PREDICTING VISUAL OUTCOME AFTER SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE USING A NOVEL CONVOLUTIONAL NEURAL NETWORK.

PURPOSE: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making. METHODS: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated. RESULTS: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane. CONCLUSION: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.

FACTORS RELATED TO UNFAVORABLE VISUAL OUTCOME AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY IN PATIENTS WITH GLAUCOMA.

PURPOSE: To evaluate the visual outcomes after idiopathic epiretinal membrane surgery in glaucomatous and nonglaucomatous eyes and factors related to unfavorable outcomes in glaucomatous eyes. METHODS: This was a retrospective cohort study including patients undergoing idiopathic epiretinal membrane surgery with ≥12-month follow-up. Final visual acuity at pseudophakic status was compared among groups of glaucoma, glaucoma suspect, and nonglaucoma and correlated with optical coherence tomography and visual field characteristics in patients with glaucoma. RESULTS: Of the 314 patients enrolled, 31 had glaucoma and 22 were glaucoma suspect. Baseline visual acuity and central foveal thickness were similar across the groups. Most patients had improved/stable visual acuity postoperatively, with a lower proportion of 83.9% with glaucoma than 96.9% and 100% without glaucoma and glaucoma suspect, respectively (P = 0.002). The mean visual acuity did not change in the glaucoma group (from 6/29 to 6/23), but it improved from 6/25 to 6/12 (a gain of 16.7 approxETDRS letters) in nonglaucoma and 6/26 to 6/14 in glaucoma suspect (a gain of 14.0 approxETDRS letters) (both P < 0.001). The change of visual acuity was correlated with preoperative visual field defects (P < 0.001, r2 = 0.554). Patients with glaucoma with more advanced, fixation-threatening defects or temporally located inner nuclear layer microcysts were more likely to have worsened visual acuity. CONCLUSION: Visual field testing is imperative for patients with glaucoma before idiopathic epiretinal membrane surgery for outcome assessment.

Pluripotent Stem Cells in Clinical Cell Transplantation: Focusing on Induced Pluripotent Stem Cell-Derived RPE Cell Therapy in Age-Related Macular Degeneration.

Human pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent valuable cell sources to replace diseased or injured tissues in regenerative medicine. iPSCs exhibit the potential for indefinite self-renewal and differentiation into various cell types and can be reprogrammed from somatic tissue that can be easily obtained, paving the way for cell therapy, regenerative medicine, and personalized medicine. Cell therapies using various iPSC-derived cell types are now evolving rapidly for the treatment of clinical diseases, including Parkinson's disease, hematological diseases, cardiomyopathy, osteoarthritis, and retinal diseases. Since the first interventional clinical trial with autologous iPSC-derived retinal pigment epithelial cells (RPEs) for the treatment of age-related macular degeneration (AMD) was accomplished in Japan, several preclinical trials using iPSC suspensions or monolayers have been launched, or are ongoing or completed. The evolution and generation of human leukocyte antigen (HLA)-universal iPSCs may facilitate the clinical application of iPSC-based therapies. Thus, iPSCs hold great promise in the treatment of multiple retinal diseases. The efficacy and adverse effects of iPSC-based retinal therapies should be carefully assessed in ongoing and further clinical trials.

Determinants of post-mydriatic intraocular pressure in phakic eyes with prevalent angle closure diseases.

PURPOSE: This study aimed to identify acute angle closure (AAC) risk following pharmacologic mydriasis and the factors affecting post-mydriatic intraocular pressure (IOP) in a population with a high prevalence of angle closure disease. METHODS: In total, 460 individuals aged ≥ 72 years were enrolled in this cross-sectional community-based screening program. IOP was measured at baseline and 1 hour after mydriasis. Individuals with post-mydriatic IOP spike > 6 mmHg received indentation gonioscopy and IOP-lowering medication. Linear regression analysis was used to identify ocular parameters associated with post-mydriatic IOP elevation. RESULTS: The mean age of participants was 77.8 ± 4.1 years, and 65.4% of them were men. In total, 21 eyes of 16 participants (3.48%) had post-mydriatic IOP spikes (range: 6-13.7 mmHg); among them, 15 eyes had an IOP of > 21 mmHg. None of the participants developed AAC. All eyes with IOP spikes were phakic, except for one with pseudophakic angle closure. Analysis of 381 participants with at least one phakic eye revealed that higher post-mydriatic IOP and IOP changes were associated with narrower angle grading, more extensive peripheral anterior synechiae, shallower central anterior chamber, and thicker lens. According to multiple linear regression analysis, post-mydriatic IOP was independently associated with baseline IOP and factors suggestive of crowded anterior chamber based on gonioscopic findings and central or peripheral anterior chamber depth evaluation in conjunction with lens thickness. CONCLUSION: Post-mydriatic IOP should be measured in phakic eyes with a crowded anterior chamber. Post-mydriatic IOP spikes can be effectively blunted with intervention to prevent AAC.

Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment.

Elevated intraocular pressure (IOP) in glaucoma is due to impairment of aqueous humor drainage via the uveoscleral or trabecular outflow pathway. Latanoprost reduces IOP by increasing the uveoscleral outflow. Despite its potency, long-term daily application of it may cause undesirable side effects and many require more than one medication for IOP control. Recent studies have suggested that oxidative stress in the trabecular meshwork (TM) play an important role in the pathogenesis of impaired trabecular outflow facility. Curcumin, a natural phenolic compound, possesses anti-oxidant and anti-inflammation properties. In this study, we developed a thermosensitive hydrogel containing latanoprost and curcumin-loaded nanoparticles (CUR-NPs), and evaluated its possible therapeutic effects with cultured human TM cells under oxidative stress. The results demonstrated that 20 µM of CUR-NPs might be the optimal concentration to treat TM cells without causing cytotoxicity. Using the newly developed system, both latanoprost and CUR-NPs displayed a sustained-release profile. Treatment with this hydrogel containing CUR-NPs effectively decreased the oxidative stress-mediated damage in TM cells via decreasing inflammation-related gene expression, mitochondrial reactive oxygen stress (ROS) production and apoptosis level. The in vivo biocompatibility revealed no signs of inflammation or damage after topical application of developed hydrogel in rabbits. These results suggest that this dual-drug delivery system might enhance both trabecular and uveoscleral outflow and is promising to develop into a novel treatment for glaucoma.

Diagnostic ability of macular ganglion cell asymmetry in Preperimetric Glaucoma.

BACKGROUND: To evaluate the diagnostic ability of macular ganglion cell asymmetry to diagnose preperimetric glaucoma (PPG), using Cirrus spectral domain optical coherence tomography (OCT). METHODS: This prospective study included 67 eyes of 67 patients with PPG and 67 eyes of 67 age- and refractive error-matched controls. We measured circumpapillary RNFL (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head (ONH) parameters using OCT. Macular ganglion cell asymmetries were expressed as absolute difference and ratios between inferior hemisphere and superior hemisphere, inferotemporal (IT) and superotemporal (ST), IT and superonasal (SN), IT and inferonasal (IN), ST and IN as well as temporal and nasal. An asymmetry index was assigned by taking the absolute value of log10 of the ratio. The area under the receiver operating characteristics curve (AUROC), partial AUROC (pAUROC) ≥ specificities 90 and 95%, cutoff values and sensitivities at specificities 90 and 95% was analyzed. RESULTS: Parameters with largest AUROCs were IT GCIPL thickness (0.784), average RNFL thickness (0.767), and average C/D (0.746). For macular asymmetry parameters, log IT/SN index had the largest AUROC (0.734), followed by log IT/IN index (0.725), and absolute difference of IT-SN GCIPL thickness (0.715). Performance was comparable between the best measures of asymmetry analysis (log IT/SN index) and those of cpRNFL, GCIPL, and ONH parameters (all P > 0.05). The IT/SN asymmetry index not only had the largest pAUROC based on the pAUROCs ≥90 and 95% specificity (0.044 and 0.019) but also had the highest diagnostic sensitivity at 90 and 95% specificities (52.2 and 46.3%). CONCLUSIONS: GCIPL asymmetry measurements have diagnostic ability comparable to cpRNFL, GCIPL, and ONH analysis for PPG. The best macular ganglion cell asymmetry parameter was IT/SN asymmetry index, which could be a new parameter to detect early structural changes in PPG.

Haploinsufficiency of RCBTB1 is associated with Coats disease and familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two heterozygous frameshift mutations in RCBTB1 from three Taiwanese cases through exome sequencing. In patient-derived lymphoblastoid cell lines (LCLs), the protein level of RCBTB1 is approximately half that of unaffected control LCLs, which is indicative of a haploinsufficiency mechanism. By employing transient transfection and reporter assays for the transcriptional activity of ß-catenin, we demonstrated that RCBTB1 participates in the Norrin/FZD4 signaling pathway and that knockdown of RCBTB1 by shRNA significantly reduced nuclear accumulation of ß-catenin under Norrin and Wnt3a treatments. Furthermore, transgenic fli1:EGFP zebrafish with rcbtb1 knockdown exhibited anomalies in intersegmental and intraocular vessels. These results strongly support that reduced RCBTB1 expression may lead to defects in angiogenesis through the Norrin-dependent Wnt pathway, and that RCBTB1 is a putative genetic cause of vitreoretinopathies.

Somatosensory gating is altered and associated with migraine chronification: A magnetoencephalographic study.

Background Brain excitability is changed in migraine but not fully characterized yet. This study explored if somatosensory gating is altered in migraine and linked to migraine chronification. Methods Paired electrical stimuli were delivered to the left index fingers of 21 patients with migraine without aura (MO), 22 patients with chronic migraine (CM), and 36 controls. The first and second responses to the paired stimuli were obtained from the contralateral primary (cSI), contralateral secondary (cSII) and ipsilateral secondary (iSII) somatosensory cortices to compute the gating ratios (second vs. first response strengths). Results The first and second cSI responses and gating ratios differed in all groups ( p < 0.05); the responses were typically smaller in the MO and CM groups. The cSI gating ratio increased as a continuum across controls (0.73 ± 0.04, p < 0.001), MO (0.83 ± 0.04) to CM (0.97 ± 0.06) and was higher in CM vs. controls ( p < 0.001). When MO and CM were combined, cSI gating ratio was associated with headache frequency (r = 0.418, p = 0.005). Paired responses and gating ratios of cSII and iSII did not differ among the groups. Conclusions Somatosensory gating is altered in migraine and associated with headache chronification. Further studies must clarify if this abnormal sensory modulation is a true gating deficit independent of low preexcitation level.

Altered insula-default mode network connectivity in fibromyalgia: a resting-state magnetoencephalographic study.

BACKGROUND: Fibromyalgia (FM) is a disabling chronic pain syndrome with unknown pathophysiology. Functional magnetic resonance imaging studies on FM have suggested altered brain connectivity between the insula and the default mode network (DMN). However, this connectivity change has not been characterized through direct neural signals for exploring the embedded spectrotemporal features and the pertinent clinical relevance. METHODS: We recorded the resting-state magnetoencephalographic activities of 28 patients with FM and 28 age- and sex-matched controls, and analyzed the source-based functional connectivity between the insula and the DMN at 1-40 Hz by using the minimum norm estimates and imaginary coherence methods. We also measured the connectivity between the DMN and the primary visual (V1) and somatosensory (S1) cortices as intrapatient negative controls. Connectivity measurement was further correlated with the clinical parameters of FM. RESULTS: Compared with the controls, patients with FM reported more tender points (15.2±2.0 vs. 5.9±3.7) and higher total tenderness score (TTS; 29.1±7.0 vs. 7.7±5.5; both p < 0.001); they also had decreased insula-DMN connectivity at the theta band (4-8 Hz; left, p = 0.007; right, p = 0.035), but displayed unchanged V1-DMN and S1-DMN connectivity (p > 0.05). When patients with FM and the controls were combined together, the insula-DMN theta connectivity was negatively correlated with the number of tender points (left insula, r = -0.428, p = 0.001; right insula, r = -0.4, p = 0.002) and TTS score (left insula, r = -0.429, p = 0.001; right insula, r = -0.389, p = 0.003). Furthermore, in patients with FM, the right insula-DMN connectivity at the beta band (13-25 Hz) was negatively correlated with the number of tender points (r = -0.532, p = 0.004) and TTS (r = -0.428, p = 0.023), and the bilateral insula-DMN connectivity at the delta band (1-4 Hz) was negatively correlated with FM Symptom Severity (left: r = -0.423, p = 0.025; right: r = -0.437, p = 0.020) and functional disability (Fibromyalgia Impact Questionnaire; left: r = -0.415, p = 0.028; right: r = -0.374, p = 0.050). CONCLUSIONS: We confirmed the frequency-specific reorganization of the insula-DMN connectivity in FM. The clinical relevance of this connectivity change may warrant future studies to elucidate its causal relationship and potential as a neurological signature for FM.

Anti-apoptotic and autophagic effect: Using conditioned medium from human bone marrow mesenchymal stem cells to treat human trabecular meshwork cells.

Introduction: Glaucoma is a vision-threatening disease associated with accelerated aging of trabecular meshwork (TM) which results in elevated intraocular pressure (IOP). Increased oxidative stress in TM plays an important role in cellular molecular damage which leads to senescence. Autophagy is an intracellular lysosomal degradation process which is activated when cells are under stressful condition, and emerging studies have demonstrated increased expression of modulators of apoptosis and expression of autophagic cascade in ex-vivo TM specimens or cultured TM cells under oxidative stress. Recently, studies have shown neuroprotective and IOP-lowering effects after transplanting mesenchymal stem cells (MSCs) or injecting condition medium (CM) of MSCs into ocular hypertension animal models. However, knowledge of the underlying mechanism accounting for these effects is limited. Using condition medium (CM) from human bone marrow-derived mesenchymal stem cells (BM-MSCs), we investigated the effects of the CM derived from BM-MSCs on TM autophagy and apoptosis. Methods: H2O2 was added to culture medium of human TM cells to mimic oxidative damage in glaucomatous eyes, and the autophagic and anti-apoptotic effects of BM-MSCs-derived CM was explored on the oxidatively damaged cells. Mitochondrial ROS production was examined by MitoSOX™, apoptosis was evaluated using terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) staining, and the expression of proteins involved in autophagy as well as extracellular matrix was investigated via Western blot. Results: There were no significant differences in TM cell viability when the cells were treated with different concentrations of CM in the absence of oxidative stress. Cell viability was significantly higher in oxidatively damaged TM cells treated with 1X or 5X CM compared to untreated TM cells under oxidative stress. The mitochondrial ROS level significantly increased with oxidative stress, which was mitigated in the CM treatment groups. DNA fragmentation significantly decreased in oxidatively stressed TM cells after treatment with CM. LCB3 II/LCB3 I was significantly elevated in the oxidative stress group compared to the control group and was significantly decreased in the CM treatment groups. Expression of fibronectin was not significantly different among the groups. Conclusion: The CM derived from human BM-MSCs has the capacity to rescue oxidatively damaged human TM cells associated with decreased autophagy and apoptosis. The BM-MSCs CM has potential for slowing down age- and disease-related degeneration of TM in patients with glaucoma, facilitating success in the control of IOP.

Visual cortex excitability and plasticity associated with remission from chronic to episodic migraine.

OBJECTIVE: Previous magnetoencephalographic (MEG) studies showed different P100m (where 'm' denotes the magnetic counterpart of P100 in conventional visual evoked potentials) responses between episodic migraine (EM) and chronic migraine (CM) interictally. This study investigated the changes of visual P100m in CM patients who remitted to EM from CM after treatment. METHODS: At baseline, 25 patients with CM were studied interictally. For each patient, 30 sequential blocks of 50 P100m responses were obtained by MEG. Sub-averaged amplitudes at blocks 2, 9, 16, 23 and 30 were further compared with that at block 1 to assess response habituation or potentiation (i.e. significant decrease or increase at either block vs block 1). The same study was repeated in those patients who remitted from CM to EM after topiramate treatment. RESULTS: In total, 10 CM patients remitted to EM after treatment. In the follow-up study of these patients during the interictal stage, the P100m at block 1 decreased in amplitude from 53.6 ± 6.6 nAm before remission to 43.0 ± 5.1 nAm (p = 0.028), and the responses at subsequent blocks switched from habituation (amplitude block 30 < block 1 before remission, p = 0.011) to potentiation (block 2 > block 1, p = 0.028). CONCLUSION: The pattern of P100m responses to consecutive stimulation changes with the transition from CM to EM. Visual cortex plasticity might be a potential biomarker reflecting clinical remission of CM.

Sustained visual cortex hyperexcitability in migraine with persistent visual aura.

Persistent aura without infarction, a rare migraine disorder, is defined by aura symptoms that persist for >1 week without radiological evidence of cerebral infarction. To unveil its pathophysiological mechanisms, this study used magnetoencephalography to characterize the visual cortex excitability in persistent aura by comparison with episodic and chronic migraine. We recruited six patients with persistent visual aura, 39 patients with episodic migraine [12 in ictal phase; 27 in interictal phase (with aura, n = 9; without aura, n = 18)], 18 patients with chronic migraine and 24 healthy controls. Five sequential blocks of 50 neuromagnetic prominent 100 ms responses were obtained, and the dynamic change in visual cortex excitability was evaluated by the percentage changes of individual mean prominent 100 ms amplitudes at blocks 2-5 compared with block 1, with a significant increase indicating potentiation. We found that in patients with persistent aura, there was significant potentiation during ictal periods (P = 0.009 and 0.006 at blocks 2 and 5, respectively), and the excitability change was inversely correlated with the duration of aura persistence (correlation coefficient -0.812, P = 0.050, block 2). The interictal recordings (n = 3) also showed potentiation. In terms of the other migraine spectrum disorders, persistent aura differed from episodic migraine in the presence of ictal potentiation. Persistent aura further differed from chronic migraine in the absence of interictal potentiation in chronic migraine. There was a higher percentage change of response amplitude at the end of stimulation (block 5) in persistent aura (43.3 ± 11.7) than in chronic migraine (-7.6 ± 5.5, P = 0.006) and ictal recordings of episodic migraine (-4.9 ± 9.6, P = 0.020). Normal control subjects had no significant response changes. This magnetoencephalographic study showed that the visual cortex in patients with persistent visual aura maintains a steady-state hyperexcitability without significant dynamic modulation. The excitability characteristic supports persistent visual aura as a nosological entity in migraine spectrum disorders and suggests a pathophysiological link to sustained excitatory effects possibly related to reverberating cortical spreading depression.

Optical coherence tomography-guided early postoperative management of XEN Gel implant.

This interventional case series demonstrates the usefulness of anterior segment optical coherence tomography (AS-OCT) in guiding early postoperative management following XEN45 Gel Stent implantation, in conjunction with intraocular pressure (IOP) readings and slit lamp findings. Three primary open-angle glaucoma patients undergoing XEN45 Gel Stent implantation were included. Two patients received early postoperative needling because the IOP was not low enough and AS-OCT revealed that the XEN stent orifice was trapped by the Tenon's capsule. Immediately after needling, the distal tip of the XEN stent was freed and connected to a cystic space with significant IOP reduction. The third patient suffered from abrupt bleb flattening on the 5th postoperative day following XEN stent implantation. AS-OCT revealed internal occlusion of the XEN stent with exudative material, which resolved spontaneously after intensifying topical steroids with improved bleb functioning 2 days later. AS-OCT provides in-depth microscopic evaluation of the XEN stent and its relationship with surrounding tissue. This information is helpful in identifying causes of impaired outflow, determining the timing, and effect of needling intervention in eyes with inadequate bleb functioning or IOP control, especially during the early postoperative period.

Development of topical chitosan/ ß-glycerophosphate-based hydrogel loaded with levofloxacin in the treatment of keratitis: An ex-vivo study.

Staphylococcus species are responsible for most cases of post-operative endophthalmitis. Topical ocular drug was applied for post-operative infection prevention, but the way of delivery encounters many challenges in terms of patient's compliance, drug efficacy, and drug penetration. We used the levofloxacin-loaded chitosan/gelatin/ß-glycerophosphate hydrogel sustained releasing system with good in vitro anti-bacterial efficacy and biocompatibility, which we had previously designed, for ex vivo keratitis model to test the preclinical drug efficacy and to determine drug level in the anterior chamber of the eye. The result showed that the ex-vivo corneal keratitis model with S. aureus infection revealed mild opacity over the central cornea with stromal infiltrate, but without obvious stromal infiltration post levofloxacin-loaded hydrogel treatment after 24 h of infection. Quantification of viable bacteria showed a significant anti-bacterial activity. The histological evidence also showed no visible S. aureus after levofloxacin-loaded hydrogel treatment, with a significant anti-inflammatory effect. We also examined the drug concentration in the aqueous humor 24 h after instilling one drop of the levofloxacin-loaded hydrogel. The concentration achieved to a desired drug level. These results suggested that by the ex-vivo model, levofloxacin-loaded hydrogel can be applied for treatment in post-operative endophthalmitis or keratitis after the ophthalmic surgery.

Outcomes and risk factors for failure after trabeculectomy in Taiwanese patients: medical chart reviews from 2006 to 2017.

AIMS: To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients. METHODS: We reviewed medical records of patients with glaucoma undergoing IT during December 2006-December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively. RESULTS: We enrolled 190 patients (237 eyes; mean age: 54.0±15.3 years; mean postoperative follow-up period: 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications. CONCLUSION: Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.

Pseudophakic pupillary block after phacoemulsification and posterior chamber intraocular lens implantation: Cause identification and treatment refinement.

BACKGROUND: Pseudophakic pupillary block (PPB) was rare in patients who undergo phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Laser peripheral iridotomy was the most reported but ineffective treatment in the literature. METHODS: Retrospective, interventional case series of patients who developed PPB in Taipei Veterans General Hospital from 2017 to 2021. Clinical course, diagnostic methods, treatment and outcomes were recorded and discussed. RESULTS: Four eyes of three patients were documented. All of them had diabetes and diabetic retinopathy. Anterior segment Optical coherence tomography (OCT) of these patients showed an exudative membrane at the peripapillary area while slit lamp image could not provide a clear view due to the severely edematous corneal condition. Laser peripheral iridotomy and yttrium aluminum garnet (YAG) laser aiming to the peripapillary exudation were applied to break the PPB successfully. CONCLUSION: Diabetes mellitus, intravitreal injection and inflammation are crucial risk factors for PPB. Anterior segment OCT can be a useful diagnostic tool for the detection of the peripapillary exudative membrane while corneal clarity is compromised due to high intraocular pressure. In addition to peripheral laser iridotomy, an effective approach to resolve PPB may be the use of the YAG laser to break the exudative membrane.

Widen the Applicability of a Convolutional Neural-Network-Assisted Glaucoma Detection Algorithm of Limited Training Images across Different Datasets.

Automated glaucoma detection using deep learning may increase the diagnostic rate of glaucoma to prevent blindness, but generalizable models are currently unavailable despite the use of huge training datasets. This study aims to evaluate the performance of a convolutional neural network (CNN) classifier trained with a limited number of high-quality fundus images in detecting glaucoma and methods to improve its performance across different datasets. A CNN classifier was constructed using EfficientNet B3 and 944 images collected from one medical center (core model) and externally validated using three datasets. The performance of the core model was compared with (1) the integrated model constructed by using all training images from the four datasets and (2) the dataset-specific model built by fine-tuning the core model with training images from the external datasets. The diagnostic accuracy of the core model was 95.62% but dropped to ranges of 52.5-80.0% on the external datasets. Dataset-specific models exhibited superior diagnostic performance on the external datasets compared to other models, with a diagnostic accuracy of 87.50-92.5%. The findings suggest that dataset-specific tuning of the core CNN classifier effectively improves its applicability across different datasets when increasing training images fails to achieve generalization.

Bleb-related infection after primary trabeculectomy: medical chart reviews from 1993 to 2021.

BACKGROUND: To investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy. METHODS: We reviewed the medical charts of consecutive patients who had received primary trabeculectomy in Taipei Veterans General Hospital. We recorded the demographic and clinical characteristics of patients before, during and after surgery. Furthermore, we recorded the time interval between surgery and infection onset, clinical manifestations and visual outcomes of patients with BRI. The cumulative incidence of BRI was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to explore factors associated with BRI. RESULTS: In total, 1663 eyes were postoperatively followed up for 94.57±65.23 months. The cumulative incidence of BRI was 1.86 per 1000 person-years during the 28-year follow-up period: 24 (1.44%) patients developed BRI and 6 (0.36%) patients additionally developed endophthalmitis. A multivariate analysis revealed a significant association of BRI with wound manipulation, high myopia and hyperlipidaemia. Patients younger than 60 years were more likely to receive wound manipulation than their elderly counterparts (<0.001). One year after BRI, the best corrected visual acuity of the eyes with blebitis did not change significantly, whereas that of the eyes with endophthalmitis worsened significantly. CONCLUSION: Risk factors for BRI after trabeculectomy include wound manipulation, high myopia and hyperlipidaemia. Considering myopia is highly prevalent throughout the world and is a risk factor for glaucoma, the lifelong risk of BRI after trabeculectomy in eyes with high myopia warrants the attention of ophthalmologists.

Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/ thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study.

Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cataract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) ophthalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanoparticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index ~0.045), nanosize (~154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 µg/mL and 50 µg/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 °C within 63 s. The osmolarity of PAgel-LNPs was 301.2 ± 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profile for 7 days. Post-treatment of PAgel-LNPs in TNF-α-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-α, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These results suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE.

Salivary cortisol is associated with cognitive changes in patients with fibromyalgia.

Fibromyalgia (FM) is a stress-related chronic pain disorder with common cognitive complaints. This study characterized cognitive dysfunction in patients with FM and explored whether these changes are linked to altered cortisol levels. Consecutive 44 patients with FM and 48 healthy controls were enrolled for the assessments of subjective and objective cognitive functions and diurnal levels of salivary cortisol (sampled at awakening, 30 min after awakening, 3 pm, and bedtime). All measurements were compared between the groups and evaluated for clinical correlation. The FM group had more subjective cognitive complaints and performed poorer in objective cognitive testing in memory (delayed recall in Chinese Version Verbal Learning Test and Taylor Complex Figure Test), language (Boston Naming Test), and executive domains (Wisconsin Card Sorting Test) after adjustments for education. The diurnal cortisol levels of patients with FM tended to be lower, especially at 30 min after awakening and bedtime. Moreover, moderate positive correlations existed between the Chinese Version Verbal Learning Test, Boston Naming Test and the morning cortisol levels within the FM group. We suggested the altered cognitive function in FM may be linked to stress maladaptation. Future studies are warranted to elucidate whether stress management improves cognitive performance in patients with FM.