Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Failed Thrombus Aspiration and Reduced Myocardial Perfusion in Patients With STEMI and Large Thrombus Burden.

BACKGROUND: Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization. OBJECTIVES: The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB. METHODS: In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI (Thrombolysis In Myocardial Infarction) flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group. RESULTS: The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure. CONCLUSIONS: TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non-left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127).

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

Outcomes of retropupillary iris claw lens implantation in patients with intraocular lens dislocation and low (less than 1000 cells/mm2) corneal endothelial cell density.

BACKGROUND: Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm2) ECD. METHODS: We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm2 and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery. RESULTS: Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57-76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07-89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01). CONCLUSIONS: R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Pachychoroid Spectrum Disease: Comparison of Patients with Central Serous Chorioretinopathy Complicated with Pachychoroid Neovasculopathy.

PURPOSE: This study aimed to determine the incidence and visual outcomes of pachychoroid neovasculopathy (PNV) in patients initially diagnosed with central serous chorioretinopathy (CSC). METHODS: In this study, 144 patients aged 20 to 55 years with treatment-naive chronic CSC, defined as the persistence of subretinal fluid (SRF) for ≥6 months, were retrospectively enrolled. Patients with PNV at the initial evaluation were categorized as group 1, whereas those who developed new-onset PNV during follow-up were categorized as group 2. Patients without PNV until the end of the follow-up were categorized as group 3. RESULTS: Over a mean follow-up period of 49.9 ± 39.9 months, new-onset PNV was diagnosed in 11.8% of patients with CSC. The time taken to reach the initial resolution was longest in group 1 (group 1, 11.13 ± 10.70 months; group 2, 8.14 ± 7.90 months; group 3, 7.32 ± 9.55 months), although these differences were not statistically significant. The numbers of injections needed to achieve initial resolution were 3.76 ± 5.90, 1.64 ± 2.06, and 1.74 ± 4.33 in groups 1, 2, and 3, respectively, with no significant differences. SRF recurrence was recorded in seven patients (29.2%) in group 1, nine (64.3%) in group 2, and 28 (26.7%) in group 3. The recurrence rates were significantly higher in group 2 than those in group 1 or 3. At the end of the follow-up period, significant improvements in best-corrected visual acuity were achieved in groups 1 and 3, compared with baseline, but not in group 2. CONCLUSIONS: Patients with chronic CSC with new-onset PNV exhibited higher SRF recurrence and worse visual outcomes compared to those with initial PNV or those with chronic CSC without PNV. Our study emphasizes the importance of routine screening for prompt diagnoses of new-onset PNV in individuals with chronic CSC.

Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Exploring the Challenges of Distinguishing Punctate Inner Choroidopathy from Multifocal Choroiditis and Panuveitis.

PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.

Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals.

Despite of the substantial potential of human-derived retinal organoids, the degeneration of retinal ganglion cells (RGCs) during maturation limits their utility in assessing the functionality of later-born retinal cell subtypes. Additionally, conventional analyses primarily rely on fluorescent emissions, which limits the detection of actual cell functionality while risking damage to the 3D cytoarchitecture of organoids. Here, an electrophysiological analysis is presented to monitor RGC development in early to mid-stage retinal organoids, and compare distinct features with fully-mature mouse retina. This approach utilizes high-resolution 3D printing of liquid-metal microelectrodes, enabling precise targeting of specific inner retinal layers within organoids. The adaptable distribution and softness of these microelectrodes facilitate the spatiotemporal recording of inner retinal signals. This study not only demonstrates the functional properties of RGCs in retinal organoid development but also provides insights into their synaptic connectivity, reminiscent of fetal native retinas. Further comparison with fully-mature mouse retina in vivo verifies the organoid features, highlighting the potential of early-stage retinal organoids in biomedical research.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Factors predicting redislocation or suture break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation after secondary scleral-fixated IOL (SF IOL) surgery. SETTING: 2 tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SF IOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SF IOL surgery between June 2014 and December 2019 at 2 tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: 237 eyes of 225 patients (169 [75.1%] men) were included. The redislocation group was more likely to have a younger mean age at the initial SF IOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P = .008), have a prior history of a previous suture break (23 eyes, 52.3% vs 1 eye, 0.5%; P < .001), and have undergone the initial SF IOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P = .002) than was the no-redislocation group. In addition, the redislocation group had a higher occurrence of complications ( P < .001). Multivariate regression revealed that younger age, left eye involvement, aphakic status before the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P < .05) associated with redislocation. CONCLUSIONS: Younger age, left eye involvement, postoperative complications such as ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

PURPOSE: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. METHODS: A total of 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (cytomegalovirus, varicella zoster virus, and herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1, 2006, to June 30, 2023, in a single medical center were retrospectively enrolled. RESULTS: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, nine eyes (24.3%) with viral retinitis and five eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and six eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the 1st postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence, 0.21 vs. 0.85; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval, 1.22-17.27; p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. CONCLUSIONS: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.

Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.

Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of PRDM13 causing North Carolina macular dystrophy in Korea.

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families. Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools. Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13. Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Distal Radial Access for Coronary Procedures in a Large Prospective Multicenter Registry: The KODRA Trial.

BACKGROUND: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation. OBJECTIVES: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice. METHODS: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure. RESULTS: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure. CONCLUSIONS: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700).

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration.

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 µm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium-indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm-2) to elicit neural responses in the retina. Their low Young's modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.