Multiplex Imaging for Cell Phenotyping of Early Human Atherosclerosis.

BACKGROUND: Previous studies using animal models and cultured cells suggest that vascular smooth muscle cells (SMCs) and inflammatory cytokines are important players in atherogenesis. Validating these findings in human disease is critical to designing therapeutics that target these components. Multiplex imaging is a powerful tool for characterizing cell phenotypes and microenvironments using biobanked human tissue sections. However, this technology has not been applied to human atherosclerotic lesions and needs to first be customized and validated. METHODS AND RESULTS: For validation, we created an 8-plex imaging panel to distinguish foam cells from SMC and leukocyte origins on tissue sections of early human atherosclerotic lesions (n=9). The spatial distribution and characteristics of these foam cells were further analyzed to test the association between SMC phenotypes and inflammation. Consistent with previous reports using human lesions, multiplex imaging showed that foam cells of SMC origin outnumbered those of leukocyte origin and were enriched in the deep intima, where the lipids accumulate in early atherogenesis. This new technology also found that apoptosis or the expression of pro-inflammatory cytokines were not more associated with foam cells than with nonfoam cells in early human lesions. More CD68+ SMCs were present among SMCs that highly expressed interleukin-1ß. Highly inflamed SMCs showed a trend of increased apoptosis, whereas leukocytes expressing similar levels of cytokines were enriched in regions of extracellular matrix remodeling. CONCLUSIONS: The multiplex imaging method can be applied to biobanked human tissue sections to enable proof-of-concept studies and validate theories based on animal models and cultured cells.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Trocar blade-assisted skewer technique for phacoemulsification of a dislocated lens.

A posteriorly dislocated lens is often managed with a fragmatome through a pars plana approach because it is difficult to manage anteriorly. The lens often sinks to the surface of the retina or floats around in the vitreous cavity during pars plana lensectomy. Mechanical trauma can occur while removing the dislocated lens fragments. However, sometimes the lens can be confined to the anterior vitreous cavity even though the zonules are completely disrupted. It would be ideal if there was a simple way to stabilize and support the lens so that the lens could remain in the posterior chamber while phacoemulsification is performed through a corneal incision as usual. We describe a technique using a trocar blade to stabilize the lens while performing phacoemulsification through a corneal incision. We found it to be a useful and safe instrument to support the subluxated lens during phacoemulsification.

Validation of Diagnostic Codes to Identify Glaucoma in Taiwan's Claims Data: A Multi-Institutional Study.

Background: Healthcare databases play a crucial role in improving our understanding of glaucoma epidemiology, which is the leading cause of irreversible blindness globally. However, the accuracy of diagnostic codes used in these databases to detect glaucoma is still uncertain. Aim: To assess the accuracy of ICD-9-CM and ICD-10-CM codes in identifying patients with glaucoma, including two distinct subtypes, primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: We analyzed electronic medical records data from a 2% random sample of patients who newly underwent visual field examination in Taiwan's largest multi-institutional healthcare system from 2011 to 2020. The diagnosis of glaucoma was confirmed by two ophthalmologists, based on the glaucoma diagnostic criteria. The positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for ICD-9-CM codes 365.1X and 365.2X, and ICD-10-CM codes H4010X, H4011X, H4012X, H4020X, H4021X, H4022X, H4023X and H4024X for glaucoma were calculated. Results: We randomly selected 821 patients (mean age: 56.9 years old; female: 50.5%) from the original cohort of 41,050 newly receiving visual field examination in the study. Among 464 cases with an ICD-9-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 86.5, 96.5, 91.9, and 90.9%, respectively. Among 357 cases with an ICD-10-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 87.0, 92.8, 92.2 and 87.9%, respectively. The accuracy of diagnostic codes to identify POAG and PACG remained consistent. Conclusion: The diagnostic codes were highly reliable for identifying cases of glaucoma in Taiwan's routine healthcare practice. These results provide confidence when using ICD-9-CM and ICD-10-CM codes to define glaucoma cases in healthcare database research in Taiwan.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

RETRACTED: Lai et al. MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling. Cancers 2021, 13, 940.

The Cancers Editorial Office retracts the article, "MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling" [...].

Exploration of agr types, virulence-associated genes, and biofilm formation ability in Staphylococcus aureus isolates from hemodialysis patients with vascular access infections.

Introduction: Staphylococcus aureus, is a pathogen commonly encountered in both community and hospital settings. Patients receiving hemodialysis treatment face an elevated risk of vascular access infections (VAIs) particularly Staphylococcus aureus, infection. This heightened risk is attributed to the characteristics of Staphylococcus aureus, , enabling it to adhere to suitable surfaces and form biofilms, thereby rendering it resistant to external interventions and complicating treatment efforts. Methods: Therefore this study utilized PCR and microtiter dish biofilm formation assay to determine the difference in the virulence genes and biofilm formation among in our study collected of 103 Staphylococcus aureus, isolates from hemodialysis patients utilizing arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs) during November 2013 to December 2021. Results: Our findings revealed that both MRSA and MSSA isolates exhibited strong biofilm production capabilities. Additionally, we confirmed the presence of agr types and virulence genes through PCR analysis. The majority of the collected isolates were identified as agr type I. However, agr type II isolates displayed a higher average number of virulence genes, with MRSA isolates exhibiting a variety of virulence genes. Notably, combinations of biofilm-associated genes, such as eno-clfA-clfB-fib-icaA-icaD and eno-clfA-clfB-fib-fnbB-icaA-icaD, were prevalent among Staphylococcus aureus, isolates obtained from vascular access infections. Discussion: These insights contribute to a better understanding of the molecular characteristics associated with Staphylococcus aureus, infections in hemodialysis patients and provided more targeted and effective treatment approaches.

A comparative study of stereopsis in term and preterm children with and without retinopathy of prematurity.

PURPOSE: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. METHODS: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. RESULTS: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. CONCLUSIONS: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity.

Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice.

Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10-30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Detection of Genomic Structural Variations Associated with Drug Sensitivity and Resistance in Acute Leukemia.

Acute leukemia is a particularly problematic collection of hematological cancers, and, while somewhat rare, the survival rate of patients is typically abysmal without bone marrow transplantation. Furthermore, traditional chemotherapies used as standard-of-care for patients cause significant side effects. Understanding the evolution of leukemia to identify novel targets and, therefore, drug treatment regimens is a significant medical need. Genomic rearrangements and other structural variations (SVs) have long been known to be causative and pathogenic in multiple types of cancer, including leukemia. These SVs may be involved in cancer initiation, progression, clonal evolution, and drug resistance, and a better understanding of SVs from individual patients may help guide therapeutic options. Here, we show the utilization of optical genome mapping (OGM) to detect known and novel SVs in the samples of patients with leukemia. Importantly, this technology provides an unprecedented level of granularity and quantitation unavailable to other current techniques and allows for the unbiased detection of novel SVs, which may be relevant to disease pathogenesis and/or drug resistance. Coupled with the chemosensitivities of these samples to FDA-approved oncology drugs, we show how an impartial integrative analysis of these diverse datasets can be used to associate the detected genomic rearrangements with multiple drug sensitivity profiles. Indeed, an insertion in the gene MUSK is shown to be associated with increased sensitivity to the clinically relevant agent Idarubicin, while partial tandem duplication events in the KMT2A gene are related to the efficacy of another frontline treatment, Cytarabine.

Longitudinal changes in optical coherence tomography angiography characteristics in normal-tension glaucoma with or without high myopia.

PURPOSE: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters. METHODS: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL. RESULTS: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non-highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD. CONCLUSION: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure-function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes.

Real-world effectiveness of intravitreal dexamethasone implants - Comparison between eyes eligible and ineligible for clinical trials and their associated outcomes.

BACKGROUND: Concerns about the generalizability of pivotal randomized controlled trials (pRCTs) findings have been raised. We aimed to compare intravitreal dexamethasone implants' (IDIs) effectiveness for diabetic macular edema (DME) and central retinal vein occlusion (CRVO), between eyes eligible and ineligible for pRCTs. METHODS: This retrospective cohort study analyzed Taiwan's Chang Gung Research Database, including DME or CRVO eyes initiating IDIs during 2015-2020. We classified all treated eyes as eligible or ineligible for pRCTs following major selection criteria of the MEAD and GENEVA trials, and evaluated three-, six-, and twelve-month changes in central retinal thickness (CRT) and visual acuity (VA) after initiating IDIs. RESULTS: We included 177 IDI-treated eyes (DME: 72.3%; CRVO: 27.7%), of which 39.8% and 55.1% were ineligible for DME and CRVO pRCTs, respectively. LogMAR-VA and CRT changes at different times were comparable in DME eyes eligible (LogMAR-VA difference: 0.11 to 0.16; CRT difference: -32.7 to -96.9 µm) and ineligible (LogMAR-VA difference: -0.01 to 0.15; CRT difference: -54.5 to -109.3 µm) for the MEAD trial. By contrast, CRVO eyes ineligible for the GENEVA trial had greater LogMAR-VA changes (0.37 ~ 0.50) than those eligible (0.05 ~ 0.13), with comparable CRT reductions (eligible eyes: -72.3 to -106.4 µm; ineligible eyes: -61.8 to -110.7 µm) (all p-values <0.05 of the mean differences between eligible and ineligible CRVO eyes for all follow-ups). CONCLUSIONS: IDIs had similar VA and CRT outcomes among DME eyes, regardless of pRCT-eligibility. However, among CRVO eyes, those ineligible for pRCTs showed greater deterioration in VA than those eligible.

PRESENTATIONS AND FACTORS AFFECTING OUTCOME OF RHEGMATOGENOUS RETINAL DETACHMENT WITH CHOROIDAL DETACHMENT: An Indo-Taiwanese Study.

PURPOSE: To report the clinical settings, management, and factors associated with outcomes of rhegmatogenous retinal detachment with concurrent choroidal detachment. METHODS: Retrospective, consecutive, multicenter case series from January 2014 to January 2021 were included. Cases were from a tertiary eye care center in India and Taiwan. RESULTS: Overall 303 eyes were included. Mean age was 43.72 ± 20.64 years (median 46). Best-corrected presenting visual acuity was 1.79 ± 0.92 logMAR (median 2.10) (Snellen 20/1,233). Forty-four patients (17.91%) received preoperative steroids. Final visual acuity was 1.33 ± 0.94 logMAR (median 1.10) (Snellen 20/427). Favorable anatomic outcome was seen in 200/303 (66%), whereas favorable functional outcome was seen in 128/303 (42.20%). Factors predicting favorable anatomic outcome were absence of phakic lens status (odds ratio [OR] 2.76), absence of proliferative vitreoretinopathy worse than Grade A (OR 7.69), use of preoperative steroids (OR 4.50), and use of an encircling band (3.85). Factors predicting favorable functional outcome were better presenting visual acuity (OR 3.03), absence of phakic lens status (OR 4.93), absence of proliferative vitreoretinopathy worse than Grade A (OR 10.41), and use of preoperative steroids (OR 7.24). CONCLUSION: Administration of preoperative steroids, use of an encircling band during surgery, and pseudophakic status of the eye were found to have better outcomes in rhegmatogenous retinal detachment with concurrent choroidal detachment.

Retinal vascular arcade angle as a biomarker for visual improvement after epiretinal membrane surgery.

OBJECTIVES: To investigate the changes in the temporal vascular angles after epiretinal membrane (ERM) surgery and utilize the angles to predict visual outcomes. METHODS: A total of 168 eyes from 84 patients with unilateral ERM who underwent vitrectomy were enrolled from a single institution. The angles of temporal venous (anglevein) and arterial arcades (angleartery) were measured on fundus photographs. The relationships between the angles and the best-corrected visual acuity (BCVA) were explored and multivariable logistic models and receiver operating characteristic (ROC) curves were analyzed to identify the factors that predicted visual outcomes. RESULTS: At baseline, both angleartery and anglevein were narrower in the eyes with ERM than the fellow eyes (p < 0.001 and 0.007) but had no correlation with the baseline BCVA (p = 0.754 and 0.804). Postoperatively, the angleartery and anglevein significantly widened (both p < 0.001) and a greater BCVA improvement was associated with a greater widening of the angleartery (p = 0.029) and anglevein (p = 0.050). Multivariable logistic analyses found a narrower baseline angleartery compared to the fellow eye had a higher chance for BCVA improvement ≧ 2 lines (Odds ratio = 0.97; 95% CI, 0.94-0.99; p = 0.016). ROC curve showed the baseline difference in the angleartery between bilateral eyes predicted BCVA improvement ≧ 2 lines (area under the curve = 0.74; p = 0.035), and a 0.73 sensitivity and 0.80 specificity with a cut-off value of -27.19 degrees. CONCLUSIONS: The retinal vascular angles widened after ERM surgery and the fundus photograph-derived angles may serve as a highly-accessible biomarker to predict postoperative visual outcomes.

Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial cells exposed to H2 O2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1ß, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A165 , with a dissociation constant of 2.2 × 10-14  M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.