GDF5+ chondroprogenitors derived from human pluripotent stem cells preferentially form permanent chondrocytes.

It has been established in the mouse model that during embryogenesis joint cartilage is generated from a specialized progenitor cell type, distinct from that responsible for the formation of growth plate cartilage. We recently found that mesodermal progeny of human pluripotent stem cells gave rise to two types of chondrogenic mesenchymal cells in culture: SOX9+ and GDF5+ cells. The fast-growing SOX9+ cells formed in vitro cartilage that expressed chondrocyte hypertrophy markers and readily underwent mineralization after ectopic transplantation. In contrast, the slowly growing GDF5+ cells derived from SOX9+ cells formed cartilage that tended to express low to undetectable levels of chondrocyte hypertrophy markers, but expressed PRG4, a marker of embryonic articular chondrocytes. The GDF5+-derived cartilage remained largely unmineralized in vivo. Interestingly, chondrocytes derived from the GDF5+ cells seemed to elicit these activities via non-cell-autonomous mechanisms. Genome-wide transcriptomic analyses suggested that GDF5+ cells might contain a teno/ligamento-genic potential, whereas SOX9+ cells resembled neural crest-like progeny-derived chondroprogenitors. Thus, human pluripotent stem cell-derived GDF5+ cells specified to generate permanent-like cartilage seem to emerge coincidentally with the commitment of the SOX9+ progeny to the tendon/ligament lineage.

Aqueous humour protein dysregulation in Asian eyes with primary open angle glaucoma.

The pathophysiology of Primary Open Angle Glaucoma (POAG) remains poorly understood. Through proteomic analysis of aqueous humour (AH) from POAG patients, we aim to identify changes in protein composition of these samples compared to control samples. High resolution mass spectrometry-based TMT6plex quantitative proteomics analysis is performed on AH samples collected from POAG patients, and compared against a control group of patients with cataracts. Data are available via ProteomeXchange with identifier PXD033153. 1589 proteins were quantified from the aqueous samples using Proteome Discoverer version 2.2 software. Among these proteins, 210 were identified as unique master proteins. The proteins which were up or down-regulated by ±3 fold-change were considered significant. Human neuroblastoma full-length cDNA clone CS0DD006YL02 was significantly upregulated in patients with severe POAG on >2 medications, while actin, cytoplasmic 1, V2-7 protein (fragment), immunoglobulin-like polypeptide 1 and phosphatidylethanolamine-binding protein 4 were only present in these patients with severe POAG on >2 medications. Beta-crystallin B1 and B2, Gamma-crystallin C, D and S were significantly downregulated in the severe POAG ≤2 glaucoma medications group. Beta-crystallin B2, Gamma-crystallin D and GCT-A9 light chain variable region (fragment) were significantly downregulated in the non-severe POAG group. Actin, cytoplasmic 1 was significantly upregulated in subjects with severe POAG who required more than 2 glaucoma medications. Crystallins (Beta-crystallin B1 and B2, Gamma-crystallin C, D and S) were significantly downregulated in subjects with severe POAG who required less than 2 glaucoma medications.

Angle-based minimally invasive glaucoma surgery in normal tension glaucoma: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis quantitatively examines the efficacy of angle-based minimally invasive glaucoma surgery (MIGS) in normal tension glaucoma (NTG). METHODS: A literature search was performed on Medline, Embase, PubMed, CINAHL and Cochrane Library from inception until 20 December 2022. Pilot, cohort, observational studies and randomised controlled trials including at least 5 subjects undergoing angle-based MIGS (trabecular-bypass devices, excisional trabeculotomy, goniotomy and ab-interno canaloplasty) for NTG, with or without cataract surgery, were included. Meta-analysis of continuous outcome using the meta routine in R version 2022.12.0+353 was performed to determine mean intraocular pressure (IOP) and anti-glaucoma medication (AGM) reduction post-operatively. RESULTS: Of the 846 studies initially identified, 15 studies with a pooled total of 367 eyes which underwent combined phacoemulsification and angle-based MIGS were included for final meta-analysis. Outcomes of the iStent were reported in 5 studies, iStent inject in 7 studies, Hydrus Microstent in 1 study, Kahook Dual Blade in 3 studies, and Trabectome in 2 studies. There was significant reduction in both IOP and AGM post-operatively at 6 months (2.44 mmHg, 95%CI: 1.83-3.06; 1.21 AGM, 95%CI: 0.99-1.44), 12 months (2.28 mmHg, 95%CI: 1.71-2.84; 1.18 AGM, 95%CI: 0.90-1.47), 24 months (2.10 mmHg, 95%CI: 1.51-2.68; 1.26 AGM, 95%CI: 0.85-1.68) and 36 months (2.43 mmHg, 95%CI: 1.71-3.15, 0.87 AGM, 95%CI: 0.21-1.53) (all p < 0.05). Subgroup analysis on combined phacoemulsification-iStent inject surgery demonstrated a reduction in both IOP (2.31 mmHg, 95%CI: 1.07-3.56, p < 0.001) and AGM (1.07 AGM, 95%CI: 0.86-1.29, p < 0.001) at 12 months post-operatively. CONCLUSIONS: Angle-based MIGS combined with phacoemulsification effectively reduces IOP and AGM in NTG eyes for up to 36 months after surgery.

Preoperative veterans RAND-12 mental composite score of < 35 is associated with increased length of stay and high rates of discharge to rehab after primary total joint arthroplasty.

PURPOSE: The association between preoperative mental health and immediate postoperative ambulation in primary Total Joint Arthroplasty (TJA) has sparsely been studied. Thus, this study's objective was to investigate the association between mental health (measured by the Mental Component Score (MCS) from the Veterans RAND 12 (VR-12)) and peri-operative metrics. METHODS: We conducted a retrospective study of patients who underwent primary TJA and completed a VR-12 questionnaire between January 2018 and June 2023 at a single academic hospital. Patients were stratified into terciles based on preoperative MCS. Patient demographics, ambulation within 4 h postop, LOS, and discharge location were compared. The effect of MCS on LOS while controlling discharge location was assessed using negative binomial regression. RESULTS: 1120 patients were included in this analysis (432 THA and 688 TKA). After stratification into terciles (Low: 34.7 ± 6.6, Middle: 49.3 ± 3.7, High:62.1 ± 4.4), comparison of demographics revealed significant differences in age (p = 0.005) and sex distribution (p = 0.04) but no difference in surgery type (p = 0.857). There was no significant difference in ambulation rate between MCS groups (p = 0.789) or in distance covered during first ambulation (p = 0.251). Low MCS patients had a longer LOS (p = 0.000, p = 0.002) and a lower rate of discharged home (p = 0.016). After controlling discharge location, no significant association was found between MCS and LOS (p = 0.288). CONCLUSION: Patient with low MCS tended to be younger, women, and had poorer preoperative HOOS/KOOS scores. Low MCS was associated with longer LOS and lower rates of discharge home. However, MCS was not associated with early ambulation rate and LOS after controlling discharge location.

Remote Perimetry in a Virtual Reality Metaverse Environment for Out-of-Hospital Functional Eye Screening Compared Against the Gold Standard Humphrey Visual Fields Perimeter: Proof-of-Concept Pilot Study.

BACKGROUND: The growing global burden of visual impairment necessitates better population eye screening for early detection of eye diseases. However, accessibility to testing is often limited and centralized at in-hospital settings. Furthermore, many eye screening programs were disrupted by the COVID-19 pandemic, presenting an urgent need for out-of-hospital solutions. OBJECTIVE: This study investigates the performance of a novel remote perimetry application designed in a virtual reality metaverse environment to enable functional testing in community-based and primary care settings. METHODS: This was a prospective observational study investigating the performance of a novel remote perimetry solution in comparison with the gold standard Humphrey visual field (HVF) perimeter. Subjects received a comprehensive ophthalmologic assessment, HVF perimetry, and remote perimetry testing. The primary outcome measure was the agreement in the classification of overall perimetry result normality by the HVF (Swedish interactive threshold algorithm-fast) and testing with the novel algorithm. Secondary outcome measures included concordance of individual testing points and perimetry topographic maps. RESULTS: We recruited 10 subjects with an average age of 59.6 (range 28-81) years. Of these, 7 (70%) were male and 3 (30%) were female. The agreement in the classification of overall perimetry results was high (9/10, 90%). The pointwise concordance in the automated classification of individual test points was 83.3% (8.2%; range 75%-100%). In addition, there was good perimetry topographic concordance with the HVF in all subjects. CONCLUSIONS: Remote perimetry in a metaverse environment had good concordance with gold standard perimetry using the HVF and could potentially avail functional eye screening in out-of-hospital settings.

12-Month Outcomes of Combined Phacoemulsification and iStent Inject in Asian Eyes with Normal Tension Glaucoma: A Single-Centre Experience.

PURPOSE: To evaluate efficacy and safety of the iStent inject combined with phacoemulsification in Asian eyes with normal-tension glaucoma (NTG) up to 12 months after surgery. STUDY DESIGN: Retrospective case series. METHODS: Retrospective case series of eyes undergoing surgery from April 2017 to August 2019. Outcome measures included intraocular pressure (IOP), number of topical glaucoma medications and adverse outcomes. Data were retrieved from the post-operative day 1 (POD1), week 1 (POW1), month 1 (POM1), month 3 (POM3), month 6 (POM6) and month 12 (POM12) timepoints. Data were analysed at each timepoint for eyes with available clinical data at that visit. Subgroup analysis was performed for a consistent cohort which included only eyes with data at all six follow-up timepoints. RESULTS: Data from 91 eyes in the collective subject group was analysed. Majority of subjects were male (53, 58.2%) and Chinese (79, 86.8%). Mean age was 73.2 ± 7.2 years. Pre-operatively, mean IOP was 14.3 ± 3.0 mmHg and mean number of medications was 1.5 ± 0.8. Significant IOP reduction was observed at all timepoints except POW1 and POM12. The number of medications was reduced at all timepoints (p < 0.001). By POM12, there was reduction of 1.2 ± 1.0 medications (p < 0.001). Both the collective and consistent cohorts demonstrated a trend towards decreasing surgical efficacy with time, in IOP reduction and decrease in medications. None of the eyes experienced sight-threatening complications. CONCLUSIONS: Asian eyes with NTG undergoing combined phacoemulsification and iStent inject surgery demonstrated significant and sustained reduction in number of glaucoma medications up to 12 months post-operatively.

Five-Year Outcomes of Endoscopic Sleeve Gastroplasty for the Treatment of Obesity.

BACKGROUND AND AIMS: The growing burden of obesity as a chronic disease necessitates a multifaceted approach to management. There has been an increase in the number of available endoscopic therapies for weight management with endoscopic sleeve gastroplasty (ESG) proving to be one of the best options. The long-term efficacy of ESG for management of obesity is not known. This study sought to assess the long-term safety and efficacy of ESG for treatment of obesity. METHODS: This was a prospective cohort study. Participants underwent ESG in a single academic center, and were prospectively enrolled. All procedures were performed by the same therapeutic endoscopist. Patients with a body mass index of >30 kg/m2 (or >27 with comorbidities), who underwent ESG from August 2013 to August 2019 for treatment of obesity were enrolled. Patients were followed for up to 5 years after their procedure. The primary outcome was weight loss at 5 years after the procedure (% total body weight loss, TBWL) RESULTS: 216 patients (68% female) with a mean age of 46±13 years, and mean BMI of 39±6 kg/m2 underwent ESG. Out of 216 patients, 203, 96, and 68 patients were eligible for a 1-, 3-, and 5-year follow up, with complete follow-up rates of 70%, 71%, and 82%, respectively. At 5 years, mean TBWL was 15.9% (95% CI, 11.7-20.5, p < .001) and 90 and 61% of patients maintained 5 and 10% TBWL, respectively. There was an overall rate of 1.3% moderate adverse events (AEs), without any severe or fatal AEs. CONCLUSIONS: Our results suggest that ESG is safe and effective for treatment of obesity, with durable long-term results for at least up to 5 years after the procedure. This procedure should be considered as a reliable option for treatment of obesity.

Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG. METHODS: One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis. RESULTS: Patients' mean body mass index was 40 ± 7 kg/m2 at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02). CONCLUSIONS: Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering.

The cartilage of joints, such as meniscus and articular cartilage, is normally long lasting (i.e., permanent). However, once damaged, especially in large animals and humans, joint cartilage is not spontaneously repaired. Compensating the lack of repair activity by supplying cartilage-(re)forming cells, such as chondrocytes or mesenchymal stromal cells, or by transplanting a piece of normal cartilage, has been the basis of therapy for biological restoration of damaged joint cartilage. Unfortunately, current biological therapies face problems on a number of fronts. The joint cartilage is generated de novo from a specialized cell type, termed a 'joint progenitor' or 'interzone cell' during embryogenesis. Therefore, embryonic chondroprogenitors that mimic the property of joint progenitors might be the best type of cell for regenerating joint cartilage in the adult. Pluripotent stem cells (PSCs) are expected to differentiate in culture into any somatic cell type through processes that mimic embryogenesis, making human (h)PSCs a promising source of embryonic chondroprogenitors. The major research goals toward the clinical application of PSCs in joint cartilage regeneration are to (1) efficiently generate lineage-specific chondroprogenitors from hPSCs, (2) expand the chondroprogenitors to the number needed for therapy without loss of their chondrogenic activity, and (3) direct the in vivo or in vitro differentiation of the chondroprogenitors to articular or meniscal (i.e., permanent) chondrocytes rather than growth plate (i.e., transient) chondrocytes. This review is aimed at providing the current state of research toward meeting these goals. We also include our recent achievement of successful generation of "permanent-like" cartilage from long-term expandable, hPSC-derived ectomesenchymal chondroprogenitors.

Standalone XEN45 Gel Stent implantation versus combined XEN45-phacoemulsification in the treatment of open angle glaucoma-a systematic review and meta-analysis.

PURPOSE: The XEN45 Gel Stent is currently the only FDA-approved sub-conjunctival minimally invasive glaucoma surgery (MIGS) procedure. It has been used worldwide either as a standalone implantation procedure or in combination with phacoemulsification surgery. Concomitant phacoemulsification is understood to influence outcomes of traditional subconjunctival filtering surgery. However, the comparative efficacy between standalone XEN45 Gel Sent implantation ("Standalone XEN45") and combined XEN-phacoemulsification surgery ("XEN45-Phaco") remains unclear. This study aims to appraise current literature to compare the efficacy of Standalone XEN45 and XEN45-Phaco in open-angle glaucoma. METHODS: A comprehensive search of PubMed, CINAHL, CENTRAL databases was performed with the terms "Xen surgery" followed by selective vetting. Pilot, cohort, observational studies and randomised controlled trials that included at least 10 patients undergoing either Standalone XEN45 or XEN45-Phaco surgeries for the treatment of open-angle glaucoma were deemed eligible for inclusion after independent assessment by 2 authors. The search workflow was reported according to the PRISMA guidelines. Data was pooled using random-effects model. A meta-analysis of continuous outcome and proportions was performed using the meta routine in R v3.2.1. RESULTS: Ten studies were included. There was a statistically significant difference in IOP reduction favouring Standalone XEN45 at post-operative day 1, week 1, months 1, 3 and 6. There was a statistically significant difference in decrease in IOP-lowering medications favouring Standalone XEN45 at post-operative week 1 and month 1. CONCLUSION: Standalone XEN45 has superior IOP-lowering outcomes compared to XEN45-Phaco in the early post-operative period, up to 6 months after surgery.

The relationship of global sagittal malalignment to fatty infiltration in the aging spine.

PURPOSE: To investigate associations between muscle size, fat infiltration (FI), and global sagittal alignment in patients with adult spinal deformity (ASD). METHODS: Retrospective cohort study was conducted on a single-institution database of ASD patients with preoperative radiographs and CTs. Following multiplanar reconstructions of CTs, images in the plane of each vertebra were generated. The posterior vertebral musculature (PVM) was contoured on axial images at three vertebral levels (T2, T10, L3). FI was calculated by comparing Hounsfield units within muscles to the normative values of fat. Correlation analyses were conducted between demographics, alignment, and muscle characteristics. RESULTS: 107 patients underwent preoperative spine CT (58yo, 79%F, BMI 27 kg/m2). Muscle data were available for 49 pts at T2, 39 pts at T10, and 81 pts at L3. Mean FI was T2 = 33% ± 18, T10 = 28% ± 19, L3_Erector = 39% ± 19, and L3_Psoas = 19% ± 9. FI correlated across levels (T2 vs. T10 r = 0.698; T10 vs L3_Erector r = 0.506; L3_Erector vs Psoas r = 0.419) and with demographics; older pts had greater fat percentages (r = 0.31-0.45) and BMIs (r = 0.24-0.51). Increased FI at T2, T10, and L3 was associated with increased pelvic retroversion (PT: r = 0.25-0.43), global deformity (TPA: r = 0.27-0.45), and anterior malalignment (SVA: r = 0.23-0.41). The degree of FI in the PVM increased with the severity of SRS-Schwab PT and SVA modifiers. CONCLUSION: In ASD patients, global sagittal malalignment is related to FI of the PVM throughout the lumbar and thoracic spine, as identified through CT. Future research should investigate how FI relates to ASD pathogenesis.

Industry Payments and Their Association With Academic Influence in Total Joint Arthroplasty.

BACKGROUND: The relationship between industry payments and academic influence, as measured by the Hirsch index (h-index) and number of publications, among adult reconstruction surgeons is not well characterized. The aims of the present study are to determine the relationship between an adult reconstruction surgeons' academic influence and their relevant industry payments and National Institutes of Health (NIH) funding. METHODS: Adult reconstruction surgeons were identified through the websites for the orthopedic surgery residency programs in the United States during the 2019-2020 academic year. Academic influence was approximated by each physician's h-index and total number of publications. Industry payment data were obtained through the Open Payments Database, and NIH funding was determined through the NIH website. Mann-Whitney U testing and Spearman correlations were performed to examine relevant associations. RESULTS: Surgeons who received industry research payments had a higher mean h-index (16.1 vs 10.2, P < .001) and mean number of publications (79.1 vs 35.9, P < .001) than physicians who received no industry research payments. Surgeons receiving NIH funding had a higher mean h-index (48.1 vs 10.4, P < .001) and mean number of publications (294.5 vs 36.8, P < .001) than surgeons who did not receive NIH funding. There was no association between the average h-index (P = .668) and number of publications (P = .387) among adult reconstruction surgeons receiving industry nonresearch funding. CONCLUSION: h-index and total publications do not seem to be associated with industry nonresearch payments in the field of total joint arthroplasty. Altogether, these data suggest that industry bias may not play a strong role in total joint arthroplasty.

Refractive outcomes, corneal haze and endothelial cell loss after myopic photorefractive keratectomy in an Asian population: The Singapore Armed Forces' experience.

IMPORTANCE: This study reports outcomes of myopic photorefractive keratectomy (PRK) in a mainly ethnic Chinese population in Singapore. BACKGROUND: To assess the incidence and associations of corneal haze and endothelial cell count (ECC) loss up to 12 months after PRK. DESIGN: This was a retrospective case series conducted in a tertiary eye centre. PARTICIPANTS: A total of 158 patients (309 eyes) with a mean age of 22.1 ± 3.4 years were included. The majority was Chinese (97.4%) and male (97.4%). Mean preoperative spherical equivalent was -3.33 ± 1.15 D. METHODS: Eyes were categorized based on postoperative haze severity. A multivariate analysis adjusting for age and use of intraoperative mitomycin-C (MMC), preoperative sphere and cylinder was performed. MAIN OUTCOME MEASURES: Refractive outcomes and corneal haze 3 and 12 months after PRK were assessed. ECC measurements were obtained before PRK and at variable periods postoperatively. RESULTS: At 12 months, overall efficacy index was 0.98, and safety index was 1.09. Eight (2.5%) eyes underwent enhancement surgery. An analysis was performed on 295 eyes that did not undergo enhancement and had complete clinical data, which demonstrated a decrease in the incidence of haze from 38.2% at 3 months to 9.3% at 12 months. Higher myopia was associated with increased haze severity at 3 months (OR, 1.36; P = .005). Higher astigmatism was associated with increased haze severity at 3 (OR, 1.65; P = .018) and 12 months (OR, 2.32; P = .015). Intraoperative MMC was not associated with haze severity or ECC loss. CONCLUSIONS AND RELEVANCE: Myopia and astigmatism were associated with increased corneal haze severity. Intraoperative MMC did not accelerate ECC loss. Overall, PRK is effective, predictable and safe in Asian eyes.

Efficacy of the XEN gel stent on intraocular pressure lowering in East Asian eyes.

PURPOSE: This study aims to evaluate the efficacy and safety of XEN45 gel stent (Allergan plc, Dublin, Ireland) in East Asian patients with glaucoma. METHODS: A retrospective study of consecutive XEN45 gel stent implantation surgeries with or without concurrent cataract surgery from May 2017 to August 2018 was performed in a single institution. The clinical charts of all cases were reviewed to examine the safety and efficacy of the implant. Primary outcome measures were intraocular pressure (IOP), number of topical glaucoma medications required, additional procedures done and adverse outcomes. All patients included were required to fulfil a minimum of three follow-up visits by post-operative month 1. RESULTS: Sixty-three eyes were included in the study. The median duration of follow-up was 6 months [interquartile range (IQR) 2-9]. Median IOP was significantly lowered from 19 mmHg (IQR 16-24) pre-operatively to 15 mmHg (IQR 11-18) at the end-of-follow-up (p < 0.001). The median number of medications was reduced from 3 (IQR 2-4) at baseline to 0 (IQR 0-2) at the end-of-follow-up (p < 0.001). 66.7% of patients were medication-free by the end of follow-up. Post-operative bleb intervention was required for 61.9% of eyes. Adverse events included post-operative hypotony requiring intervention (4.8%) and post-operative gross hyphaema (9.6%). CONCLUSION: The XEN45 gel stent when used as a sole procedure or in combination with cataract surgery in East Asian eyes is effective in the treatment of glaucoma. However, a high rate of post-operative bleb intervention appears to be required to support its efficacy.

Correlation of myopia severity with visual performance.

PURPOSE: To describe visual performance in high myopia. METHODS: In this cross-sectional study, 148 emmetropes [spherical equivalent (SE) - 0.50 to + 1.00 D] and 564 high myopes [SE ≤ - 6.00 D] were categorised into three groups (Group 1: SE - 6.00 to > - 8.00 D; Group 2: SE - 8.00 to > - 10.00 D; and Group 3: SE ≤ - 10.00 D). Multivariate regression analyses adjusting for age and ethnicity examined the relationship between corrected distance visual acuity (CDVA) [photopic, mesopic and super vision test-night vision goggles (SVT-NVG)] and contrast sensitivity (CS)] (mesopic and SVT-NVG) with SE and axial length (AL). RESULTS: Mean age of subjects was 21.07 ± 1.17 years, and majority were Chinese (91.9%). Mean SE was 0.10 ± 0.23 D (emmetropes) and - 8.76 ± 2.04 D (high myopes), p < 0.001. Higher degrees of myopia were associated with reduced CDVA and CS, and increased AL (all p < 0.001). Among high myopes, Group 1 had the highest proportion of subjects with good CDVA (photopic ≤ 0.00 LogMAR, mesopic ≤ 0.00 LogMAR and NVG ≤ 0.10 LogMAR) and CS (mesopic ≥ 0.75 LogCS and NVG ≥ 0.35 LogCS) compared with Groups 2 and 3 (all p < 0.001). Among high myopes with good VA (photopic ≤ 0.00 LogMAR, mesopic ≤ 0.00 LogMAR and NVG ≤ 0.10 LogMAR), Group 1 also had the highest proportion of subjects who achieved mesopic ≥ 0.75 LogCS and NVG ≥ 0.35 LogCS (both p < 0.001). Multivariate analyses demonstrated that reduced VA and CS were associated with decreased SE and increased AL (all p < 0.001). CONCLUSIONS: High myopia is associated with reduced VA and reduced CS.

Proteomic Analysis of Aqueous Humor from Primary Open Angle Glaucoma Patients on Drug Treatment Revealed Altered Complement Activation Cascade.

Primary open angle glaucoma (POAG) is a complex disease and a leading cause of irreversible blindness, and its underlying pathophysiology remains poorly understood. Proteomic characterization of the protein composition of aqueous humor (AH) may identify prognostic candidate proteins involved in pathogenesis and progression of the disease. To delineate the possible mechanisms that lead to POAG, this study adopted state-of-art mass spectrometric technique and analyzed AH of POAG and their respective controls. In total, more than 1000 proteins were identified with false discovery rate of less than 1%. Numerous proteins of complement cascade, immunoglobulin, neuronal and amyloidogenic proteins, which were part of processes like acute-phase and inflammatory response, humoral immune and acute inflammatory response, regulation of complement activation and protein processing were identified. Proteins of complement system underwent significant changes, which correlate to pathogenic events characterizing POAG, including altered complement cascade, astrocyte activation, neural degeneration, and apoptosis. Further, protein modification such as deamidation of complement subcomponent was noted, particularly in POAG. Proteomic analysis of AH allows a better understanding of the mechanism involved in the pathogenesis of POAG.

Changes in Japanese eyes after laser peripheral iridotomy: an anterior segment optical coherence tomography study.

BACKGROUND: The aim was to investigate the changes in anterior segment parameters, as assessed by anterior segment optical coherence tomography in Japanese subjects after laser peripheral iridotomy (LPI). DESIGN: This was a prospective observational study. PARTICIPANTS: The participants include 72 subjects with angle closure including primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG). METHODS: Anterior segment optical coherence tomography parameters was measured by customized software. Complete data of 51 subjects were available for final analysis. MAIN OUTCOME MEASURES: These were the following parameters: angle opening distance, trabecular-iris space area, anterior chamber depth, width, area and volume (iris thickness, curvature, and area, and lens vault (LV). RESULTS: A total of 25 PACS, 17 PAC and 9 PACG were included. Mean age was 74.7 ± 6.7 years, and majority were women (80.4%). Following LPI, there was a significant increase in mean gonioscopic angle width (1.16 vs. 1.93, P < 0.001) and a corresponding increase in angle opening distance, trabecular-iris space area, and angle recess area (all P < 0.001). The anterior chamber area (P < 0.001), anterior chamber volume (P < 0.001) and anterior chamber depth (P = 0.003) increased significantly; and iris curvature (P < 0.001) was significantly reduced. There were no significant changes in anterior chamber width, LV, iris thickness and area. Age-adjusted and gender-adjusted analysis for predictors of percentage change in angle opening distance 750 showed significant association with greater baseline LV (ß = 0.32, P = 0.03). No significant differences were noted in the mean percentage change in parameters between the PACS and PAC-PACG. CONCLUSIONS: An increase in anterior chamber dimensions, angle widening and iris flattening; with a constant LV, iris thickness and iris area after LPI was demonstrated in Japanese eyes with angle closure.

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

Comparison of Peripapillary Choroidal Thickness Between Primary Open-angle Glaucoma, Normal Tension Glaucoma, and Normal Eyes: A Systematic Review and Meta-analysis.

TOPIC: To investigate differences in peripapillary choroidal thickness (PPCT) between primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and healthy eyes, additionally comparing differences between POAG and NTG eyes. CLINICAL RELEVANCE: Peripapillary choroidal thickness is a well-established OCT parameter in eyes with glaucoma and other ocular pathologies. The relationship between PPCT and glaucoma, if better understood, may facilitate the development of PPCT as a potential diagnostic and monitoring metric for glaucoma. In particular, there has yet to be a synthesis that directly compares PPCT between POAG eyes and NTG eyes. METHODS: A comprehensive literature search was performed on PubMed, EMBASE, and Cochrane Library, identifying studies from inception to December 2022. We included studies that measured PPCT using OCT in POAG, NTG, and healthy eyes. Mean difference (MD) among groups was calculated. Statistical analysis was performed using R version 4.2.0. Risk of bias of included studies was assessed using the Newcastle Ottawa Scale (NOS). RESULTS: Eighteen studies were included in this meta-analysis, with a pooled total of 935 healthy control eyes, 446 NTG eyes, and 934 POAG eyes. There was a significant reduction of PPCT in POAG eyes compared with healthy eyes [MD = -16.32; 95% confidence interval (CI) (-27.55 to -5.09)]. Reduction in PPCT was also significant in NTG eyes compared with healthy eyes [MD = -34.96; 95% CI (-49.97 to -19.95)]. NTG eyes had significantly reduced PPCT compared with POAG eyes [MD = -26.64; 95% CI (-49.00 to -4.28)]. CONCLUSIONS: Glaucomatous eyes appear to have significantly reduced PPCT compared with normal healthy eyes. In addition, PPCT in NTG eyes appear significantly thinner compared with that in POAG eyes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Complications Following XEN45 Gel Stent and Glaucoma Drainage Device Implantation During Glaucoma Fellowship.

Purpose XEN45 Gel Stent and glaucoma drainage device (GDD) implantation is safe and effective for glaucoma treatment and should be taught during glaucoma fellowship training. However, complications may still occur, with potentially sight-threatening consequences. The purpose of this study is to describe the management of complications following a series of XEN45 Gel Stent and GDD surgeries performed over the course of glaucoma fellowship training. Methods This is a retrospective case series of XEN45 Gel Stent surgeries performed on 16 eyes and GDD surgeries performed on seven eyes. Patient demographics, disease characteristics, and complications are reviewed. The intra- and postoperative course of five select cases with complications are described in detail. Results The most frequent complications following XEN45 implantation were transient hypotony (10 eyes, 63%), reduced visual acuity (VA) (five eyes, 31%), choroidal effusion (three eyes, 19%), hyphema (two eyes, 13%), and intraocular pressure (IOP) spike (two eyes, 13%). Thirteen eyes (81%) required bleb needling, and three eyes (19%) required XEN45 replacement. Complications following GDD implantation included hypotony (three eyes, 43%), reduced VA (two eyes, 29%), choroidal effusion (two eyes, 29%), IOP spike (two eyes, 29%), implant exposure (two eyes, 29%), and shallow anterior chamber (one eye, 14%). Three eyes (43%) required revision or explantation with a secondary glaucoma surgery. One choroidal effusion following XEN45 surgery and one following GDD surgery were hemorrhagic choroidal effusions requiring surgical drainage. Conclusion Significant and potentially sight-threatening complications may occur following XEN45 Gel Stent and GDD implantation performed over the course of fellowship training. Glaucoma fellows should be ably equipped to recognize, diagnose, and manage these complications both intra- and postoperatively.