recurrence of bleb leakage was observed. Moreover, no ischemic changes were observed in the advanced nonischemic conjunctiva or plicated conjunctiva. Conclusion This new method of bleb plication was effective for sealing bleb leakage.

Purpose: Compared with healthy subjects (HS), patients with major depressive disorder (MDD) exhibit volume differences that affect the volume changes in several areas such as the limbic, cortical, subcortical, and white matter. Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes endogenous catecholamines. The Val158Met polymorphism of COMT has been reported to affect the dopamine (DA) levels, which plays an important role in psychiatric diseases. However, the relationships among both DA levels, COMT genotype, and brain morphology are complicated and controversial. In previous studies that investigated the hippocampal subfields, the greatest brain abnormalities in MDD patients were observed in Cornu Ammonis (CA)1 and the subiculum, followed by that in CA2-3. We have prospectively demonstrated the relationship between the single-nucleotide polymorphism of the Val158Met COMT gene (rs4680) and the hippocampal subfields in drug-naive MDD patients. Patients and methods: In this study, we compared 27 MDD patients and 42 HS who were divided into groups based on their COMT genotype. The effects of the diagnosis, genotype, and genotype-diagnosis interaction related to CA1 and the subiculum volumes, as well as the whole-brain cortical thickness, were evaluated by performing a FreeSurfer statistical analysis of high-resolution magnetic resonance imaging (MRI) findings. Results: The results revealed that there was a statistically significant interaction between the effects of diagnosis and genotype on the right subiculum (a component of the hippocampus). Conclusion: This Val158Met COMT polymorphism may influence the subiculum volume in drug-naive, first-episode MDD patients.

To investigate optimal beam quality for chest flat panel detector (FPD) system by semi-quantitatively assessment using a realistic lung phantom. Chest FPD radiographs were obtained on a realistic lung phantom with simulated lung opacities using various X-ray tube voltage levels (90–140 kV) with/without copper filter. Entrance skin dose was set to maintain identical for all images (0.1 mGy). Three chest radiologists unaware of the exposure settings independently evaluated the image quality of each simulated opacity and normal structure using a 5-point scale (+ 2: clearly superior to the standard; + 1: slightly superior to the standard; 0: equal to the standard; − 1: slightly inferior to the standard; − 2: clearly inferior to the standard). The traditional FPD image obtained at a tube voltage of 120 kV was used as the standard. The scores of image quality were statistically compared using the Wilcoxon rank test with Bonferroni correction. FPD images using 90-kV shot with copper filter were superior to the traditional 120-kV shot without filter with respect to the visibility of vertebra, pulmonary vessels, and nodules overlapping diaphragm and heart (p

Background Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. Methods One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. Results The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p Conclusions Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

The purpose of the study was to evaluate the 12-month surgical outcome and prognostic factors of stand-alone ab interno trabeculotomy. The changes in the intraocular pressure (IOP) and medication score and the success rate of the surgery were analyzed. Thirty-four eyes of 29 patients with primary open-angle glaucoma (POAG; n = 16) or pseudoexfoliation glaucoma (PEG; n = 18) with a 12-month follow-up period were included in the study. The decreases in IOP and medication score from the baseline to the all-time-point were statistically significant (P < 0.001). The surgical success rates were 97.1%, 76.5%, and 44.0% at 3 months (90 days), 6 months (180 days), and 12 months (365 days), respectively. A mixed effect Cox model revealed that the type of glaucoma (POAG) was significantly associated with surgical failure (P = 0.044). Furthermore, the surgical success rate was significantly higher in eyes with PEG than it was in those with POAG (P = 0.019). Stand-alone ab interno trabeculotomy significantly lowered both the IOP and the medication score in patients with glaucoma, although almost one quarter of the cases needed additional glaucoma surgeries. The surgical success rate was significantly higher in eyes with PEG than it was in those with POAG.

Bleb leakage is a serious complication of glaucoma filtering surgery. This study describes the method and the results of a new repair method for ischemic bleb leaks. The subjects were consecutive eleven eyes of 11 patients with bleb leakage who underwent the bleb plication surgery. The bleb plication surgery consisted of two steps: 1) bleb needle redirection to float the conjunctiva away from the sclera as extensively as possible around the ischemic conjunctiva; and 2) multiple “O-shaped” sutures were applied between the non-ischemic conjunctiva just outside the ischemic conjunctiva and corneal limbus. The ischemic conjunctiva was not removed, but undermined beneath the advanced non-ischemic conjunctiva. This bleb plication method was repeated until the leakage was sealed. All patients were followed up for at least 6 months after final bleb plication. After final bleb plication, no recurrence of bleb leakage was observed. Moreover, ischemic changes were no longer observed in the advanced non-ischemic conjunctiva. Pre-operative and final intraocular pressure was 3.2 ± 4.1 and 11.9 ± 2.8 mmHg, respectively. This new repair method of bleb plication was safe and effective in sealing the leakage. The conjunctiva is not excised, and hence it does not run out.

To compare 12-month clinical results of spatula-shaped and dual-blade microhooks ab interno trabeculotomy with phacoemulsification. Retrospective comparative study. We conducted a retrospective chart review of Japanese open-angle glaucoma patients who underwent ab interno trabeculotomy with phacoemulsification with a 12-month follow-up. Two types of trabecular hook were used: the spatula-shaped Tanito Trabeculotomy ab interno Micro-hook® and the Kahook Dual Blade®. Changes in intraocular pressure (IOP) and medication scores comprised the main outcome metrics. We also analyzed and compared patient demographics and the occurrence of complications. Trabeculotomy was performed using a spatula-shaped hook in 17 eyes and a dual-blade hook in 15 eyes. Significant reductions in IOP (p

Purpose To investigate the association between different stages of posterior vitreous detachment (PVD) and macular microvasculature in the elderly. Methods Swept-source optical coherence tomography (OCT), OCT angiography, and color fundus images of 490 eyes without retinal pathologies of 322 participants aged ≥65 years were evaluated. PVD was classified using enhanced vitreous visualization mode as no apparent PVD (stage 0/1), vitreous adhesions at the fovea and optic disc (stage 2), adhesion at the optic disc (stage 3), or complete PVD (stage 4). Microvascular parameters, including foveal avascular zone (FAZ) and vessel density (VD), were analyzed for their associations with complete PVD. Additionally, the association between PVD and central retinal thickness (CRT) was also addressed. Results Overall, 80, 31, 31, and 349 eyes were categorized into stages 0/1, 2, 3, and 4, respectively. Using multivariate mixed-effects model, the mean superficial FAZ area was smaller in stage 4 compared with stages 0-3 (0.29 vs. 0.32 mm2; P = 0.014), and the mean superficial VD was lower in stage 4 compared with stages 0-3 (34.96% vs. 35.24%; P = 0.0089). However, PVD was not significantly associated with deep macular microvascular parameters or CRT. Conclusions Complete PVD was associated with smaller FAZ area and lower VD in superficial macular microvasculature, while it was not associated with central retinal thickness.

To evaluate surgeons’ skills and medical devices, interaction between surgical instruments and a physical surgery simulator can be measured by various sensors. This study proposes sensors for a physical surgery model which accurately replicates mechanical properties of human tissues using synthetic materials, and we named such sensors as ”Bionic Sensors”. As an example, we attempted to integrate a sensor measures the force applying to the fundus retina, into an eye surgery simulator, Bionic-EyE™. We designed a cantilever-type load sensor using a quartz crystal resonator (QCR) with a highly load resolution and wide dynamic range and integrated it in the fundus part of Bionic-EyE™ as a Bionic Sensor. The interaction of a microforceps and the fundus part was measured in a simulated task of the inner limiting membrane (ILM) peeling, and the maximum indentation load was approximately 20 mN when the task was performed by a skilled surgeon. The high sensitivity of the bionic sensor designed to measure the millinewton-order indentation force for the ILM peeling task was successfully demonstrated.

Understanding the neural correlates of the neurotic brain is important because neuroticism is a risk factor for the development of psychopathology. We examined the correlation between brain structural networks and neuroticism based on NEO Five-Factor Inventory (NEO-FFI) scores. Fifty-one healthy participants (female, n = 18; male, n = 33; mean age, 38.5 ± 11.7 years) underwent the NEO-FFI test and magnetic resonance imaging (MRI), including diffusion tensor imaging and 3D T1WI. Using MRI data, for each participant, we constructed whole-brain interregional connectivity matrices by deterministic tractography and calculated the graph theoretical network measures, including the characteristic path length, global clustering coefficient, small-worldness, and betweenness centrality (BET) in 83 brain regions from the Desikan-Killiany atlas with subcortical segmentation using FreeSurfer. In relation to the BET, neuroticism score had a negative correlation in the left isthmus cingulate cortex, left superior parietal, left superior temporal, right caudal middle frontal, and right entorhinal cortices, and a positive correlation in the bilateral frontal pole, left caudal anterior cingulate cortex, and left fusiform gyrus. No other measurements showed significant correlations. Our results imply that the brain regions related to neuroticism exist in various regions, and that the neuroticism trait is likely formed as a result of interactions among these regions. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan.

The purpose of this study was to present the novel MRI findings of palatine gland lesion-associated IgG4-related disease (PGL-IgG4-RD) and to compare the imaging features with those in normal individuals. We retrospectively evaluated the MRI scans of 12 patients with PGL-IgG4-RD and 12 control individuals. We measured the thickness of the palatal regions and calculated the T2-weighted signal intensity ratio of palatal regions to cerebral white matter (HWR) and compared them between the PGL-IgG4-RD and control groups. In univariate analysis, the HWR of the palatal regions on T2-weighted imaging was smaller in the PGL-IgG4-RD group than in the control group (average = 1.2 vs. 1.9, p

Purpose To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). Methods Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. Results A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). Conclusion Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. Clinical trial This clinical study was registered in UMIN-CTR (ID: UMIN000042420).

The authors wish to replace the Table 1.

To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT). Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0–3, 4–7, and 8–11 months after WBRT. The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p

Three-dimensional (3D) microfluidic channels, which simulate human tissues such as blood vessels, are useful in surgical simulator models for evaluating surgical devices and training novice surgeons. However, animal models and current artificial models do not sufficiently mimic the anatomical and mechanical properties of human tissues. Therefore, we established a novel fabrication method to fabricate an eye model for use as a surgical simulator. For the glaucoma surgery task, the eye model consists of a sclera with a clear cornea, a 3D microchannel with a width of 200&ndash, 500 &micro, m, representing the Schlemm&rsquo, s canal (SC), and a thin membrane with a thickness of 40&ndash, 132 &micro, m, representing the trabecular meshwork (TM). The sclera model with a clear cornea and SC was fabricated by 3D molding. Blow molding was used to fabricate the TM to cover the inner surface of the sclera part. Soft materials with controllable mechanical behaviors were used to fabricate the sclera and TM parts to mimic the mechanical properties of human tissues. Additionally, to simulate the surgery with constraints similar to those in a real operation, the eye model was installed on a skull platform. Therefore, in this paper, we propose an integration method for fabricating an eye model that has a 3D microchannel representing the SC and a membrane representing the TM, to develop a glaucoma model for training novice surgeons.

To evaluate the potential of full-iterative reconstruction (IR) for improving image quality of the cystic artery on CT angiography and to assess observer performance. Thirty patients who underwent both liver dynamic CT and conventional angiography were included in this retrospective study. All CT data were reconstructed through filtered back projection (FBP), adaptive iterative dose reduction 3D (AIDR3D), and forward-projected, model-based, iterative reconstruction solution (FIRST), respectively. In objective study, we analyzed mean ΔCT numbers (the difference between the HU peak of the vessel and the background) and full-width at tenth-maximum (FWTM) of three parts of the cystic artery by profile curve method comparing the three reconstructions. Subjectively, visualization was evaluated using a four-point scale performed by two blinded observers. ANOVA was used for statistical analysis. In all parts of the cystic artery, the mean ΔCT number of FIRST was shown to be significantly better than that of FBP and AIDR3D (p

Purpose: Compared with healthy subjects (HS), patients with major depressive disorder (MDD) exhibit volume differences that affect the volume changes in several areas such as the limbic, cortical, subcortical, and white matter. Catechol-O-methyltransferase (COMT) is a methylation enzyme that catalyzes endogenous catecholamines. The Val158Met polymorphism of COMT has been reported to affect the dopamine (DA) levels, which plays an important role in psychiatric diseases. However, the relationships among both DA levels, COMT genotype, and brain morphology are complicated and controversial. In previous studies that investigated the hippocampal subfields, the greatest brain abnormalities in MDD patients were observed in Cornu Ammonis (CA)1 and the subiculum, followed by that in CA2-3. We have prospectively demonstrated the relationship between the single-nucleotide polymorphism of the Val158Met COMT gene (rs4680) and the hippocampal subfields in drug-naive MDD patients. Patients and methods: In this study, we compared 27 MDD patients and 42 HS who were divided into groups based on their COMT genotype. The effects of the diagnosis, genotype, and genotype–diagnosis interaction related to CA1 and the subiculum volumes, as well as the whole-brain cortical thickness, were evaluated by performing a FreeSurfer statistical analysis of high-resolution magnetic resonance imaging (MRI) findings. Results: The results revealed that there was a statistically significant interaction between the effects of diagnosis and genotype on the right subiculum (a component of the hippocampus). Conclusion: This Val158Met COMT polymorphism may influence the subiculum volume in drug-naive, first-episode MDD patients.