Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment.

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was "Uncertain efficacy". In terms of motivations, the willing group ranked "Better therapeutic benefits" (35.0%), "Professional monitoring" (34.3%), and "Trust in healthcare professionals" (33.1%) as their top three reasons, whereas the unwilling participants indicated "Full comprehension of the protocol" (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

Diagnostic performance of wide-field optical coherence tomography angiography in detecting open-angle glaucoma in high myopia.

PURPOSE: To compare the diagnostic performance of the capillary density (CD) of the central 1-6 mm and peripheral 6-12 mm annular regions in detecting open-angle glaucoma in high myopia (HM) using 15 × 12 mm wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). METHODS: The study enrolled 206 and 103 eyes with HM and highly myopic open-angle glaucoma (HM-OAG), respectively. WF SS-OCTA images centred on the fovea were obtained to analyse the changes in the CD in the 1-3 mm, 3-6 mm, 6-9 mm, and 9-12 mm annular regions. CD of the superficial capillary plexus (SCP) was measured with the built-in software. The area under the receiver operating characteristic curve (AUROC) of each region was compared. RESULTS: The diagnostic performance of the SCP CD in the central 1-6 mm annular region (AUROC = 0.849) was better than that in the peripheral 6-12 mm annular region (AUROC = 0.756, p = 0.001). The annular AUROCs of SCP CD peaked in the 3-6 mm annular region (AUROC = 0.858) and gradually decreased with increasing diameter and were lower than the corresponding AUROCs of the ganglion cell-inner plexiform layer thickness (p < 0.05 for all comparisons). SCP CD of the inferior quadrant in the 3-6 mm annular region had the best diagnostic performance (AUROC = 0.859). CONCLUSION: The SCP CD in the central 1-6 mm annular region exhibited better diagnostic performance for the detection of HM-OAG in HM. The assessment of more peripheral regions has no added value in detecting glaucoma in HM.

Macular and submacular choroidal microvasculature in patients with primary open-angle glaucoma and high myopia.

AIMS: To characterise the influence of primary open-angle glaucoma (POAG) and high myopia (HM) on the macular and choroidal capillary density (CD). METHODS: Two hundred and seven eyes were enrolled, including 80 POAG without HM, 50 POAG with HM, 31 HM without POAG and 46 normal controls. A fovea-centred 6×6 mm optical coherence tomography angiography scan was performed to obtain the CD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris. Macular and choroidal CDs were compared among the groups and the association of CDs with visual field mean deviation (MD) was determined using linear regression models. RESULTS: Compared with normal eyes, SCP CD was decreased in the POAG without HM group (p<0.05), while DCP CD was significantly decreased in the HM without POAG group (p<0.05). Both SCP and DCP CDs were significantly decreased in the POAG with HM group (p<0.05). CD reduction occurred mainly in the outer rather than inner ring of the 6×6 mm scan size. In multivariate regression analysis, worse MD was associated with lower CD in the outer ring of the SCP in all the HM eyes (p<0.05). CONCLUSIONS: POAG and HM reduced macular CD in different layers of the retinal capillary plexus and both particularly in the outer ring of the 6×6 mm scans. Furthermore, assessment of the CD in the outer ring of the SCP may facilitate the diagnosis of glaucoma in eyes with HM.

Efficacy and safety of trabeculectomy versus peripheral iridectomy plus goniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre, non-inferiority, randomised controlled trial (the TVG study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a major subtype of glaucoma that accounts for most bilateral glaucoma-related blindness globally. Filtering surgery is a conventional strategy for PACG, yet it has a long learning curve and undesirable disastrous complications. Minimally invasive glaucoma surgery (MIGS) plays an increasing role in the management of glaucoma due to its safer and faster recovery profile; cataract surgery-based MIGS is the most commonly performed such procedure in PACG. However, for patients with a transparent lens or no indications for cataract extraction, incorporation of MIGS into PACG treatment has not yet been reported. Therefore, this multicentre, non-inferiority, randomised controlled clinical trial aims to compare the efficacy and safety of trabeculectomy versus peripheral iridectomy plus an ab interno goniotomy in advanced PACG with no or mild cataracts. METHODS AND ANALYSIS: This non-inferiority, multicentre, randomised controlled trial will be conducted at seven ophthalmic departments and institutes across China. Eighty-eight patients with no or mild cataracts and advanced PACG will be enrolled and randomised to undergo trabeculectomy or peripheral iridectomy plus ab interno goniotomy. Enrolled patients will undergo comprehensive ophthalmic examinations before and after surgery. The primary outcome is intraocular pressure (IOP) at 12 months postoperatively. The secondary outcomes are cumulative success rate of surgery, surgery-related complications and number of IOP-lowering medications. Participants will be followed up for 36 months postoperatively. ETHICS AND DISSEMINATION: The study protocol was approved by the ethical committees of the Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ191) and of all subcentres. All participants will be required to provide written informed consent. The results will be published in peer-reviewed journals and disseminated in international academic meetings. TRIAL REGISTRATION NUMBER: NCT05163951.

Clinical and Gene Features of SARS-CoV-2-Positive Recurrence in Patients Recovered From COVID-19.

There are still frequent reports that a number of recovered coronavirus disease 2019 (COVID-19) patients following discharge have re-detectable positive (RP) results by RT-PCR. Understanding the clinical and molecular characteristics of RP patients may have implications for curbing the COVID-19 pandemic. In this study, 318 COVID-19 convalescent patients, including 59 RP patients and 259 non-RP (NRP) patients, were enrolled. Among RP patients, women accounted for a significantly high proportion (67.8%), and the titers of IgG and IgM antibodies in this group were also significantly high. Differentially expressed genes (DEGs), including 692 upregulated and 383 downregulated genes, overlapped in two public GEO datasets containing RP and NRP blood cell samples. Enrichment analysis indicated that these DEGs were related to several key signaling pathways, such as viral infection, immune activation, and inflammatory responses. Importantly, 59 indicator genes constituting the core network exhibited high diagnostic values and were correlated with markers of different immune cells. Among these, 12 drug-related genes were associated with the RP results. Our work suggests that, in addition to clinically available features, blood cell transcriptome sequencing can be performed to obtain gene signatures for diagnosis of RP patients.

Ocular Factors of Fractal Dimension and Blood Vessel Tortuosity Derived From OCTA in a Healthy Chinese Population.

Purpose: To identify the ocular factors of microvascular fractal dimension (FD) and blood vessel tortuosity (BVT) of macula measured with optical coherence tomography angiography (OCTA) in a healthy Chinese population. Methods: Healthy subjects without ocular disorders were recruited at Zhongshan Ophthalmic Center. The FD and BVT in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at the macula were obtained from OCTA images. The FD was calculated using the box-counting method, and the BVT was defined as the ratio of the actual distance between two points to the straight distance on the skeletonized image. Univariate and stepwise multivariate linear regression analyses were performed to identify the ocular factors of FD and BVT, and the results are presented as coefficients and 95% confidence intervals (CIs). Only the right eye of each subject was included. Results: A total of 2189 healthy individuals (2189 eyes) were included with a mean age of 49.9 ± 13.2 years; 54.4% were female. In the multivariate model, the FD in the SCP was significantly associated with higher intraocular pressure (IOP) (ß = 0.204; 95% CI, 0.073-0.335; P < 0.001), axial length (AL) (ß = -0.875; 95% CI, -1.197 to -0.552; P < 0.001; R2 = 0.26; root mean square error [RMSE] = 7.78). The FD in the DCP was significantly associated with best-corrected visual acuity (ß = -6.170; 95% CI, -10.175 to -2.166; P = 0.003) and anterior chamber depth (ß = -0.348; 95% CI, -0.673 to -0.023; P = 0.036; R2 = 0.10; RMSE = 2.58). Superficial BVT was independently associated with IOP (ß = -0.044; 95% CI, -0.079 to -0.009; P = 0.012) and AL (ß = 0.097; 95% CI, 0.014-0.181; P = 0.022; R2 = 0.15; RMSE = 2.02). Deep BVT was independently associated with IOP (ß = -0.004; 95% CI, -0.009 to -0.0005; P = 0.028) and lens thickness (ß = 0.036, 95% CI, 0.003-0.060; P = 0.028; R2 = 0.07, RMSE = 0.25). Conclusions: The IOP and AL were dependent ocular parameters variables of FD and BVT in the SCP in this healthy population. The FD in the DCP was also influenced by visual acuity and anterior chamber depth. These factors should be considered when microvascular geometrics are used in the future studies. Translational Relevance: This work discovered the influence factors of OCTA geometrics parameters for further establishment of diagnostic model or method for glaucoma and other microvasculature-related ocular diseases.

Comparison of Non-contact Tonometry and Goldmann Applanation Tonometry Measurements in Non-pathologic High Myopia.

Purpose: To compare intraocular pressure (IOP) values obtained using Goldmann applanation tonometry (IOPGAT) and non-contact tonometry (IOPNCT) in a non-pathologic high myopia population. Methods: A total of 720 eyes from 720 Chinese adults with non-pathologic high myopia were enrolled in this cross-sectional study. Demographic and ocular characteristics, including axial length, refractive error, central corneal thickness (CCT), and corneal curvature (CC) were recorded. Each patient was successively treated with IOPNCT and IOPGAT. Univariate and multivariable linear regression analyses were conducted to detect factors associated with IOPNCT and IOPGAT, as well as the measurement difference between the two devices (IOPNCT-GAT). Results: In this non-pathologic high myopia population, the mean IOPNCT and IOPGAT values were 17.60 ± 2.76 mmHg and 13.85 ± 2.43 mmHg, respectively. The IOP measurements of the two devices were significantly correlated (r = 0.681, P < 0.001), however, IOPNCT overestimated IOPGAT with a mean difference of 3.75 mmHg (95% confidence interval: 3.60-3.91 mmHg). In multivariate regression, IOPNCT was significantly associated with body mass index (standardized ß = 0.075, p = 0.033), systolic blood pressure (SBP) (standardized ß = 0.170, p < 0.001), and CCT (standardized ß = 0.526, p < 0.001). As for IOPGAT, only SBP (standardized ß = 0.162, p < 0.001), CCT (standardized ß = 0.259, p < 0.001), and CC (standardized ß = 0.156, p < 0.001) were significantly correlated. The mean IOPNCT-GAT difference increased with younger age (standardized ß = -0.134, p < 0.001), higher body mass index (standardized ß = 0.091, p = 0.009), higher SBP (standardized ß = 0.074, p = 0.027), thicker CCT (standardized ß = 0.506, p < 0.001), and lower IOPGAT (standardized ß = -0.409, p < 0.001). Conclusion: In the non-pathologic high myopia population, IOPNCT overestimated IOPGAT at 3.75 ± 2.10 mmHg. This study suggests that the difference between the values obtained by the two devices, and their respective influencing factors, should be considered in the clinical evaluation and management of highly myopic populations.

Verdinexor, a Selective Inhibitor of Nuclear Exportin 1, Inhibits the Proliferation and Migration of Esophageal Cancer via XPO1/c-Myc/FOSL1 Axis.

Esophageal carcinoma (EC) ranks sixth among cancers in mortality worldwide and effective drugs to reduce EC incidence and mortality are lacking. To explore potential anti-esophageal cancer drugs, we conducted drug screening and discovered that verdinexor, a selective inhibitor of nuclear exportin 1 (XPO1/CRM1), has anti-esophageal cancer effects both in vivo and in vitro. However, the mechanism and role of verdinexor in esophageal cancer remain unknown. In the present study, we observed that verdinexor inhibited the proliferation and migration of EC cells in vitro and suppressed tumor growth in vivo. Additionally, we found that verdinexor induced cleavage of PARP and downregulated XPO1, c-Myc, and FOSL1 expression. RNA-sequence analysis and protein-protein interaction (PPI) analysis revealed that verdinexor regulated the XPO1/c-Myc/FOSL1 axis. The results of immunoprecipitation and proximity ligation assays confirmed that verdinexor disrupted the interaction between XPO1 and c-Myc. Overexpression of c-Myc rescued the inhibition of cell proliferation and cell migration caused by verdinexor. Overexpressed FOSL1 restored the inhibited migration by verdinexor. Taken together, verdinexor inhibited cell proliferation and migration of esophageal cancer via XPO1/c-Myc/FOSL1 axis. Our findings provide a new option for the development of anti-esophageal cancer drugs.

[Heat-sensitive moxibustion of different suspension moxibustion methods and imitation moxibustion apparatus on moxibustion sensation and clinical efficacy in knee osteoarthritis].

OBJECTIVE: To observe the moxibustion sensation and the clinical therapeutic effect of heat-sensitive moxibustion of two different suspension moxibustion methods and imitation moxibustion apparatus on mild to moderate knee osteoarthritis (KOA), and compare the therapeutic effect of different moxibustion methods. METHODS: A total of 90 patients with mild to moderate KOA were randomized into a hand-held group (30 cases, 1 case dropped off), an imitation moxibustion apparatus group (30 cases) and a moxibustion shelf group (30 cases, 1 case dropped off). Ashi point, Dubi (ST 35), Neixiyan (EX-LE 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Liangqiu (ST 34) and Xuehai (SP 10) were selected as the frequent acupoint areas to explore and determine the heat-sensitive acupoints, after that, hand-held suspension moxibustion, suspension moxibustion with imitation moxibustion apparatus and suspension moxibustion with moxibustion shelf were adopted in the 3 groups respectively. The treatment was given once every 2 days, and totally 10-time treatment was required in the 3 groups. The moxibustion sensation (composition of moxibustion sensation, number of moxibustion sensation types in individuals and moxibustion sensation intensity) after each treatment, the visual analogue scale (VAS) score, the Lysholms knee function score and the depth of effusion and thickness of synovial hyperplasia of affected knee joint before and after treatment were observed, and the clinical therapeutic efficacy was compared in the 3 groups. RESULTS: The compositions of moxibustion sensation and numbers of moxibustion sensation types in individuals in the hand-held group and the moxibustion shelf group were richer, the moxibustion sensation intensity was higher than that in the imitation moxibustion apparatus group (P<0.01, P<0.05). After treatment, the VAS scores were decreased, the Lysholms knee function scores were increased compared before treatment in the 3 groups (P<0.01); the VAS score in the hand-held group was lower than the imitation moxibustion apparatus group (P<0.05), the Lysholms knee function scores in the hand-held group and the moxibustion shelf group were higher than the imitation moxibustion apparatus group (P<0.05). After treatment, the depth of effusion and thickness of synovial hyperplasia of affected knee joint were decreased compared before treatment in the 3 groups (P<0.01), and those in the hand-held group and the moxibustion shelf group were lower than the imitation moxibustion apparatus group (P<0.05). The cured and markedly effective rate in the hand-held group was 79.3% (23/29), which was better than 36.7% (11/30) in the imitation moxibuation apparatus group and 58.6% (17/29) in the moxibustion shelf group (P<0.01, P<0.05). CONCLUSION: Heat-sensitive moxibustion can effectively treat knee osteoarthritis, while the different suspension moxibustion methods have an influence on clinical therapeutic effect, hand-held suspension moxibustion has the best efficacy.

Longitudinal Changes in Macular Optical Coherence Tomography Angiography Metrics in Primary Open-Angle Glaucoma With High Myopia: A Prospective Study.

Purpose: To characterize longitudinal changes in macular microvasculature as quantified from optical coherence tomography angiography (OCTA) metrics in primary open-angle glaucoma (POAG) eyes with and without high myopia. Methods: In total, 63 and 61 POAG eyes with and without high myopia, respectively, underwent swept-source OCTA imaging in at least four follow-up visits at an ophthalmic center, with a scanning protocol of 3- × 3-mm centered at the fovea. The foveal avascular zone (FAZ) area, FAZ circularity, and vessel density (VD) in both the superficial (SCP) and deep capillary plexuses (DCP) were measured. The rate of change in macular OCTA metrics over time was estimated using linear mixed-effects models in both groups of POAG eyes. Results: The mean follow-up time and number of visits were 27.72 ± 8.57 months and 8.5 (8 to 13) times, and 30.95 ± 10.19 months and 10 (8‒13) times in POAG eyes with and without high myopia, respectively. VD in the DCP reduced significantly more quickly in POAG eyes with high myopia than in those without high myopia (-5.14%/year vs. -3.71%/year, P = 0.008). Moreover, lower baseline VD in the DCP was significantly associated with faster VD reduction in POAG with high myopia eyes (P < 0.001). Conversely, the VD reduction rate in the SCP, FAZ area, and FAZ circularity in both the SCP and DCP were similar in both groups (all Ps > 0.05). Conclusions: VD in DCP reduced significantly more quickly in POAG eyes with high myopia over time. Density in the DCP reduced more quickly when baseline VD was low.

Performance of Topological Perception in the Myopic Population.

Purpose: Discriminating objects' topological property (TP) is a primitive function of visual representation, which is reported to be associated with magnocellular (M) visual pathway, temporal lobe (TL), and superior colliculus (SC)-pulvinar subcortical pathway. Previous studies have shown that M pathway and TL were affected in high myopia (HM) subjects. The study was accordingly designed to explore whether topological perception performance was abnormal in HM subjects. Methods: 30 mildly myopic, 25 moderately myopic, 35 highly myopic, and 20 emmetropic subjects were enrolled. All participants underwent a comprehensive ophthalmological assessment including automated refraction, intraocular pressure, Humphrey 10-2 standard automated perimetry, ocular fundus photography and swept-source optical coherence tomography. Defined by differences in hole, TP and non-TP discrimination with letters "E", "S", "P", "d" as stimuli in the central and peripheral regions was performed using the MATLAB 2017 software. d-primes extracted from the software were analyzed within each group. The correlation of peripheral TP/non-TP deficit with spherical equivalent (SE), axial length (AL) and average peripapillary retinal nerve fiber layer (RNFL) thickness was performed. Results: The patterns of topological perception performance were similar among the groups. TP discrimination peripherally was significantly better than that centrally in the mild myopia (P < .001), moderate myopia (P < .001), high myopia (P < .001) and emmetropia groups (P = .001). In the peripheral region, TP d-prime scores were significantly better than non-TP d-prime scores (all P < .001). The main and interaction effects of eccentricity and stimulus type were statistically significant(P < .05). There was no statistically significant correlation between peripheral TP/non-TP deficit and SE, AL or average RNFL thickness (P > .05). Conclusions: The current study first showed that patterns of topological perception among the myopic population were similar and not affected by the severity of myopia.