Lower eyelid position before and after blepharoptosis repair.

PURPOSE: This study aimed to examine the changes in lower eyelid position after blepharoptosis surgery and the factors that influence the outcome. METHODS: We conducted a retrospective study of 155 eyes of 89 patients who underwent blepharoptosis surgery between June 2019 and October 2022. The margin reflex distance (MRD)-1 and MRD-2 were examined preoperatively and 3 months postoperatively in two groups: one with lower scleral show (LSS) (n = 37) and one without LSS (n = 118). The clinical characteristics of the two groups were compared. RESULTS: Both the LSS and non-LSS groups showed significant postoperative improvement in MRD-1 scores (p < .01, p < .01, respectively). MRD-2 was significantly reduced in the LSS group, while it remained unchanged in the non-LSS group (p < .01, p = .27, respectively). There were no significant differences between the two groups in age, sex, history of hard contact lens use, preoperative levator function, use of topical steroids, history of endophthalmic surgery, or history of filtration surgery; however, the LSS group significantly used prostaglandin analogs (PGAs) (p = .03). Postoperatively, MRD-2 decreased in 13 eyes (35.1%) and was maintained in 24 eyes (64.9%) in the LSS group and was maintained in all eyes in the non-LSS group. In the LSS group, we also examined the association between postoperative MRD-2 reduction and the use of PGAs and found that more patients with MRD-2 reduction used PGAs (p = .02). CONCLUSION: Lower scleral show in PGAs-associated blepharoptosis is expected to improve after blepharoptosis surgery.

Comparison of corneal endothelial cell density reduction between primary open-angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery.

PURPOSE: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX). PATIENTS AND METHODS: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test. RESULTS: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy. CONCLUSIONS: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients.

Evaluating the Long-term Stability of a Predefined Palatal Region for Tooth Movement Analysis.

OBJECTIVES: We conducted a three-dimensional (3D) analysis of orthodontic tooth movement (TM) using digital dental models (DMs), focusing on the palatal region of interest (PROI), aiming to evaluate the long-term stability of the PROI, validate the 3D TM analysis with PROI registration, and compare it with conventional lateral cephalometric analyses. METHODS: Twenty adult patients treated with a multibracket appliance were evaluated at their first visit (T0) and at least 5 years later (T1) using DMs and lateral cephalograms (LCs). The long-term stability of PROI was assessed by calculating the point cloud distances between DM-T0 and DM-T1. TM analysis using DM with PROI registration for the maxillary central incisors was assessed through linear and angular measurements in the sagittal view and subsequently compared with the LCs. RESULTS: The average point cloud distance of the PROI between DM-T0 and DM-T1 was 0.21 mm (standard deviation, 0.13 mm). TM analysis using DMs demonstrated excellent reproducibility for both linear and angular measurements (intra-rater correlation coefficient, > 0.99). The 95% limits of agreement between the DM and LC measurements were < 5.14° for angular change, 3.53 mm for vertical displacement, and 0.98 mm for horizontal displacement. No significant differences were observed in the angular and linear measurements when the TM was compared using the DMs and LCs. CONCLUSIONS: The PROI remained stable for over 5 years, supporting the reproducibility and accuracy of TM assessment using PROI registration in orthodontic clinical practice. CLINICAL SIGNIFICANCE: DM analysis lacks the risks associated with X-ray exposure and can be easily performed in daily clinical practice, indicating its potential for future clinical applications. These findings further support the use of DM with PROI registration for TM analysis in orthodontic clinical practice, emphasizing its long-term stability and reproducibility.

Comparative study of surgical outcomes regarding tear meniscus area and high-order aberrations between two different interventional methods for primary acquired nasolacrimal duct obstruction.

PURPOSE: To compare endonasal dacryocystorhinostomy (EN-DCR) with sheath-guided dacryoendoscopic probing and bicanalicular intubation (SG-BCI) by evaluating tear meniscus area (TMA) and total high-order aberrations (HOAs) for primary acquired nasolacrimal duct obstruction (PANDO). METHOD: We retrospectively reviewed 56 eyes of 42 patients (7 men, 35 women; age, 72.7±13.1 years) who underwent EN-DCR or SG-BCI for PANDO in Toyama University Hospital from February 2020 to June 2022. In the EN-DCR and SG-BCI groups, we measured the patency of the lacrimal passage, preoperative and postoperative TMA, and HOAs of the central 4 mm of the cornea using optical coherence tomography (AS-OCT), six months postoperatively. RESULTS: There was a positive correlation between preoperative TMA and preoperative HOAs in all cases. Postoperative patency of lacrimal passage was 100% in the EN-DCR and 80.8% in the SG-BCI group. There was a significant difference in the number of passages between the two groups (p = 0.01). Preoperative TMA and HOAs showed a significant postoperative decrease in both groups (EN-DCR group: p<0.01, p<0.01, SG-BCI group: p<0.01, p=0.03, respectively). We then calculated the rate of change of preoperative and postoperative TMA and HOAs and compared them between the two groups. The rate of change was significantly higher in the EN-DCR group than that in the SG-BCI group (TMA, p=0.03; HOAs, p=0.02). CONCLUSION: Although both EN-DCR and SG-BCI are effective for PANDO, our results suggest that EN-DCR is more effective in improving TMA and HOAs.

Gas Tamponade Improved Cilio-Choroidal Effusion Induced by an Ab Interno Trabeculotomy with a Microhook: Two Cases.

Purpose: We treated two patients with ciliary detachment due to an ab interno trabeculotomy. The ciliary detachment was improved by the use of sulfur hexafluoride (SF6) gas or octafluoro propane (C3F8) tamponade. Patients and Methods: Patient 1 was a 52-year-old Brazilian man with primary open angle glaucoma (POAG). His preoperative intraocular pressure (IOP) was 29 mmHg. Patient 2 was a 57-year-old Japanese woman with POAG. Her preoperative IOP was 35 mmHg. Both patients underwent an ab interno trabeculotomy with a microhook. They caused ciliary detachment as a postoperative complication. We could observe their ciliary detachment with anterior segment optical coherence tomography (AS-OCT). Hypotony persisted for 2 months and the patients' ciliary detachment had not improved. They each underwent a pars plana vitrectomy (PPV) with simultaneous 20% SF6 filling. Results: In Patient 1, the use of the SF6 gas tamponade successfully attached the ciliary body. His IOP was increased to 30 mmHg after this resolution of the ciliary detachment. He underwent additional tube shunt surgery. For Patient 2, the SF6 gas tamponade improved the ciliary detachment but the ciliary body could not be attached. We injected 0.6 cc of 100% C3F8 gas into the vitreous cavity, and this gas tamponade was able to attach the ciliary body. Conclusion: AS-OCT is very useful to evaluate ciliary detachment. PPV+Gas tamponade can be a treatment option for ciliary detachment.

Relationships between fusional convergence, suppression depth, and exotropia control in intermittent exotropia.

Purpose: To assess the correlation between the contribution rates of fusional convergence from the dominant and non-dominant eye and suppression depth and exotropia control. Study design: Cross-sectional prospective study. Methods: The fusional convergence of 25 participants with intermittent exotropia (mean age 10.8 ± 3.4; range 6-18 years) was measured with an eye-tracking system. The contribution rate was defined based on the amplitude of fusional convergence during refusion relative to the exo-deviation angle. The suppression depth was assessed, and exotropia control was evaluated using the intermittent exotropia Office Control Score. We analyzed the correlations between the contribution rate from the dominant and non-dominant eyes and the suppression depth or control score. Results: There was a negative correlation between the dominant eye's contribution rate and the suppression depth in both eyes (r = -0.85, 95% confidence interval [CI]: -0.97 to - 0.20 in the fixated dominant eye and r = -0.91, 95%CI: -0.95 to - 0.40 in the fixated non-dominant eye). There was a negative correlation between the dominant eye's contribution rate and the control score at a 4-meter distance (r = -0.53, 95%CI: -0.76 to - 0.17). Conclusion: Suppression in intermittent exotropia patients could affect the fusional convergence in the dominant eye.

The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorγt+Treg and PD-1 blockade efficacy.

Immune 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 (Rorγt+ 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.

Clostridium butyricum MIYAIRI 588 contributes to the maintenance of intestinal microbiota diversity early after haematopoietic cell transplantation.

In patients undergoing haematopoietic stem-cell transplantation (HSCT), the intestinal microbiota plays an important role in prognosis, transplant outcome, and complications such as graft-versus-host disease (GVHD). Our prior research revealed that patients undergoing HSCT substantially differed from healthy controls. In this retrospective study, we showed that administering Clostridium butyricum MIYAIRI 588 (CBM588) as a live biotherapeutic agent is associated with maintaining intestinal microbiota in the early post-HSCT period. Alpha diversity, which reflects species richness, declined considerably in patients who did not receive CBM588, whereas it remained consistent in those who received CBM588. In addition, ß-diversity analysis revealed that CBM588 did not alter the gut microbiota structure at 7-21 days post-HSCT. Patients who developed GVHD showed structural changes in their microbiota from the pre-transplant period, which was noticeable on day 14 before developing GVHD. Enterococcus was significantly prevalent in patients with GVHD after HSCT, and the population of Bacteroides was maintained from the pre-HSCT period through to the post-HSCT period. Patients who received CBM588 exhibited a contrasting trend, with lower relative abundances of both genera Enterococcus and Bacteroides. These results suggest that preoperative treatment with CBM588 could potentially be beneficial in maintaining intestinal microbiota balance.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

Novel rapid method for identifying and quantifying pathogenic bacteria within four hours of blood collection.

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.

Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.

Changes in saccadic eye movement and smooth pursuit gain in patients with acquired comitant esotropia after strabismus surgery.

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.