Abstract Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.
To facilitate the prompt diagnosis of recurrence and treatment of uveal melanoma (UVM), the potential diagnostic markers of UVM need to be identified. The Cancer Genome Atlas (TCGA) database offers not only RNA sequence data on UVM but also the clinical characteristics of patients. The weighted gene co-expression network analysis (WGCNA) was conducted for the construction of the co-expression modules, based on how modules correlate with clinic characteristics were explored. The co-expression modules comprised of 6023 mRNA, 632 miRNA and 3042 LncRNA in 80 samples were identified, which closely associated with several clinical characteristics. A negative correlation with blue and brown modules in mRNA was revealed by overall survival (OS) time, disease free survival (DSS) time and progression free interval (PFI) time, while yellow, green and grey modules demonstrated a positive correlation. Modules turquoise in miRNA and module blue in LncRNA were most involved in survival time. The hub gene in mRNA-miRNA-LncRNA, PLCD1, LZTFL1, LCP2, GEM, NUSAP1, miR-937 and ENSG00000249846, is essential for the development of UVM. By providing a framework of co-expression gene modules for UVM, this paper found out about several diagnostic markers that could assist in the identification of recurring UVM and the treatment of it.
Background/aim To evaluate the clinical outcomes of penetrating canaloplasty in traumatic angle recession glaucoma at 1 year. Methods Patients with angle recession glaucoma underwent penetrating canaloplasty, a new Schlemm’s canal-based internal drainage procedure, which creates a direct canal for flow of aqueous humour from the anterior chamber to the ostia of Schlemm’s canal via a window created at the corneal scleral bed without use of antimetabolites. Postoperative intraocular pressure (IOP), number of glaucoma medications, and procedure-related complications were evaluated. Success was defined as an IOP ≤21 mm Hg without (complete) or with (qualified) use of glaucoma medication. Results Forty eyes in 40 patients with angle recession glaucoma underwent successful circumferential catheterisation. The mean patient age was 42±13 years. In patients with penetrating canaloplasty that was deemed to be completely successful, the mean IOP decreased from a preoperative value of 37.8±12.3 mm Hg on 3.3±1.2 anti-glaucoma medications to 18.5±6.4 mm Hg on 1.2±1.4 medications, 14.9±4.6 mm Hg on 0.1±0.5 medications, 15.7±5.4 mm Hg on 0.1±0.4 medications and 14.8±3.6 mm Hg on 0.1±0.5 medications at 1, 3, 6 and 12 months postoperatively (p<0.05). Complete success was achieved in 35/40 eyes (87.5%) at 6 months and in 34/38 (89.5%) at 12 months. Hyphema (18/40, 45.0%) and transient IOP elevation (≥30 mm Hg, 9/40, 22.5%) were the most common postoperative complications. Conclusion Penetrating canaloplasty significantly reduces IOP and has a high success rate in angle recession glaucoma. Trial registration number ChiCTR1900020511.
Background/aims Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). Methods This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. Results This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (β VD =−0.39, β VSD =−10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. Conclusion Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.
Précis: Penetrating canaloplasty was safe and effective for the management of refractory childhood glaucoma. Purpose: The purpose of this paper is to report the safety and efficacy of penetrating canaloplasty for the management of childhood glaucoma. Materials and Methods: This single-center prospective interventional case series enrolled 50 eyes of 32 patients with childhood glaucoma between July 2017 and July 2020. Penetrating canaloplasty to create direct communication between the anterior chamber and tensioning suture-dilated the Schlemm canal was performed through a trabecular meshwork ostium in the affected eyes. Preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, and procedure-related complications were recorded. Qualified and complete success was defined as IOP≥5 and ≤21 mm Hg with or without glaucoma medications, respectively. Results: A total of 43 eyes (86.0%) achieved 360 degrees catheterization of Schlemm canal and completed penetrating canaloplasty. The median age at surgery was 5 years (range, 10 d–17 y, mean 6.20±5.46 y). The mean IOP decreased from 33.11±10.89 mm Hg on 2 medications (median, range: 0–5) before surgery to 13.46±4.71 mm Hg on 0 medications (median, range:0–2) postoperatively at 12 months ( P <0.001). Complete and qualified success rates were 81.08% and 89.19%, respectively, at the 12-month follow-up. Hyphema (6/43, 13.95%) and a transient shallow anterior chamber with hypotony (5/43, 11.63%) were the most commonly observed early complications. Conclusion: Penetrating canaloplasty demonstrated good safety and efficacy in eyes with childhood glaucoma, and may be considered an option for managing refractory childhood glaucoma.
Herein, the authors describe an initial case report of widefield swept-source optical coherence tomography angiography (SS-OCTA) in Vogt-Koyanagi-Harada (VKH) disease. When compared to fluorescent angiography, indocyanine green angiography, and enhanced-depth OCT - upon which the revised criteria for VHK are based - widefield SS-OCTA enables detection of vitreous inflammation, noninvasive identification of characteristic areas of flow void at the level of choriocapillaris in the acute phase and may be a novel valuable tool not only for noninvasive diagnosis and monitoring of disease progression, persistence, resolution, and recurrence to guide therapy in VKH disease in the future. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:407-412.].
To report the efficacy of a bleb-independent penetrating canaloplasty in the management of glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE).Prospective, non-comparative clinical study.Penetrating canaloplasty was performed on 35 eyes from 35 patients with GS-ICE and medically uncontrolled intraocular pressure (IOP) between January 2018 and April 2020. Patients were followed up at 1 week, months 1, 3, 6, 12 postoperatively, and semi-annually thereafter. The IOP, anti-glaucoma medication, and surgery-related complications were recorded. Surgical success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg without (complete success) or with/without (qualified success) IOP-lowering medication.A total of 29 eyes (82.9%) had 360° catheterization and successfully received penetrating canaloplasty. Of these eyes, 24 (82.8%) achieved qualified success and 22 (75.9%) achieved qualified success at 12 months after surgery. The mean IOP decreased from 39.5 ± 11.8 mmHg on 2.9 ± 1.0 medications before surgery to 16.6 ± 5.3 mmHg (P < .001) on 0.2 ± 0.6 medications (P < .001) at 12 months postoperatively, respectively. Hyphema (37.9%), transient hypotony (34.5%), and transient postoperative IOP elevation (≥ 30 mmHg, 17.9%) were the most commonly observed early complications at the 1 week and 1 month visits. From 1 month and beyond, all treated eyes showed no obvious bleb at the operation quadrant.Penetrating canaloplasty rescued the inner aqueous outflow in ICE eyes and demonstrated acceptable success in IOP control with few complications, providing a new option for the management of GS-ICE.
To test the hypothesis that human eyes have a central tendency to be free of higher-order aberrations by analyzing wavefront aberrations for two young populations of respectively emmetropic and myopic subjects. Both right and left eyes of 75 emmetropes and 196 myopes were measured for corneal wavefront aberration using a Humphrey corneal topographer and for the whole eye wavefront aberration using a WASCA wavefront sensor without pupil dilation. 35 Zernike aberration coefficients over a 6.0 mm pupil diameter were derived, and statistics of the higher-order terms (3rd to 5th orders) were tested. When signed Zernike aberrations of the right and left eyes were averaged together for the emmetropes, three higher-order modes (j=6, 12 and 13) were significantly different from zero in both the cornea and the whole eye (P<0.0005), and three additional terms (j=14, 15 and 17) were statistically non-zero for the whole eye. As the signs of y-axis asymmetrical terms in the left eye were flipped, three more terms in either the cornea (j=8, 18 and 19) or the whole eye (j=8, 10 and 20) became statistically non-zero. For the myopes, 8 corneal terms and 5 whole-eye terms were statistically non-zero when the two eyes were averaged together. As the signs flipped, the majority of the Zernike aberration terms were statistically different from zero. Human eyes have systematical higher order aberrations in population, and factors that cause bilateral symmetry of wavefront aberrations between the right and left eyes made important contribution to the systematical aberrations. Poner a prueba la hipótesis de que el ojo humano, en promedio, tiende a estar libre de aberraciones de alto orden. Para ello se analizó la aberración de onda en dos poblaciones distintas: una compuesta por jóvenes emétropes, la otra por jóvenes miopes. Se estudiaron los ojos izquierdo y derecho de 75 emétropes y de 196 miopes. En cada ojo, sin dilatar la pupila, se midieron las aberraciones corneales utilizando un topógrafo corneal Humprey y también se obtuvo la aberración de onda de toda la óptica ocular por medio de un sensor de frente de onda WASCA. A partir de estos datos se calcularon los 35 coeficientes de aberración de Zernike que caracterizan cada patrón de aberración para un diámetro de pupila de 6,00 mm, realizándose a continuación un análisis estadístico de los términos de alto orden (del 3° al 5° orden). Cuando para los emétropes se promedian los coeficientes de aberración de Zernike para los ojos izquierdo y derecho, manteniendo su signo, hay tres modos de alto orden (j=6, 12 y 13) que resultan ser significativamente distintos de cero, tanto para la córnea como para todo el ojo. Además, otros tres términos (j=14, 15 y 17) resultaron ser también estadísticamente distintos de cero cuando se analiza todo el ojo en su conjunto. Cuando se cambia para el ojo izquierdo el signo de los coeficientes correspondientes a los términos de aberración que son asimétricos respecto al eje y, hay tres términos más (en la córnea: j=8, 18 y 19, y para todo el ojo: j=8, 10 y 20) que pasan a ser estadísticamente distintos de cero. En lo que respecta a los miopes, hay 8 términos para la córnea y 5 términos para todo el ojo que resultan ser estadísticamente distintos de cero cuando se promedian los dos ojos de todos los integrantes del grupo. Cuando se cambian los signos, de forma análoga al grupo anterior, la mayoría de los coeficientes de aberración de Zernike resultan ser estadísticamente distintos de cero. El ojo humano presenta de forma sistemática aberraciones de alto orden. Los factores que provocan la simetría bilateral de la aberración de onda entre el ojo izquierdo y derecho de cada individuo contribuyen de manera importante a la presencia de dichas aberraciones sistemáticas.
Abstract Background Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy. Methods AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time. Discussion This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies. Trial registration ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255.
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