Background: To compare the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal of mCNV around the perforating scleral vessel (PSV).
Methods: A consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The neovascular signal relationship between PSV and mCNV were classified into the presence of neovascular signal of CNV around PSV or not. The recurrence of mCNV, best-corrected visual acuity (BCVA), hyperreflective foci height, CNV area and CNV flow area were analyzed between two groups.
Results: Neovascular signal of CNV around PSV was detected in 20 eyes (39.2%). The one-year recurrence rate in the group with neovascular signal of CNV around PSV was significantly higher than that in the group without neovascular signal of CNV around PSV (P = 0.045). The recurrence time in the group with neovascular signal around PSV was shorter than that in the group without neovascular signal around PSV (P = 0.030). Cox proportional hazard model showed that the presence of neovascular signal of CNV around PSV [hazard ratio (HR): 2.904] and subfoveal choroidal thickness ≤ 50 μm (HR: 0.368) were risk factors for recurrence of mCNV. In the group with neovascular signal around PSV, the BCVA was worse (P = 0.024) and the CNV flow area was more unstable (P = 0.027) after therapy.
Conclusions: PSV was commonly detected in patients with mCNV. The presence of neovascular signal of CNV around PSV was prone to recur with a shorter time in mCNV patients.
{"title":"Myopic choroidal neovascularization with neovascular signal around perforating scleral vessel prone to recur after anti-VEGF therapy.","authors":"Xiangjun She, Wangjing Yao, Gongyu Huang, Zhi Liang, Jin Xie, Jiwei Tao, Sulan Wu, Jianbo Mao, Yiqi Chen, Yun Zhang, Lijun Shen","doi":"10.1186/s40662-024-00374-5","DOIUrl":"10.1186/s40662-024-00374-5","url":null,"abstract":"<p><strong>Background: </strong>To compare the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal of mCNV around the perforating scleral vessel (PSV).</p><p><strong>Methods: </strong>A consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The neovascular signal relationship between PSV and mCNV were classified into the presence of neovascular signal of CNV around PSV or not. The recurrence of mCNV, best-corrected visual acuity (BCVA), hyperreflective foci height, CNV area and CNV flow area were analyzed between two groups.</p><p><strong>Results: </strong>Neovascular signal of CNV around PSV was detected in 20 eyes (39.2%). The one-year recurrence rate in the group with neovascular signal of CNV around PSV was significantly higher than that in the group without neovascular signal of CNV around PSV (P = 0.045). The recurrence time in the group with neovascular signal around PSV was shorter than that in the group without neovascular signal around PSV (P = 0.030). Cox proportional hazard model showed that the presence of neovascular signal of CNV around PSV [hazard ratio (HR): 2.904] and subfoveal choroidal thickness ≤ 50 μm (HR: 0.368) were risk factors for recurrence of mCNV. In the group with neovascular signal around PSV, the BCVA was worse (P = 0.024) and the CNV flow area was more unstable (P = 0.027) after therapy.</p><p><strong>Conclusions: </strong>PSV was commonly detected in patients with mCNV. The presence of neovascular signal of CNV around PSV was prone to recur with a shorter time in mCNV patients.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"11 1","pages":"6"},"PeriodicalIF":4.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1186/s40662-023-00372-z
Yong-Yeon Song, Hyun-Je Seong, Jung-Tae Kim, Sung-Chul Lee, Min-Woo Lee
Background: To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept.
Methods: Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups.
Results: A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm2 vs. 2.22 ± 2.26 µm2, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid.
Conclusions: Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.
{"title":"Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept.","authors":"Yong-Yeon Song, Hyun-Je Seong, Jung-Tae Kim, Sung-Chul Lee, Min-Woo Lee","doi":"10.1186/s40662-023-00372-z","DOIUrl":"10.1186/s40662-023-00372-z","url":null,"abstract":"<p><strong>Background: </strong>To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept.</p><p><strong>Methods: </strong>Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups.</p><p><strong>Results: </strong>A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm<sup>2</sup> vs. 2.22 ± 2.26 µm<sup>2</sup>, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid.</p><p><strong>Conclusions: </strong>Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"11 1","pages":"4"},"PeriodicalIF":4.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-16DOI: 10.1186/s40662-023-00362-1
Pooja Malaviya, Renu A. Kowluru
Diabetic retinopathy is a progressive disease, and one of the key metabolic abnormalities in the pathogenesis of diabetic retinopathy, mitochondrial damage, is also influenced by the duration of hyperglycemia. Mitochondrial quality control involves a coordination of mitochondrial dynamics, biogenesis and removal of the damaged mitochondria. In diabetes, these processes are impaired, and the damaged mitochondria continue to produce free radicals. Diabetic patients also have high homocysteine and reduced levels of hydrogen sulfide, and hyperhomocysteinemia is shown to exacerbate diabetes-induced mitochondrial damage and worsen their dynamics. This study aims to investigate the temporal relationship between hyperhomocysteinemia and retinal mitochondrial quality control in diabetic retinopathy. Human retinal endothelial cells incubated in 20 mM d-glucose for 24 to 96 h, in the absence or presence of 100 µM homocysteine, with/without a hydrogen sulfide donor GYY4137, were analyzed for mitochondrial ROS (MitoSox fluorescence), DNA damage (transcripts of mtDNA-encoded ND6 and CytB), copy numbers, oxygen consumption rate (Seahorse XF analyzer) and mitophagy (mitophagosomes immunofluorescence labeling and flow cytometry). Results were confirmed in the retina from mice genetically manipulated for hyperhomocysteinemia (cystathionine β-synthase deficient mice, Cbs+/−), streptozotocin-induced diabetic for 8 to 24 weeks. At 24 weeks of diabetes, vascular health was evaluated by counting acellular capillaries in the trypsin digested retinal vasculature and by fluorescein angiography. Homocysteine, in high glucose medium, exacerbated mitochondrial ROS production, mtDNA damage and impaired mitochondrial respiration within 24 h, and slowed down/worsened mitochondrial biogenesis and mitophagy, as compared to 48 to 96 h in high glucose alone. GYY4137 supplementation ameliorated homocysteine + high glucose-induced mitochondrial damage and impairment in biogenesis and mitophagy. Similar results were obtained from Cbs+/− mice-mitochondrial ROS, mtDNA damage and decline in biogenesis and mitophagy were observed within eight weeks of diabetes vs. 16 to 24 weeks of diabetes in Cbs+/+ mice, and at 24 weeks of diabetes, Cbs+/− mice had significantly higher acellular capillaries and vascular leakage. Hyperhomocysteinemia, in a hyperglycemic environment, overwhelms the mitochondria, accelerating and exacerbating their dysfunction, and also delays/worsens their removal, augmenting the development of diabetic retinopathy. Thus, our results strengthen the importance of maintaining homocysteine-hydrogen sulfide balance during the early stages of diabetes for a patient to prevent/retard vision loss.
{"title":"Homocysteine and mitochondrial quality control in diabetic retinopathy","authors":"Pooja Malaviya, Renu A. Kowluru","doi":"10.1186/s40662-023-00362-1","DOIUrl":"https://doi.org/10.1186/s40662-023-00362-1","url":null,"abstract":"Diabetic retinopathy is a progressive disease, and one of the key metabolic abnormalities in the pathogenesis of diabetic retinopathy, mitochondrial damage, is also influenced by the duration of hyperglycemia. Mitochondrial quality control involves a coordination of mitochondrial dynamics, biogenesis and removal of the damaged mitochondria. In diabetes, these processes are impaired, and the damaged mitochondria continue to produce free radicals. Diabetic patients also have high homocysteine and reduced levels of hydrogen sulfide, and hyperhomocysteinemia is shown to exacerbate diabetes-induced mitochondrial damage and worsen their dynamics. This study aims to investigate the temporal relationship between hyperhomocysteinemia and retinal mitochondrial quality control in diabetic retinopathy. Human retinal endothelial cells incubated in 20 mM d-glucose for 24 to 96 h, in the absence or presence of 100 µM homocysteine, with/without a hydrogen sulfide donor GYY4137, were analyzed for mitochondrial ROS (MitoSox fluorescence), DNA damage (transcripts of mtDNA-encoded ND6 and CytB), copy numbers, oxygen consumption rate (Seahorse XF analyzer) and mitophagy (mitophagosomes immunofluorescence labeling and flow cytometry). Results were confirmed in the retina from mice genetically manipulated for hyperhomocysteinemia (cystathionine β-synthase deficient mice, Cbs+/−), streptozotocin-induced diabetic for 8 to 24 weeks. At 24 weeks of diabetes, vascular health was evaluated by counting acellular capillaries in the trypsin digested retinal vasculature and by fluorescein angiography. Homocysteine, in high glucose medium, exacerbated mitochondrial ROS production, mtDNA damage and impaired mitochondrial respiration within 24 h, and slowed down/worsened mitochondrial biogenesis and mitophagy, as compared to 48 to 96 h in high glucose alone. GYY4137 supplementation ameliorated homocysteine + high glucose-induced mitochondrial damage and impairment in biogenesis and mitophagy. Similar results were obtained from Cbs+/− mice-mitochondrial ROS, mtDNA damage and decline in biogenesis and mitophagy were observed within eight weeks of diabetes vs. 16 to 24 weeks of diabetes in Cbs+/+ mice, and at 24 weeks of diabetes, Cbs+/− mice had significantly higher acellular capillaries and vascular leakage. Hyperhomocysteinemia, in a hyperglycemic environment, overwhelms the mitochondria, accelerating and exacerbating their dysfunction, and also delays/worsens their removal, augmenting the development of diabetic retinopathy. Thus, our results strengthen the importance of maintaining homocysteine-hydrogen sulfide balance during the early stages of diabetes for a patient to prevent/retard vision loss.","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"35 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139476833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-03DOI: 10.1186/s40662-023-00370-1
Danling Liao, Shijia Wei, Jianzhang Hu
Autophagy has recently been shown to be critical for protecting peripheral nerve regeneration. This study explored the impact of miR-542-3p on diabetic corneal nerve regeneration and epithelial healing through the regulation of autophagy. A type 1 diabetes model was established in male mice through streptozotocin administration. Immunofluorescence staining of β-Tubulin III and sodium fluorescein staining were performed to observe corneal nerve fiber density and corneal epithelial healing, respectively. Western blotting, immunofluorescence and transmission electron microscopy were used to determine autophagy levels. Subconjunctival injection of RAPA and 3-MA altered autophagy levels; with them, we evaluated the role of autophagy in diabetic keratopathy. miRNA sequencing and bioinformatics analysis were performed to identify miRNA-mRNA networks with potential autophagy-regulating roles, and miR-542-3p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). miR-542-3p antagomir was injected subconjunctivally to assess the role in diabetic corneal neuropathy. Our data suggest that autophagy is suppressed in the diabetic corneal nerve and that activation of autophagy promotes diabetic corneal wound healing. We identified a potential autophagy-regulating miRNA-mRNA network in the diabetic trigeminal ganglion, in which miR-542-3p expression was significantly upregulated. Inhibition of miR-542-3p significantly enhanced the level of autophagy in trigeminal ganglion by upregulating ATG4D expression, thereby accelerating diabetic corneal nerve regeneration and epithelial healing. Dysregulated autophagy is an important contributor to delayed diabetic corneal injury healing. Inhibiting miR-542-3p promotes diabetic corneal nerve regeneration and epithelial healing through autophagy activation by ATG4D.
{"title":"Inhibition of miR-542-3p augments autophagy to promote diabetic corneal wound healing","authors":"Danling Liao, Shijia Wei, Jianzhang Hu","doi":"10.1186/s40662-023-00370-1","DOIUrl":"https://doi.org/10.1186/s40662-023-00370-1","url":null,"abstract":"Autophagy has recently been shown to be critical for protecting peripheral nerve regeneration. This study explored the impact of miR-542-3p on diabetic corneal nerve regeneration and epithelial healing through the regulation of autophagy. A type 1 diabetes model was established in male mice through streptozotocin administration. Immunofluorescence staining of β-Tubulin III and sodium fluorescein staining were performed to observe corneal nerve fiber density and corneal epithelial healing, respectively. Western blotting, immunofluorescence and transmission electron microscopy were used to determine autophagy levels. Subconjunctival injection of RAPA and 3-MA altered autophagy levels; with them, we evaluated the role of autophagy in diabetic keratopathy. miRNA sequencing and bioinformatics analysis were performed to identify miRNA-mRNA networks with potential autophagy-regulating roles, and miR-542-3p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). miR-542-3p antagomir was injected subconjunctivally to assess the role in diabetic corneal neuropathy. Our data suggest that autophagy is suppressed in the diabetic corneal nerve and that activation of autophagy promotes diabetic corneal wound healing. We identified a potential autophagy-regulating miRNA-mRNA network in the diabetic trigeminal ganglion, in which miR-542-3p expression was significantly upregulated. Inhibition of miR-542-3p significantly enhanced the level of autophagy in trigeminal ganglion by upregulating ATG4D expression, thereby accelerating diabetic corneal nerve regeneration and epithelial healing. Dysregulated autophagy is an important contributor to delayed diabetic corneal injury healing. Inhibiting miR-542-3p promotes diabetic corneal nerve regeneration and epithelial healing through autophagy activation by ATG4D.","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"1 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139082059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-03DOI: 10.1186/s40662-023-00371-0
Phillip T. Yuhas, Maddison M. Fortman, Ashraf M. Mahmoud, Cynthia J. Roberts
Keratoconus is characterized by asymmetry in the biomechanical properties of the cornea, with focal weakness in the area of cone formation. We tested the hypothesis that centrally-measured biomechanical parameters differ between corneas with peripheral cones and corneas with central cones. Fifty participants with keratoconus were prospectively recruited. The mean ± standard deviation age was 38 ± 13 years. Axial and tangential corneal topography were analyzed in both eyes, if eligible. Cones in the central 3 mm of the cornea were considered central, and cones outside the central 3 mm were considered peripheral. Each eye was then measured with the Ocular Response Analyzer (ORA) tonometer. T-tests compared differences in ORA-generated waveform parameters between cohorts. Seventy-eight eyes were analyzed. According to the axial topography maps, 37 eyes had central cones and 41 eyes had peripheral cones. According to the tangential topography maps, 53 eyes had central cones, and 25 eyes had peripheral cones. For the axial-topography algorithm, wave score (WS) was significantly higher in peripheral cones than central cones (inter-cohort difference = 1.27 ± 1.87). Peripheral cones had a significantly higher area of first peak, p1area (1047 ± 1346), area of second peak, p2area (1130 ± 1478), height of first peak, h1 (102 ± 147), and height of second peak, h2 (102 ± 127), than central cones. Corneal hysteresis (CH), width of the first peak, w1, and width of the second peak, w2, did not significantly differ between cohorts. There were similar results for the tangential-topography algorithm, with a significant difference between the cohorts for p1area (855 ± 1389), p2area (860 ± 1531), h1 (81.7 ± 151), and h2 (92.1 ± 131). Cone location affects the biomechanical response parameters measured under central loading of the cornea. The ORA delivers its air puff to the central cornea, so the fact that h1 and h2 and that p1area and p2area were smaller in the central cone cohort than in the peripheral cone cohort suggests that corneas with central cones are softer or more compliant centrally than corneas with peripheral cones, which is consistent with the location of the pathology. This result is evidence that corneal weakening in keratoconus is focal in nature and is consistent with localized disruption of lamellar orientation.
{"title":"Keratoconus cone location influences ocular biomechanical parameters measured by the Ocular Response Analyzer","authors":"Phillip T. Yuhas, Maddison M. Fortman, Ashraf M. Mahmoud, Cynthia J. Roberts","doi":"10.1186/s40662-023-00371-0","DOIUrl":"https://doi.org/10.1186/s40662-023-00371-0","url":null,"abstract":"Keratoconus is characterized by asymmetry in the biomechanical properties of the cornea, with focal weakness in the area of cone formation. We tested the hypothesis that centrally-measured biomechanical parameters differ between corneas with peripheral cones and corneas with central cones. Fifty participants with keratoconus were prospectively recruited. The mean ± standard deviation age was 38 ± 13 years. Axial and tangential corneal topography were analyzed in both eyes, if eligible. Cones in the central 3 mm of the cornea were considered central, and cones outside the central 3 mm were considered peripheral. Each eye was then measured with the Ocular Response Analyzer (ORA) tonometer. T-tests compared differences in ORA-generated waveform parameters between cohorts. Seventy-eight eyes were analyzed. According to the axial topography maps, 37 eyes had central cones and 41 eyes had peripheral cones. According to the tangential topography maps, 53 eyes had central cones, and 25 eyes had peripheral cones. For the axial-topography algorithm, wave score (WS) was significantly higher in peripheral cones than central cones (inter-cohort difference = 1.27 ± 1.87). Peripheral cones had a significantly higher area of first peak, p1area (1047 ± 1346), area of second peak, p2area (1130 ± 1478), height of first peak, h1 (102 ± 147), and height of second peak, h2 (102 ± 127), than central cones. Corneal hysteresis (CH), width of the first peak, w1, and width of the second peak, w2, did not significantly differ between cohorts. There were similar results for the tangential-topography algorithm, with a significant difference between the cohorts for p1area (855 ± 1389), p2area (860 ± 1531), h1 (81.7 ± 151), and h2 (92.1 ± 131). Cone location affects the biomechanical response parameters measured under central loading of the cornea. The ORA delivers its air puff to the central cornea, so the fact that h1 and h2 and that p1area and p2area were smaller in the central cone cohort than in the peripheral cone cohort suggests that corneas with central cones are softer or more compliant centrally than corneas with peripheral cones, which is consistent with the location of the pathology. This result is evidence that corneal weakening in keratoconus is focal in nature and is consistent with localized disruption of lamellar orientation.","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"78 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139082438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression.
Methods: A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility.
Results: The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus.
Conclusions: This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.
{"title":"Assessing progression limits in different grades of keratoconus from a novel perspective: precision of measurements of the corneal epithelium.","authors":"Rui Ning, Yiran Wang, Zhenyu Xu, Ingemar Gustafsson, Jiawei Li, Giacomo Savini, Domenico Schiano-Lomoriello, Yichen Xiao, Aodong Chen, Xiaoying Wang, Xingtao Zhou, Jinhai Huang","doi":"10.1186/s40662-023-00368-9","DOIUrl":"10.1186/s40662-023-00368-9","url":null,"abstract":"<p><strong>Background: </strong>To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression.</p><p><strong>Methods: </strong>A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (S<sub>w</sub>), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility.</p><p><strong>Results: </strong>The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus.</p><p><strong>Conclusions: </strong>This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"11 1","pages":"1"},"PeriodicalIF":4.2,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.1186/s40662-023-00369-8
Pascal Aurel Gubser, Valentin Pfeiffer, Simon Hug, Xiao Shang, Joel-Benjamin Lincke, Nathanael Urs Häner, Martin S. Zinkernagel, Jan Darius Unterlauft
To compare the intermediate-term efficacy of PRESERFLO (PF) MicroShunt implantation with trabeculectomy (TE) in patients with primary open-angle glaucoma, focusing on longitudinal changes of functional and structural parameters. This retrospective comparative study included 104 eyes of 104 patients who underwent TE and 83 eyes of 83 patients that underwent PF implantation between January 2019 and December 2020, with a minimum follow-up of two years. Baseline and postoperative intraocular pressure (IOP), number of IOP-lowering medications, visual field mean defect (MD) and peripapillary retinal nerve fibre layer (RNFL) thickness measured using optical coherence tomography were assessed and compared between groups. Baseline characteristics (age, sex, IOP, number of IOP-lowering medications, MD, RNFL thickness) were comparable between the two groups (all P > 0.05). During the two-year of follow-up, mean IOP decreased from 24.09 ± 1.15 mmHg and 21.67 ± 0.77 mmHg to 11.37 ± 1.13 mmHg (P < 0.001) and 15.50 ± 1.54 mmHg (P = 0.028), and the mean number of IOP-lowering medications decreased from 3.25 ± 0.14 and 3.51 ± 0.14 to 0.53 ± 0.14 (P < 0.001) and 1.06 ± 0.43 (P < 0.001) in the TE and PF groups, respectively. MD remained stable [− 11.54 ± 0.93 dB and − 11.17 ± 1.66 to − 10.67 ± 0.91 dB (P = 0.226) and − 10.40 ± 4.75 dB (P = 0.628) in the TE and PF groups, respectively] but RNFL thickness decreased continuously during follow-up [62.79 ± 1.94 µm and 62.62 ± 2.05 µm to 57.41 ± 1.81 µm (P < 0.001) and 60.22 ± 1.98 µm (P = 0.182) in the TE and PF groups, respectively]. PF implantation is comparably effective in the intermediate term in lowering IOP and reducing the use of IOP-lowering medications over a two-year follow-up period. Although visual field defects were stable, RNFL continued to decrease during postoperative follow-up.
{"title":"PRESERFLO MicroShunt implantation versus trabeculectomy for primary open-angle glaucoma: a two-year follow-up study","authors":"Pascal Aurel Gubser, Valentin Pfeiffer, Simon Hug, Xiao Shang, Joel-Benjamin Lincke, Nathanael Urs Häner, Martin S. Zinkernagel, Jan Darius Unterlauft","doi":"10.1186/s40662-023-00369-8","DOIUrl":"https://doi.org/10.1186/s40662-023-00369-8","url":null,"abstract":"To compare the intermediate-term efficacy of PRESERFLO (PF) MicroShunt implantation with trabeculectomy (TE) in patients with primary open-angle glaucoma, focusing on longitudinal changes of functional and structural parameters. This retrospective comparative study included 104 eyes of 104 patients who underwent TE and 83 eyes of 83 patients that underwent PF implantation between January 2019 and December 2020, with a minimum follow-up of two years. Baseline and postoperative intraocular pressure (IOP), number of IOP-lowering medications, visual field mean defect (MD) and peripapillary retinal nerve fibre layer (RNFL) thickness measured using optical coherence tomography were assessed and compared between groups. Baseline characteristics (age, sex, IOP, number of IOP-lowering medications, MD, RNFL thickness) were comparable between the two groups (all P > 0.05). During the two-year of follow-up, mean IOP decreased from 24.09 ± 1.15 mmHg and 21.67 ± 0.77 mmHg to 11.37 ± 1.13 mmHg (P < 0.001) and 15.50 ± 1.54 mmHg (P = 0.028), and the mean number of IOP-lowering medications decreased from 3.25 ± 0.14 and 3.51 ± 0.14 to 0.53 ± 0.14 (P < 0.001) and 1.06 ± 0.43 (P < 0.001) in the TE and PF groups, respectively. MD remained stable [− 11.54 ± 0.93 dB and − 11.17 ± 1.66 to − 10.67 ± 0.91 dB (P = 0.226) and − 10.40 ± 4.75 dB (P = 0.628) in the TE and PF groups, respectively] but RNFL thickness decreased continuously during follow-up [62.79 ± 1.94 µm and 62.62 ± 2.05 µm to 57.41 ± 1.81 µm (P < 0.001) and 60.22 ± 1.98 µm (P = 0.182) in the TE and PF groups, respectively]. PF implantation is comparably effective in the intermediate term in lowering IOP and reducing the use of IOP-lowering medications over a two-year follow-up period. Although visual field defects were stable, RNFL continued to decrease during postoperative follow-up.","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"32 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12DOI: 10.1186/s40662-023-00367-w
Grzegorz Łabuz, Helin Güngör, Gerd U. Auffarth, Timur M. Yildirim, Ramin Khoramnia
Chromatic aberration of the eye results from the dispersion of polychromatic light at the interfaces of ocular media. An intraocular lens (IOL) based approach utilizing the diffractive-multifocal principle has been proposed for its correction, but the clinical evidence on the impact of reducing or increasing chromatic aberration on the visual quality of pseudophakic patients remains scarce. In this cross-sectional study, longitudinal chromatic aberration (LCA) effects were studied monocularly in 37 patients implanted with a monofocal lens. LogMAR corrected distance visual acuity (VA) and defocus curve at the + 1.0 D to − 2.0 D range were assessed. Contrast sensitivity (CS) was evaluated at far and at four spatial frequencies. Measurements were performed with the eye's natural conditions, as well as with increased and corrected (by the same amount) LCA, which was altered by introducing zero-power trial triplets. The mean (± standard deviation) logMAR VA was − 0.11 ± 0.07 for the natural condition, − 0.13 ± 0.07 for the LCA-corrected eye, and − 0.06 ± 0.08 for the eye with increased LCA. A sharp decline of the defocus tolerance was found after the LCA correction with the VA value of 0.38 ± 0.15 logMAR at − 1.5 D. However, for the natural and increased LCA, it was 0.32 ± 0.16 logMAR and 0.25 ± 0.13 logMAR, respectively. CS was improved at all spatial frequencies after the LCA correction, which was closely followed by the natural-eye performance. Increased LCA resulted in reduced CS, mainly at higher spatial frequencies. We demonstrated that elevating chromatic aberration above the natural level of monofocal patients extends their depth of focus while causing a measurable albeit minimal reduction in visual function. Still, the observed changes indicate that neither correction nor increase of LCA yields a substantial clinical effect on distance VA and CS in monofocal pseudophakia.
{"title":"Altering chromatic aberration: how this latest trend in intraocular-lens design affects visual quality in pseudophakic patients","authors":"Grzegorz Łabuz, Helin Güngör, Gerd U. Auffarth, Timur M. Yildirim, Ramin Khoramnia","doi":"10.1186/s40662-023-00367-w","DOIUrl":"https://doi.org/10.1186/s40662-023-00367-w","url":null,"abstract":"Chromatic aberration of the eye results from the dispersion of polychromatic light at the interfaces of ocular media. An intraocular lens (IOL) based approach utilizing the diffractive-multifocal principle has been proposed for its correction, but the clinical evidence on the impact of reducing or increasing chromatic aberration on the visual quality of pseudophakic patients remains scarce. In this cross-sectional study, longitudinal chromatic aberration (LCA) effects were studied monocularly in 37 patients implanted with a monofocal lens. LogMAR corrected distance visual acuity (VA) and defocus curve at the + 1.0 D to − 2.0 D range were assessed. Contrast sensitivity (CS) was evaluated at far and at four spatial frequencies. Measurements were performed with the eye's natural conditions, as well as with increased and corrected (by the same amount) LCA, which was altered by introducing zero-power trial triplets. The mean (± standard deviation) logMAR VA was − 0.11 ± 0.07 for the natural condition, − 0.13 ± 0.07 for the LCA-corrected eye, and − 0.06 ± 0.08 for the eye with increased LCA. A sharp decline of the defocus tolerance was found after the LCA correction with the VA value of 0.38 ± 0.15 logMAR at − 1.5 D. However, for the natural and increased LCA, it was 0.32 ± 0.16 logMAR and 0.25 ± 0.13 logMAR, respectively. CS was improved at all spatial frequencies after the LCA correction, which was closely followed by the natural-eye performance. Increased LCA resulted in reduced CS, mainly at higher spatial frequencies. We demonstrated that elevating chromatic aberration above the natural level of monofocal patients extends their depth of focus while causing a measurable albeit minimal reduction in visual function. Still, the observed changes indicate that neither correction nor increase of LCA yields a substantial clinical effect on distance VA and CS in monofocal pseudophakia.","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"470 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1186/s40662-023-00366-x
Fernando Mayordomo-Cerdá, Julio Ortega-Usobiaga, Julio Baviera-Sabater, Rafael Bilbao-Calabuig, Fernando Llovet-Osuna, Vasyl Druchkiv, Rosario Cobo-Soriano
Background: To assess whether a trifocal intraocular lens (IOL) with neutral spherical aberration (SA) provides better visual and refractive outcomes than a trifocal IOL with negative SA after hyperopic corneal laser ablation.
Methods: This is a retrospective comparative study. Patients were classified according to the IOL implanted after cataract or clear lens phacoemulsification [group 1, PhysIOL FineVision Pod-F (negative SA); group 2, Rayner RayOne Trifocal (neutral SA)]. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction.
Results: 198 eyes of 119 patients met the inclusion criteria. Group 1 comprised 120 eyes and group 2 comprised 78 eyes. At completion, the refractive and predictability results were significantly better in group 1 than in group 2 for manifest refraction spherical equivalent (MRSE) (P < 0.001). Differences were not significant for UDVA (P = 0.647), CDVA (P = 0.343), UIVA (P = 0.059), UNVA (P = 0.382), binocular UIVA (P = 0.157), or binocular UNVA (P = 0.527). Safety and efficacy indices in refractive lens exchange (RLE) eyes were 0.96 and 0.91, and 0.89 and 0.93 in groups 1 and 2, respectively (P = 0.254 and 0.168). Patient satisfaction was similar in both groups (P > 0.05, all items).
Conclusion: In eyes previously treated with hyperopic corneal ablation, implantation of a trifocal IOL with neutral SA provided better efficacy and safety outcomes but worse predictability outcomes than those obtained with a trifocal model with negative SA.
{"title":"Visual and refractive outcomes after implantation of two models of trifocal intraocular lenses in eyes with previous corneal ablation to treat hyperopia.","authors":"Fernando Mayordomo-Cerdá, Julio Ortega-Usobiaga, Julio Baviera-Sabater, Rafael Bilbao-Calabuig, Fernando Llovet-Osuna, Vasyl Druchkiv, Rosario Cobo-Soriano","doi":"10.1186/s40662-023-00366-x","DOIUrl":"10.1186/s40662-023-00366-x","url":null,"abstract":"<p><strong>Background: </strong>To assess whether a trifocal intraocular lens (IOL) with neutral spherical aberration (SA) provides better visual and refractive outcomes than a trifocal IOL with negative SA after hyperopic corneal laser ablation.</p><p><strong>Methods: </strong>This is a retrospective comparative study. Patients were classified according to the IOL implanted after cataract or clear lens phacoemulsification [group 1, PhysIOL FineVision Pod-F (negative SA); group 2, Rayner RayOne Trifocal (neutral SA)]. We evaluated uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), predictability, safety, efficacy, and satisfaction.</p><p><strong>Results: </strong>198 eyes of 119 patients met the inclusion criteria. Group 1 comprised 120 eyes and group 2 comprised 78 eyes. At completion, the refractive and predictability results were significantly better in group 1 than in group 2 for manifest refraction spherical equivalent (MRSE) (P < 0.001). Differences were not significant for UDVA (P = 0.647), CDVA (P = 0.343), UIVA (P = 0.059), UNVA (P = 0.382), binocular UIVA (P = 0.157), or binocular UNVA (P = 0.527). Safety and efficacy indices in refractive lens exchange (RLE) eyes were 0.96 and 0.91, and 0.89 and 0.93 in groups 1 and 2, respectively (P = 0.254 and 0.168). Patient satisfaction was similar in both groups (P > 0.05, all items).</p><p><strong>Conclusion: </strong>In eyes previously treated with hyperopic corneal ablation, implantation of a trifocal IOL with neutral SA provided better efficacy and safety outcomes but worse predictability outcomes than those obtained with a trifocal model with negative SA.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"10 1","pages":"48"},"PeriodicalIF":4.2,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10702098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1186/s40662-023-00365-y
Ashish Gupta, Daniel Ruminski, Alfonso Jimenez Villar, Raúl Duarte Toledo, Grzegorz Gondek, Barbara Pierscionek, Pablo Artal, Ireneusz Grulkowski
Background: The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function.
Methods: OCT images of the anterior segment of 49 eyes of subjects (9-78 years) were acquired, and the OSD zones (nucleus, C1-C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye's optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed.
Results: The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (- 0.053 mm/year, - 0.013 mm/year and - 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1β, and the highest increase in density was in the C2-C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function.
Conclusions: OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure-function relationship of the ageing lens and offer insights into both pathological and aging alterations.
{"title":"Age-related changes in geometry and transparency of human crystalline lens revealed by optical signal discontinuity zones in swept-source OCT images.","authors":"Ashish Gupta, Daniel Ruminski, Alfonso Jimenez Villar, Raúl Duarte Toledo, Grzegorz Gondek, Barbara Pierscionek, Pablo Artal, Ireneusz Grulkowski","doi":"10.1186/s40662-023-00365-y","DOIUrl":"10.1186/s40662-023-00365-y","url":null,"abstract":"<p><strong>Background: </strong>The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function.</p><p><strong>Methods: </strong>OCT images of the anterior segment of 49 eyes of subjects (9-78 years) were acquired, and the OSD zones (nucleus, C1-C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye's optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed.</p><p><strong>Results: </strong>The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (- 0.053 mm/year, - 0.013 mm/year and - 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1β, and the highest increase in density was in the C2-C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function.</p><p><strong>Conclusions: </strong>OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure-function relationship of the ageing lens and offer insights into both pathological and aging alterations.</p>","PeriodicalId":12194,"journal":{"name":"Eye and Vision","volume":"10 1","pages":"46"},"PeriodicalIF":4.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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