1.Correlation analysis of signal characteristics of subretinal hyperreflective material and neovascular morphology in neovascular age-related macular degeneration
Jiaxin PU ; Yuying JI ; Xuenan ZHUANG ; Xinlei HAO ; Feng WEN
Chinese Journal of Ocular Fundus Diseases 2025;41(8):605-612
Objective:To observe the signal intensity and homogeneity of subretinal hyperreflective material (SHRM) in neovascular age-related macular degeneration (nAMD) and preliminarily analyze its relationship with macular neovascularization (MNV) morphology.Methods:A prospective cross-sectional observational study. Forty-six eyes of 46 nAMD patients with SHRM who initially visited Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 2022 to March 31, 2023 were enrolled. Optical coherence tomography (OCT) examination was performed according to a standardized protocol, and 3D Slicer software was used for three-dimensional reconstruction of SHRM lesions. Signal intensity was represented by the mean gray value (mGV) of the three-dimensional lesion area, and homogeneity was represented by the standard deviation of gray values (GV-SD). OCT angiography (OCTA) was used to scan the 6 mm×6 mm area of the macula. FIJI and Angio Tool software were used to measure MNV vascular network total area, perimeter, maximum and minimum diameters, maximum vessel diameter, vascular component area, total number of vascular network junctions and endpoints, vessel dispersion, and mean lacunarity. The ratio of maximum to minimum diameter of the vascular network, average vessel length, vessel density, and vessel fractal index were calculated. Using the mean mGV of the total sample as the standard, the eyes were divided into low-density SHRM group (20 eyes) and high-density SHRM group (26 eyes); using the mean GV-SD of the total sample as the standard, the eyes were divided into homogeneous SHRM group (29 eyes) and non-homogeneous SHRM group (17 eyes). The morphological characteristics of MNV between groups were compared. Independent samples t-test or Mann-Whitney U test was used for between-group comparisons; a multivariate regression model was established to analyze independent factors affecting SHRM signal characteristics. Results:Among the 46 eyes of 46 patients, there were 26 eyes of 26 males (56.52%, 26/46) and 20 eyes of 20 females (43.48%, 20/26). The mean age was (65.61±7.50) years. The average vessel length and vessel dispersion in the high-density SHRM group and low-density SHRM group were (6.88±4.56), (11.30±6.31) mm ?1 and 41.30±67.26, 13.22±11.34, respectively. Compared with the low-density SHRM group, the high-density SHRM group had significantly lower average vessel length ( t=2.645) and higher vessel dispersion ( t=?2.090), with statistically significant differences ( P=0.012, 0.046). Compared with the homogeneous SHRM group, the non-homogeneous SHRM group had significantly higher total area ( t=?2.338), maximum diameter ( t=?3.137), and minimum diameter ( t=?2.173), with statistically significant differences ( P<0.05). The total number of vascular network junctions in the non-homogeneous SHRM group and homogeneous SHRM group were (90.71±67.34) and (49.34±41.91), respectively; the non-homogeneous SHRM group had significantly more junctions than the homogeneous SHRM group, with a statistically significant difference ( t=?2.286, P=0.032). Multivariate regression analysis showed that average vessel length was an independent factor affecting SHRM intensity (odds ratio=0.819, 95% confidence interval 0.705-0.951, P=0.009); there were no independent vascular indicators affecting SHRM reflectivity homogeneity ( P>0.05). Conclusion:In nAMD, compared with low-density SHRM, high-density SHRM has significantly lower average vessel length and higher vessel dispersion; compared with homogeneous SHRM, non-homogeneous SHRM has a larger spatial dimension of the vascular network.
2.Correlation analysis of signal characteristics of subretinal hyperreflective material and neovascular morphology in neovascular age-related macular degeneration
Jiaxin PU ; Yuying JI ; Xuenan ZHUANG ; Xinlei HAO ; Feng WEN
Chinese Journal of Ocular Fundus Diseases 2025;41(8):605-612
Objective:To observe the signal intensity and homogeneity of subretinal hyperreflective material (SHRM) in neovascular age-related macular degeneration (nAMD) and preliminarily analyze its relationship with macular neovascularization (MNV) morphology.Methods:A prospective cross-sectional observational study. Forty-six eyes of 46 nAMD patients with SHRM who initially visited Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 2022 to March 31, 2023 were enrolled. Optical coherence tomography (OCT) examination was performed according to a standardized protocol, and 3D Slicer software was used for three-dimensional reconstruction of SHRM lesions. Signal intensity was represented by the mean gray value (mGV) of the three-dimensional lesion area, and homogeneity was represented by the standard deviation of gray values (GV-SD). OCT angiography (OCTA) was used to scan the 6 mm×6 mm area of the macula. FIJI and Angio Tool software were used to measure MNV vascular network total area, perimeter, maximum and minimum diameters, maximum vessel diameter, vascular component area, total number of vascular network junctions and endpoints, vessel dispersion, and mean lacunarity. The ratio of maximum to minimum diameter of the vascular network, average vessel length, vessel density, and vessel fractal index were calculated. Using the mean mGV of the total sample as the standard, the eyes were divided into low-density SHRM group (20 eyes) and high-density SHRM group (26 eyes); using the mean GV-SD of the total sample as the standard, the eyes were divided into homogeneous SHRM group (29 eyes) and non-homogeneous SHRM group (17 eyes). The morphological characteristics of MNV between groups were compared. Independent samples t-test or Mann-Whitney U test was used for between-group comparisons; a multivariate regression model was established to analyze independent factors affecting SHRM signal characteristics. Results:Among the 46 eyes of 46 patients, there were 26 eyes of 26 males (56.52%, 26/46) and 20 eyes of 20 females (43.48%, 20/26). The mean age was (65.61±7.50) years. The average vessel length and vessel dispersion in the high-density SHRM group and low-density SHRM group were (6.88±4.56), (11.30±6.31) mm ?1 and 41.30±67.26, 13.22±11.34, respectively. Compared with the low-density SHRM group, the high-density SHRM group had significantly lower average vessel length ( t=2.645) and higher vessel dispersion ( t=?2.090), with statistically significant differences ( P=0.012, 0.046). Compared with the homogeneous SHRM group, the non-homogeneous SHRM group had significantly higher total area ( t=?2.338), maximum diameter ( t=?3.137), and minimum diameter ( t=?2.173), with statistically significant differences ( P<0.05). The total number of vascular network junctions in the non-homogeneous SHRM group and homogeneous SHRM group were (90.71±67.34) and (49.34±41.91), respectively; the non-homogeneous SHRM group had significantly more junctions than the homogeneous SHRM group, with a statistically significant difference ( t=?2.286, P=0.032). Multivariate regression analysis showed that average vessel length was an independent factor affecting SHRM intensity (odds ratio=0.819, 95% confidence interval 0.705-0.951, P=0.009); there were no independent vascular indicators affecting SHRM reflectivity homogeneity ( P>0.05). Conclusion:In nAMD, compared with low-density SHRM, high-density SHRM has significantly lower average vessel length and higher vessel dispersion; compared with homogeneous SHRM, non-homogeneous SHRM has a larger spatial dimension of the vascular network.
3.Study on the mechanism of Lycium barbarum polysaccharide on reproductive toxicity induced by sevoflurane anesthesia in male rats based on ERK/Nrf2-ARE pathway
Ying SUN ; Zhuang LIU ; Xuenan WANG
Chinese Journal of Reproduction and Contraception 2023;43(8):806-812
Objective:To explore the effect of Lycium barbarum polysaccharide (LBP) on sevoflurane anesthesia-induced reproductive toxicity in male rats, and to analyze its effect on extracellular signal-regulated kinase (ERK)/nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway.Methods:SD male rats were randomly divided into blank control group, model group, low-dose LBP group, high-dose LBP group and positive control group. Except for the blank control group, the rest were induced by sevoflurane anesthesia and administered by intraperitoneal injection at the same time. The model group was given equal volume of normal saline; the LBP low- and high-dose groups were given 100 mg/kg and 200 mg/kg LBP, once a day, respectively. The positive control group was given 10 mg/kg vitamin E, once every other day. After 14 d of the experiment, all rats were sacrificed. The organ indexes of testis and epididymis of rats in each group were calculated. The contents of testis tissue marker enzymes acid phosphatase (ACP), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) were detected. HE staining was used to observe the testicular tissue disease of rats. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in testis tissue were detected. TUNEL staining was used to observe the apoptosis rate of rat testis tissue. Western blotting was used to detect Bax, Bcl-2 and ERK/Nrf2-ARE pathway protein expression level.Results:In the low-dose and high-dose LBP groups and positive control group, the testicles [(0.39±0.04)%, (0.47±0.05)%, (0.62±0.05)%] and epididymal organ index [(0.08±0.01)%, (0.11±0.01)%, (0.14±0.02)%] were higher than those of the model group [(0.33±0.03)%, (0.05±0.01)%, all P<0.001], ACP [(122.13±5.39) U/g, (115.37±4.45) U/g, (109.74±4.73) U/g] and LDH content [(260.43±15.18) U/g, (245.17±8.13) U/g, (236.19±10.23) U/g] were lower than those in the model group [(129.98±6.17) U/g, (279.89±18.41) U/g, all P<0.001], the AKP content [(224.41±11.69) U/g, (247.59±12.17) U/g, (266.74±13.78) U/g] and SOD activity [(3.11±0.12) U·mg/protein, (4.05±0.14) U·mg/protein, (4.78±0.15) U·mg/protein] were higher than those in the model group [(200.48±10.48) U/g, (2.02±0.09) U·mg/protein, all P<0.001], MDA content [(14.86±1.41) nmol·mg/protein, (10.39±1.22) nmol·mg/protein, (5.25±0.47) nmol·mg/protein] was lower than that in the model group [(18.36±1.99) nmol·mg/protein, all P<0.001], the apoptosis rate of testicular cells was relatively low (all P<0.001) and showed a LBP dose-dependent relationship (all P<0.001). The seminiferous tubule of the model group became thinner, and spermatid were significantly reduced, and only a small amount of spermatogonium remained in some seminiferous tubules. After administration, the structure of seminiferous tubule in the low- and high-dose LBP groups and the positive control group was relatively complete, and spermatid at all levels were arranged in order, the number increased, and vacuoles decreased. The levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 proteins in the testicular tissue of the model group were higher than those of the blank control group, while the levels of Bax protein were lower than those of the blank control group (all P<0.05), the protein levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 in the low- and high-dose LBP groups were higher than those in the model group, while the protein levels of Bax were lower than that in the model group (all P<0.05), and showed a LBP dose-dependent (all P<0.05). Conclusion:LBP has an antagonistic effect on sevoflurane anesthesia-induced reproductive toxicity in male rats, which may be related to the inhibition of ERK/Nrf2-ARE pathway.
4.Study on the mechanism of Lycium barbarum polysaccharide on reproductive toxicity induced by sevoflurane anesthesia in male rats based on ERK/Nrf2-ARE pathway
Ying SUN ; Zhuang LIU ; Xuenan WANG
Chinese Journal of Reproduction and Contraception 2023;43(8):806-812
Objective:To explore the effect of Lycium barbarum polysaccharide (LBP) on sevoflurane anesthesia-induced reproductive toxicity in male rats, and to analyze its effect on extracellular signal-regulated kinase (ERK)/nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway.Methods:SD male rats were randomly divided into blank control group, model group, low-dose LBP group, high-dose LBP group and positive control group. Except for the blank control group, the rest were induced by sevoflurane anesthesia and administered by intraperitoneal injection at the same time. The model group was given equal volume of normal saline; the LBP low- and high-dose groups were given 100 mg/kg and 200 mg/kg LBP, once a day, respectively. The positive control group was given 10 mg/kg vitamin E, once every other day. After 14 d of the experiment, all rats were sacrificed. The organ indexes of testis and epididymis of rats in each group were calculated. The contents of testis tissue marker enzymes acid phosphatase (ACP), alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) were detected. HE staining was used to observe the testicular tissue disease of rats. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in testis tissue were detected. TUNEL staining was used to observe the apoptosis rate of rat testis tissue. Western blotting was used to detect Bax, Bcl-2 and ERK/Nrf2-ARE pathway protein expression level.Results:In the low-dose and high-dose LBP groups and positive control group, the testicles [(0.39±0.04)%, (0.47±0.05)%, (0.62±0.05)%] and epididymal organ index [(0.08±0.01)%, (0.11±0.01)%, (0.14±0.02)%] were higher than those of the model group [(0.33±0.03)%, (0.05±0.01)%, all P<0.001], ACP [(122.13±5.39) U/g, (115.37±4.45) U/g, (109.74±4.73) U/g] and LDH content [(260.43±15.18) U/g, (245.17±8.13) U/g, (236.19±10.23) U/g] were lower than those in the model group [(129.98±6.17) U/g, (279.89±18.41) U/g, all P<0.001], the AKP content [(224.41±11.69) U/g, (247.59±12.17) U/g, (266.74±13.78) U/g] and SOD activity [(3.11±0.12) U·mg/protein, (4.05±0.14) U·mg/protein, (4.78±0.15) U·mg/protein] were higher than those in the model group [(200.48±10.48) U/g, (2.02±0.09) U·mg/protein, all P<0.001], MDA content [(14.86±1.41) nmol·mg/protein, (10.39±1.22) nmol·mg/protein, (5.25±0.47) nmol·mg/protein] was lower than that in the model group [(18.36±1.99) nmol·mg/protein, all P<0.001], the apoptosis rate of testicular cells was relatively low (all P<0.001) and showed a LBP dose-dependent relationship (all P<0.001). The seminiferous tubule of the model group became thinner, and spermatid were significantly reduced, and only a small amount of spermatogonium remained in some seminiferous tubules. After administration, the structure of seminiferous tubule in the low- and high-dose LBP groups and the positive control group was relatively complete, and spermatid at all levels were arranged in order, the number increased, and vacuoles decreased. The levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 proteins in the testicular tissue of the model group were higher than those of the blank control group, while the levels of Bax protein were lower than those of the blank control group (all P<0.05), the protein levels of Bcl-2, p-ERK1/2, Nrf2, HO-1, and NQO1 in the low- and high-dose LBP groups were higher than those in the model group, while the protein levels of Bax were lower than that in the model group (all P<0.05), and showed a LBP dose-dependent (all P<0.05). Conclusion:LBP has an antagonistic effect on sevoflurane anesthesia-induced reproductive toxicity in male rats, which may be related to the inhibition of ERK/Nrf2-ARE pathway.
5.Systemic factors associated with treatment response in patients with diabetic macular edema
Jie YAO ; Dan CAO ; Yunkao ZENG ; Xuenan ZHUANG ; Liang ZHANG
Chinese Journal of Ocular Fundus Diseases 2022;38(3):253-256
Diabetic macular edema (DME) is the main cause of vision loss and even blindness in patients with diabetic retinopathy. Intravitreal anti-vascular endothelial factor therapy has become the gold standard management of DME. However, not all eyes response optimally to common management of DME, which could be due to the differences of individual factors. Increasing age could be the predictive factors for poor outcome. The influence of glycemic control, hypertension, dyslipidemia, chronic kidney disease and relative factors on treatment response require further investigation. Identifying the systemic factors that influence the treatment response of DME can provide the evidence to predict the prognosis of DME, and improve the efficacy of clinical treatment.
6.Analysis of peripheral pathological features of diabetic retinopathy based on ultra-wide-angle fundus imaging
Xuenan ZHUANG ; Dan CAO ; Jie YAO ; Ruoyu CHEN ; Yesheng CHEN ; Zicheng WANG ; Liang ZHANG
Chinese Journal of Ocular Fundus Diseases 2021;37(7):523-527
Objective:To analyze the distribution characteristics of peripheral retinopathy in Chinese patients with diabetic retinopathy (DR).Methods:A cross-sectional study. From January to December 2019, 265 cases of 388 eyes of DR patients diagnosed in the eye examination of Guangdong Provincial People's Hospital were included in the study. Among them, there were 211 eyes in 148 males and 177 eyes in 117 females; the average age was 58.4±12.3 years. Ultra-wide-angle fundus imaging (UWF) examination was performed by Daytona in Aalborg, UK. Use Photoshop to simulate the standard 7-azimuth (S7F) area, which was used as the central retinal area 1-7. The peripheral retinal areas 3-7 (P3-P7) were the adjacent peripheral retinal areas of the central retinal area 3-7, respectively. Divided DR into peripheral lesion predominant type (PPL) and central lesion predominant type (PCL). PPL was defined as at least one peripheral retinal area with more severe disease than its adjacent central area. χ 2 test was performed on the difference of PPL composition ratio in each retinal area of eyes with different DR stages. Results:Among 388 eyes, 200 eyes were PPL (51.5%, 200/388). Compared of PPL composition ratios of eyes with different stages of DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR were 32 (36.8%, 32/87), 89 (55.3%, 89/161)), 42 (51.9%, 42/81), 37 (62.6%, 37/59), the difference was statistically significant ( χ2=11.440, P=0.010). Comparison of the distribution of PPL in each retinal area in DR eyes: in 200 PPL eyes, areas 3, 4, 5, 6, and 7 have 87, 101, 78, 67, and 38 eyes, respectively. The distribution of PPL in each retinal area in DR eyes was compared, and the difference was statistically significant ( χ2=37.640, P<0.001). Conclusions:PPL accounts for 51.5% of the eyes with DR. The DR stage are more severe, the proportion of PPL is higher. The temporal retinal peripheral lesions are the most common.
7.Changes of macular vessel density and structures in different early stages of diabetic retinopathy
Yunkao ZENG ; Dawei YANG ; Dan CAO ; Honghua YU ; Manhong LU ; Xuenan ZHUANG ; Liang ZHANG
Chinese Journal of Experimental Ophthalmology 2020;38(9):783-787
Objective:To investigate the characteristics of macular perfusion and structures in patients with early stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).Methods:A cross-sectional study was performed.Forty eyes of 27 diabetic patients without diabetic retinopathy (NDR), forty eyes of 24 patients with mild non-proliferative diabetic retinopathy (NPDR) and forty eyes of 28 patients with moderate NPDR were recruited in Guangdong Provincial People's Hospital from June 2017 to August 2018.RTVue-XR OCTA was used to scan a 6 mm×6 mm area centered in the fovea and the superficial vascular complex (SVC) and deep vascular complex (DVC) vessel density, fovea avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), and vessel density of a 300 μm wide ring area around FAZ (FD300) were quantified.The associations among stages of DR and macular vessel density, structures were analyzed.This study was approved by the Ethics Committee of the Guangdong Provincial People's Hospital (No.2016232A).Results:The vessel density of SVC and DVC tended to decrease as the progression of DR.The vessel density of SVC was (51.25±3.27)%, (48.81±3.99)%, (47.00±3.49)%, (45.73±3.35)%, and the vessel density of DVC was (53.89±6.30)%, (49.94±6.05)%, (46.69±4.87)% and (44.78±4.30)% in the control group, NDR group, mild NPDR group, and moderate NPDR group, respectively.The vessel densities of SVC and DVC were statistically different among the four groups ( F=18.33, 21.53; both at P<0.01). The vessel density of SVC and DVC in the NDR group, mild NPDR group, moderate NPDR group was significantly lower than that in the control group (all at P<0.01). The vessel densities of FD300 in the mild NPDR group and moderate NPDR group were significantly lower than that in the control group (all at P<0.01). The FAZ area of the control group, NDR group, mild NPDR group, and moderate NPDR group was (0.31±0.11), (0.32±0.09), (0.34±0.13), and (0.37±0.10)mm 2, respectively.There was no significant difference in the FAZ area among the four groups ( F=2.18, P=0.09). The FAZ perimeter and AI were significantly higher in the moderate NPDR group than those in the control group (both at P<0.05). Conclusions:OCTA is able to detect the decrease of vessel density in diabetic patients before the occurrence of visible fundus lesions.The vessel density of SVC and DVC in patients with early stages of DR is decreased.DVC vessel density may be a sensitive marker to indicate DR.FD300 is not significantly decreased until mild NPDR, FAZ area and perimeter are significantly increased in moderate NPDR, indicating a more irregular FAZ.

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