Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea.

This study aims to compare the prevalence and seriousness of adverse events (AEs) among sedatives used in critically ill patients or patients undergoing invasive procedures and to identify factors associated with serious AEs. Retrospective cross-sectional analysis of sedative-related AEs voluntarily reported to the Korea Adverse Event Reporting System from 2008 to 2017 was performed. All AEs were grouped using preferred terms and System Organ Classes per the World Health Organization-Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious events. Among 95,188 AEs, including 3132 (3.3%) serious events, the most common etiologic sedative was fentanyl (58.8%), followed by pethidine (25.9%). Gastrointestinal disorders (54.2%) were the most frequent AEs. The most common serious AE was heart rate/rhythm disorders (33.1%). Serious AEs were significantly associated with male sex; pediatrics; etiologic sedative with etomidate at the highest risk, followed by dexmedetomidine, ketamine, and propofol; polypharmacy; combined sedative use; and concurrent use of corticosteroids, aspirin, neuromuscular blockers, and antihistamines (reporting odds ratio > 1, p < 0.001 for all). Sedative-induced AEs are most frequently reported with fentanyl, primarily manifesting as gastrointestinal disorders. Etomidate is associated with the highest risk of serious AEs, with the most common serious events being heart rate/rhythm disorders.

A Nationwide Survey on the Facilities and Personnel for Endoscopic Sedation: Results from 50 Qualified Endoscopy Units of Teaching Hospitals Accredited by the Korean Society of Gastrointestinal Endoscopy (KSGE).

BACKGROUND/AIMS: This study aimed to determine the current status of facilities, equipment, and personnel for endoscopic sedation from endoscopy units of representative hospitals in South Korea. METHODS: A questionnaire survey was conducted on 50 qualified endoscopy units accredited by the Korean Society of Gastrointestinal Endoscopy. RESULTS: All included endoscopy units had regulations and educational programs regarding sedation training for endoscopists and nursing personnel. There present one assisting nurse during endoscopy in 35 units (70%) and at least two nurses in 12 units (24.0%). All endoscopy units had examination rooms equipped with oxygen supply and suction systems. Endoscopist-directed sedation was performed in 48 units (96.0%). Propofol-based sedation was the most used sedation method. All units had a separate recovery bay. The daily number of patients per bed was greater than 10 in 17 units (34.0%). In 26 (52.0%) units, a single nurse cared for ≥10 patients per day. All the units fulfilled the discharge criteria. CONCLUSION: This study presents data regarding endoscopic sedation clinical practice in 50 endoscopy units in South Korea. This study presents the current status of endoscopic sedation clinical practice in 50 qualified endoscopy units accredited by the KSGE, which provide excellent quality management.

Simple transscleral fixation of IOL technique without tying up haptics.

AIM: To introduce a novel technique for transscleral fixation of the posterior chamber intraocular lens (PC-IOL) that requires no sutures on the IOL haptics. METHODS: Instead of suturing polypropylene onto the IOL haptics, the method simply winds the thread on the haptics. Fifteen eyes of 15 patients underwent this technique and were followed up for more than 18mo. Surgical outcomes and post-operative complications were evaluated and compared with those of the conventional transscleral fixation method. RESULTS: Postoperative cylinder was significantly lower in the thread winding group than in the conventional transscleral fixation method group (-1.02±0.46 diopters vs -1.57±0.77 diopters; P=0.01). Further, no postoperative complications, such as optic capture, IOL dislocation, and hyphema, were detected in the thread winding group. CONCLUSION: We believe that our thread winding technique is better than previously reported methods because it is simple, mechanically stable, and free from suture-related complications.

Sedentary Behavior and Sleep Duration Are Associated with Both Stress Symptoms and Suicidal Thoughts in Korean Adults.

Prolonged sedentary time and sleep deprivation are associated with mental health problems such as depression and stress symptoms. Moreover, mental illness is linked with suicidal thoughts and suicide attempts. However, it is not clear whether sedentary time and sleep duration are associated with stress symptoms and suicidal thoughts independent of physical activity. Thus, our study aimed to identify if sedentary time and sleep duration were associated with both stress symptoms and suicidal thoughts. The participants in present cross-sectional study were 4,674 general Korean adults (1,938 male; 2,736 female), aged ≥ 20 years. Prolonged sedentary time (≥ 420 min/day) was significantly associated with the increased risk of stress symptoms (OR, 1.30; 95% CI, 1.04-1.62) compared with sedentary time of < 240 min/day. The OR for stress symptoms was significant for individuals who had ≤ 5 h/day of sleep time (OR, 1.88; 95% CI, 1.48-2.38) compared with sleep duration of ≥ 7 h/day. Moreover, prolonged sedentary time (OR, 1.55; 95% CI, 1.01-2.42 in ≥ 420 min/day vs. < 240 min/day) and short sleep duration (OR, 1.75; 95% CI, 1.17-2.62 in ≤ 5 h/day vs. ≥ 7 h/day) were significantly associated with an increased risk for suicidal thoughts after adjusting for confounding factors including physical activity. Thus, prolonged sedentary time and sleep deprivation are independently associated with both the risk of stress symptoms and suicidal thoughts. From a public health perspective, reducing sedentary time and improvement of sleep deprivation may serve as an effective strategy for preventing mental illness.

Association between handgrip strength and cognitive impairment in elderly Koreans: a population-based cross-sectional study.

[Purpose] The purpose of this study was to investigate the association between handgrip strength and mild cognitive impairment in elderly adults. [Subjects] Study participants included 2,982 adults (1,366 males and 1,616 females), aged 65 years or older. [Methods] This population-based cross-sectional study used the baseline database from the Korean Longitudinal Study of Ageing. [Results] The odds ratio for mild cognitive impairment showed a significant linear decrease in relation to the quartile of handgrip strength, independent of potential covariates, in both men and women. Moreover, after excluding incident cases of mild cognitive impairment, the results showed that greater handgrip strength was associated with higher cognitive function scores in the elderly. [Conclusion] The findings presented here suggest that handgrip strength is associated with a risk of mild cognitive impairment in the Korean elderly. Moreover, greater handgrip strength is associated with higher cognitive function in cognitively normal elderly individuals.

Clinical effectiveness of topical cyclosporine a 0.05% after laser epithelial keratomileusis.

PURPOSE: To evaluate the effect of topical cyclosporine A 0.05% after laser epithelial keratomileusis (LASEK). METHODS: This retrospective nonrandomized comparative analysis was performed in 40 patients (80 eyes) with myopia who underwent flap-off LASEK. Twenty patients (group A) were treated with topical cyclosporine A 0.05% in combination with conventional treatment, and 20 patients (group B) received conventional treatment only. In each group, 10 patients had preoperative dry eye. Uncorrected visual acuity, refractive error, corneal haze grade, symptom score, and ocular surface parameters were measured in both groups before LASEK and at 1, 2, 4, and 8 weeks postoperatively. RESULTS: There were no significant differences between the groups in postoperative uncorrected visual acuity, spherical equivalent, corneal haze grade, Schirmer test values, and keratoepitheliopathy scores. Group A had lower symptom scores (0.80 ± 0.52 vs.1.35 ± 0.49; P < 0.01) and higher tear film break-up time (BUT) (8.05 ± 1.39 vs. 6.55 ± 1.39 seconds; P < 0.01) compared with group B at 4 weeks after LASEK. In addition, in preoperative dry eye patients, symptom scores and tear film BUT returned to preoperative level at 4 weeks postoperatively in group A, whereas they returned to preoperative level at 8 weeks in group B. CONCLUSIONS: Treatment with topical cyclosporine A 0.05% can improve ocular discomfort and increase tear film BUT during the early postoperative period, especially in patients with preoperative dry eye.

Effects of umbilical cord serum eye drops in a mouse model of ocular chemical burn.

PURPOSE: To evaluate the effect of umbilical cord serum (UCS) eye drops on corneal wound healing and haze in a mouse model of ocular chemical burn and compare with that of peripheral blood serum (PBS) eye drops or artificial tears (AT). METHODS: Chemical burn of the ocular surface was induced by 1N NaOH in C57BL/6 mice. Injured mice were topically treated with 20% UCS, 20% PBS, or AT four times daily. The changes of corneal epithelial defects and degree of haze were analyzed at 6 h, 1, 2, 3, 5, and 7 days, and histological examination was performed at 3 and 7 days. The concentration of IL-1ß in the cornea was measured by enzyme-linked immunosorbent assay at 7 days after treatment. RESULTS: The UCS group showed lower epithelial defect parameters compared with the PBS group at 1 and 2 days (p < 0.05), and with the AT group from 1-5 days (p < 0.05). The haze scores were significantly lower in the UCS group than in the PBS group at 2 and 3 days (p < 0.05), and in the AT group from 2-7 days (p < 0.05). Histological examination showed better epithelial integrity and lower stromal inflammation and edema in the UCS group than the other groups. IL-1ß levels were 99.71 ± 85.22 and 230.76 ± 102.67 pg/ml in the UCS and PBS groups, respectively (p = 0.03). CONCLUSIONS: UCS eye drops are more effective in improving corneal wound healing and reducing corneal haze compared with PBS eye drops and AT in experimental chemical burns.

Design and synthesis of 4-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF1 production.

A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production.

Structure-activity relationship of indoline-2-carboxylic acid N-(substituted)phenylamide derivatives.

Chroman derivatives exhibited potent inhibitory activity of NF-kappaB. For SAR, the chroman scaffold was modified with an indoline moiety. A series of indoline-2-carboxylic acid N-(substituted)phenylamide derivatives were synthesized to explore their inhibitory activities of NF-kappaB and they were also evaluated for cytotoxicity against various cancer cell lines. Since intermediates with Boc showed outstanding results, various substituents in place of the Boc group were introduced additionally and these compounds were also evaluated for SAR.

Suppressor of cytokine signaling 3 suppresses hepatitis C virus replication in an mTOR-dependent manner.

We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection.