AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This mul...AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.展开更多
Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as ...Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.展开更多
●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A to...●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.展开更多
AIM:To analyze differences in ultra-widefield fluorescein angiography(UWFA)findings between dynamic and static images of eyes with diabetic retinopathy(DR).METHODS:This cross-sectional study included 28 eyes of 28 pat...AIM:To analyze differences in ultra-widefield fluorescein angiography(UWFA)findings between dynamic and static images of eyes with diabetic retinopathy(DR).METHODS:This cross-sectional study included 28 eyes of 28 patients with DR undergoing UWFA.A series of UWFA images acquired from each patient were converted into a time-lapse video and used as a dynamic image.A single,clear,arteriovenous phase image was chosen as a static image.Non-perfusion index(NPI)and its correlation with vascular abnormalities in different zones were compared between dynamic and static UWFA imaging.RESULTS:NPI appeared to increase from the center to the far-periphery in both groups.Dynamic NPI was lower in the total retinal area(0.26 vs 0.29,P=0.009)and farperiphery(0.33 vs 0.36,adjusted P=0.042),which was contrary to the static NPI.Far-peripheral NPI was associated with intraretinal microvascular abnormality in the posterior area in both groups.CONCLUSION:Time-lapse dynamic UWFA imaging is a useful modality to differentially diagnose hypofluorescence in the most peripheral region.This modality could provide a reliable method for NPI measurement.展开更多
In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alte...In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.展开更多
AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injecti...AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin.The retinas were harvested at 1 to 24 wk after diabetes onset.Hypoxia-treated mouse microglial cell line(BV2 cells)was employed as the in vitro model to mimic diabetic condition.The expressions of Iba-1,CD11 b,ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction,Western blot and immunofluorescence both in vivo and in vitro.RESULTS:Compared with age-matched normal control,the number of microglia(Iba-1 positive immunostaining)in diabetic rat retinas was increased from 1 to 24 wk of diabetes,which was most obvious at 12 wk of diabetes.Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control;however,there was statistically significant between two groups only at 2 wk after diabetes onset.The m RNA expression of Iba-1 was decreased significantly at 2 and 4 wk of diabetic rat retinas,and remained unchanged at 8 and 12 wk of diabetes.In BV2 cells,there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups;however,its m RNA level was decreased significantly under hypoxia.To further characterize microglial activation,F4/80,CD11 b and inflammatory factors were detected both in vivo and in vitro.Compared with normal control,the expressions of F4/80 and CD11 b as well as the inflammatory factors,such as ICAM-1,i NOS,COX2,IL-1βand IL-6,were increased significantly both in vivo and in vitro.CONCLUSION:Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR.However,Iba-1 immunostaining,in combination with other markers like CD11 b and ICAM-1,could be well reflect the activation of microglia.Thus,it is of great importance to explore other potential marker to evaluate the activation of microglia.展开更多
AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-por...AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-port pars plana vitrectomy was performed on 16 patients with high MF.A parallel arc line along the vascular arcades was scraped out with a curved membrane scraper DSP.Next,an ILM forceps was used to catch hold of the incisal edge of the ILM flap,and the action of releasing and separating was subsequently taken toward the direction of the macular fovea.Next,the ILM forceps was used to grasp the released area,and the whole area coherent ILM peeling covering the macular fovea was implemented thereafter.Finally,the ILM was folded backwards and peeled off in the arc direction.RESULTS:At the final visit,the average central macular thickness decreased remarkably from 423.76±177.67 to 178.24±66.21 μm.The mean logarithm of the minimum angle of resolution best-corrected visual acuity of 1.37±0.59 was significantly alleviated to 0.74±0.59.CONCLUSION:The wide range of whole piece consecutive ILM peeling without preservation of the epifovea is proven to be effective and significantly reduced the occurrence of retinal tear and macular hole.展开更多
Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more ...Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.展开更多
AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children...AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children were enrolled in this prospective clinical trial.Ninetyfive subjects in ortho-k group and eighty-eight subjects in spectacle group completed the 1-year study.Axial length(AL)was measured before enrollment and every 6mo after the start of ortho-k.The photopic pupil diameter(PPD)was determined using the Pentacam AXL and measured in an examination room with lighting of 300-310 Lx.Stepwise multiple linear regression analysis was used to identify variables contribution to axial elongation.RESULTS:Compared with spectacle group,the average 1-year axial elongation was significantly slower in the ortho-k group(0.25±0.27 vs 0.44±0.23 mm,P<0.0001).In ortho-k group,PPDs significantly decreased from 4.21±0.62 mm to 3.94±0.53 mm after 1mo of lens wear(P=0.001,Bonferroni correction)and the change lasts for 3-month visit.No significantly change during the other follow-up visits was found(P>0.05,Bonferroni correction).The 4.81 mm PPD may be a possible cutoff point in the ortho-k group.Subjects with PPD below or equal to 4.81 mm tended to have smaller axial elongation compared to subjects with PPD above 4.81 mm after 1-year period(t=-3.09,P=0.003).In ortho-k group,univariate analyses indicated that those with older age,greater degree of myopia,longer AL,smaller baseline PPD(PPDbaseline)experienced a smaller change in AL.In multivariate analyses,older age,greater AL and smaller PPDbaseline were associated with smaller increases in AL.In spectacle group,PPD tended to be stable(P>0.05,Bonferroni correction)and did not affect axial growth.CONCLUSION:PPDs experience significantly decreases at 1-month and 3-month ortho-k treatment.Children with smaller PPD tend to experience slower axial elongation and may benefit more from ortho-k.展开更多
AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twen...AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twenty-eight eyes from twenty-eight treatment-na?ve patients(14 males and 14 females) with RVO-ME were included in this retrospective study.The retinal vein occlusion(RVO) was comprised of both central retinal vein occlusion(CRVO,n=14) and branch retinal vein occlusion(BRVO,n=14).Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months,in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept.All eyes were imaged with optical coherence tomography angiography(OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection.The visual acuity(VA),central macular thickness(CMT),the number of hyperreflective foci(HRF) recognized as an inflammatory sign in OCT images,and non-perfusion area(NPA),were compared before and after anti-VEGF treatments.RESULTS: The mean interval between baseline and follow-up was 29.4±0.79(range,27-48)d.Compared with the baseline,the VA improved(log MAR 1.5±0.1 vs 0.8±0.1,P<0.05) and CMT decreased(460±34.0 μm vs 268.8±12.0 μm,P<0.05),significantly,after antiVEGF treatment.The number of HRF was decreased significantly(76.5±4.8 vs 47.8±4.3,P<0.05) after antiVEGF treatment.CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME.The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.展开更多
AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identi...AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and strategies.METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS.RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not(P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls(P>0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.展开更多
AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional table...AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera(Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR.RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range(1.47, 1.48, and 1.40) than conventional tabletop cameras(1.30, 1.28, and 1.18;P<0.001). Detection of retinal hemorrhage, hard exudation,and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1%(95%CI: 72.1%-92.2%) and 97.4%(95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory;however, Phoebus showed a high sensitivity(88.2%, 95%CI: 79.4%-97.1%) and low specificity(40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR.CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.展开更多
AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h...AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h ESRPE cells on two culture substrates,laminin521(LN-521)and truncated recombinant human vitronectin(VTN-N).METHODS:hES-RPE cells were used in the experiment.The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system.Quantitative real-time polymerase chain reaction was used to evaluate RPE-specific gene expression levels midway(day 10)and at the end(day 20)of the time course.Cell polarity was observed by immunofluorescent staining for apical and basal markers of the RPE.The phagocytic ability of hES-RPE cells was identified by flow cytometry and immunofluorescence.RESULTS:The cell adhesion assay showed that the ability of LN-521 to adhere to hES-RPE cells was dosedependent.With increasing coating concentration,an increasing number of cells attached to the surface of LN-521-coated wells.In contrast,VTN-N presented a strong adhesive ability even at a low concentration.The optimal concentration of LN-521 and VTN-N required to coat and adhesion to hES-RPE cells were 2 and 0.25μg/cm^(2),respectively.Furthermore,both LN-521 and VTN-N could facilitate adoption of the desired cobblestone cellular morphology with tight junction and showed polarity by the hES-RPE cells.However,hES-RPE cells cultivated in VTN-N had a greater phagocytic ability,and it took less time for these hES-RPE cells to mature.CONCLUSION:VTN-N is a more suitable coating substrate for cultivating hES-RPE cells.展开更多
AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroidassociated ophthalmopathy(TAO) could be an early sign to detect dysthyroid optic neuropathy(DON). METHODS: This...AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroidassociated ophthalmopathy(TAO) could be an early sign to detect dysthyroid optic neuropathy(DON). METHODS: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography(OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries(RPC), retinal nerve fiber layer(RNFL), and macular ganglion cell complex(GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. RESULTS: Whole choroidal RPC was significantly reduced in DON(48.24%±0.4978%) compared to normal(50.33%±0.3173%) and TAO without DON(49.16%±0.5463%;P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field(VF) defect in DON(r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed.CONCLUSION: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.展开更多
AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical cohe...AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was calculated.RESULTS: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.展开更多
Diabetic retinopathy(DR)is an important cause of blindness globally,and its prevalence is increasing.Early detection and intervention can help change the outcomes of the disease.The rapid development of artificial int...Diabetic retinopathy(DR)is an important cause of blindness globally,and its prevalence is increasing.Early detection and intervention can help change the outcomes of the disease.The rapid development of artificial intelligence(AI)in recent years has led to new possibilities for the screening and diagnosis of DR.An AI-based diagnostic system for the detection of DR has significant advantages,such as high efficiency,high accuracy,and lower demand for human resources.At the same time,there are shortcomings,such as the lack of standards for development and evaluation and the limited scope of application.This article demonstrates the current applications of AI in the field of DR,existing problems,and possible future development directions.展开更多
Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithe...Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithelial-mesenchymal transition(EMT)contribute to the fibrosis formation.N^(6)-Methyladenosine(m^(6)A)modification has been implicated in the EMT process and multiple fibrotic diseases.The role of m^(6)A modification in EMT-related subretinal fibrosis has not yet been elucidated.In this study,we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization,METTL3 was upregulated in RPE cells.Through m^(6)A epitranscriptomic microarray and further verification,high-mobility group AT-hook 2(HMGA2)was identified as thekey downstream target of METTL3,subsequently activating potent EMT-inducing transcription factor SNAIL.Finally,by subretinal injections of adeno-associated virus vectors,we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo.In conclusion,our present research identified an epigenetic mechanism of METTL3-m^(6)A-HMGA2 in subretinal fibrosis and EMT of RPE cells,providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.展开更多
Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprag...Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.展开更多
Background:To investigate the associations of lens power with age,axial length(AL),and type 2 diabetes mellitus(DM)inChineseadultsaged5oandabove.Methods:Random clustering sampling was used to identify adults aged 50 y...Background:To investigate the associations of lens power with age,axial length(AL),and type 2 diabetes mellitus(DM)inChineseadultsaged5oandabove.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett's formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with type 2 DM presented higher lens power(0.43 diopter(D),P<0.001)and thicker lens thickness(0.06 mm,P<0.001).In multivariate regression models,there was a positive correlation between lens power and type 2 DM when age<75 years(P<0.001)or AL<25 mm(P<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(P=0.122)or with AL≥25 mm(P=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm.展开更多
Background:To investigate the associations of lens power with age,axial length(AL),and Type 2 diabetes mellitus(DM)in Chinese adults aged 50 and above.Methods:Random clustering sampling was used to identify adults age...Background:To investigate the associations of lens power with age,axial length(AL),and Type 2 diabetes mellitus(DM)in Chinese adults aged 50 and above.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett’s formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with Type 2 DM presented higher lens power(0.43 diopter(D),p<0.001)and thicker lens thickness(0.06 mm,p<0.001).In multivariate regression models,there was a positive correlation between lens power and Type 2 DM when age<75 years(p<0.001)or AL<25 mm(p<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(p=0.122)or with AL≥25 mm(p=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm.展开更多
基金Supported by the Program of Shanghai Academic/Technology Research Leader(No.21XD1402700)the Clinical Research Plan of Shenkang Hospital Development Center of Shanghai(No.SHDC2022CRD001).
文摘AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.
基金supported by the National Natural Science Foundation of China,No. 82171062 (to JFZ)。
文摘Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.
基金Supported by the National Key Research and Development Program of China(No.2016YFC0904800)National Natural Science Foundation of China(No.82101181)+1 种基金China Scholarship Council(No.201506230096)Shanghai Sailing Program(No.19YF1439700).
文摘●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
基金Supported by National Natural Science Foundation of China(No.81570851)Project of Shanghai Medical Key Specialty Construction(No.ZK2019B27)+3 种基金National Project of Shanghai Municipal Commission of Health and Family Planning(No.201740001)Project of Shanghai Jingan District Municipal Commission of Health and Family Planning(No.2018MS12)Advanced and Appropriate Technology Promotion Project of Shanghai Health Commission(No.2019SY012)Shanghai Jiao Tong University Translation Medicine Cross Research Fund Project(No.YG2019QNA61)。
文摘AIM:To analyze differences in ultra-widefield fluorescein angiography(UWFA)findings between dynamic and static images of eyes with diabetic retinopathy(DR).METHODS:This cross-sectional study included 28 eyes of 28 patients with DR undergoing UWFA.A series of UWFA images acquired from each patient were converted into a time-lapse video and used as a dynamic image.A single,clear,arteriovenous phase image was chosen as a static image.Non-perfusion index(NPI)and its correlation with vascular abnormalities in different zones were compared between dynamic and static UWFA imaging.RESULTS:NPI appeared to increase from the center to the far-periphery in both groups.Dynamic NPI was lower in the total retinal area(0.26 vs 0.29,P=0.009)and farperiphery(0.33 vs 0.36,adjusted P=0.042),which was contrary to the static NPI.Far-peripheral NPI was associated with intraretinal microvascular abnormality in the posterior area in both groups.CONCLUSION:Time-lapse dynamic UWFA imaging is a useful modality to differentially diagnose hypofluorescence in the most peripheral region.This modality could provide a reliable method for NPI measurement.
基金funded by National Natural Science Foundation of China(81900869,81730026,81802482)National Key R&D Program(2019YFC0840607,2017YFA0105301)+3 种基金Science and Technology Commission of Shanghai Municipality(17411953000,19495800700)Shanghai Sailing Program(19YF1439500)Talent Project of Revitalizing Liaoning(XLYC1807184)Dalian Science&Technology Innovation Fund(2020JJ26SN050)。
文摘In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.
基金Supported by National Natural Science Foundation of China(No.81570852)。
文摘AIM:To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy(DR).METHODS:Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin.The retinas were harvested at 1 to 24 wk after diabetes onset.Hypoxia-treated mouse microglial cell line(BV2 cells)was employed as the in vitro model to mimic diabetic condition.The expressions of Iba-1,CD11 b,ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction,Western blot and immunofluorescence both in vivo and in vitro.RESULTS:Compared with age-matched normal control,the number of microglia(Iba-1 positive immunostaining)in diabetic rat retinas was increased from 1 to 24 wk of diabetes,which was most obvious at 12 wk of diabetes.Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control;however,there was statistically significant between two groups only at 2 wk after diabetes onset.The m RNA expression of Iba-1 was decreased significantly at 2 and 4 wk of diabetic rat retinas,and remained unchanged at 8 and 12 wk of diabetes.In BV2 cells,there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups;however,its m RNA level was decreased significantly under hypoxia.To further characterize microglial activation,F4/80,CD11 b and inflammatory factors were detected both in vivo and in vitro.Compared with normal control,the expressions of F4/80 and CD11 b as well as the inflammatory factors,such as ICAM-1,i NOS,COX2,IL-1βand IL-6,were increased significantly both in vivo and in vitro.CONCLUSION:Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR.However,Iba-1 immunostaining,in combination with other markers like CD11 b and ICAM-1,could be well reflect the activation of microglia.Thus,it is of great importance to explore other potential marker to evaluate the activation of microglia.
文摘AIM:To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane(ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis(MF).METHODS:A 23-gauge 3-port pars plana vitrectomy was performed on 16 patients with high MF.A parallel arc line along the vascular arcades was scraped out with a curved membrane scraper DSP.Next,an ILM forceps was used to catch hold of the incisal edge of the ILM flap,and the action of releasing and separating was subsequently taken toward the direction of the macular fovea.Next,the ILM forceps was used to grasp the released area,and the whole area coherent ILM peeling covering the macular fovea was implemented thereafter.Finally,the ILM was folded backwards and peeled off in the arc direction.RESULTS:At the final visit,the average central macular thickness decreased remarkably from 423.76±177.67 to 178.24±66.21 μm.The mean logarithm of the minimum angle of resolution best-corrected visual acuity of 1.37±0.59 was significantly alleviated to 0.74±0.59.CONCLUSION:The wide range of whole piece consecutive ILM peeling without preservation of the epifovea is proven to be effective and significantly reduced the occurrence of retinal tear and macular hole.
基金supported by the National Natural Science Foundation of China,No.82171062(to JFZ)Aier Eye Hospital Group Scientific Research Fund,No.AF2101D8(to LMG).
文摘Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.
基金Supported by the Natural Science Foundation of Shanghai(No.18ZR1435700)Clinical Research Project of Shanghai Health and Family Planning Committee(No.201840199)。
文摘AIM:To explore the photopic pupil size behavior in myopic children undergoing overnight orthokeratology(ortho-k)over 1-year period and its effects on the axial elongation.METHODS:A total of 202 Chinese myopic children were enrolled in this prospective clinical trial.Ninetyfive subjects in ortho-k group and eighty-eight subjects in spectacle group completed the 1-year study.Axial length(AL)was measured before enrollment and every 6mo after the start of ortho-k.The photopic pupil diameter(PPD)was determined using the Pentacam AXL and measured in an examination room with lighting of 300-310 Lx.Stepwise multiple linear regression analysis was used to identify variables contribution to axial elongation.RESULTS:Compared with spectacle group,the average 1-year axial elongation was significantly slower in the ortho-k group(0.25±0.27 vs 0.44±0.23 mm,P<0.0001).In ortho-k group,PPDs significantly decreased from 4.21±0.62 mm to 3.94±0.53 mm after 1mo of lens wear(P=0.001,Bonferroni correction)and the change lasts for 3-month visit.No significantly change during the other follow-up visits was found(P>0.05,Bonferroni correction).The 4.81 mm PPD may be a possible cutoff point in the ortho-k group.Subjects with PPD below or equal to 4.81 mm tended to have smaller axial elongation compared to subjects with PPD above 4.81 mm after 1-year period(t=-3.09,P=0.003).In ortho-k group,univariate analyses indicated that those with older age,greater degree of myopia,longer AL,smaller baseline PPD(PPDbaseline)experienced a smaller change in AL.In multivariate analyses,older age,greater AL and smaller PPDbaseline were associated with smaller increases in AL.In spectacle group,PPD tended to be stable(P>0.05,Bonferroni correction)and did not affect axial growth.CONCLUSION:PPDs experience significantly decreases at 1-month and 3-month ortho-k treatment.Children with smaller PPD tend to experience slower axial elongation and may benefit more from ortho-k.
基金Supported by the National Natural Science Foundation of China (No.81970811No.81970810+1 种基金No.82171062)Domestic Science and Technology Cooperation Project of Shanghai Municipal Science and Technology Commission (No.21015800700)。
文摘AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: Twenty-eight eyes from twenty-eight treatment-na?ve patients(14 males and 14 females) with RVO-ME were included in this retrospective study.The retinal vein occlusion(RVO) was comprised of both central retinal vein occlusion(CRVO,n=14) and branch retinal vein occlusion(BRVO,n=14).Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months,in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept.All eyes were imaged with optical coherence tomography angiography(OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection.The visual acuity(VA),central macular thickness(CMT),the number of hyperreflective foci(HRF) recognized as an inflammatory sign in OCT images,and non-perfusion area(NPA),were compared before and after anti-VEGF treatments.RESULTS: The mean interval between baseline and follow-up was 29.4±0.79(range,27-48)d.Compared with the baseline,the VA improved(log MAR 1.5±0.1 vs 0.8±0.1,P<0.05) and CMT decreased(460±34.0 μm vs 268.8±12.0 μm,P<0.05),significantly,after antiVEGF treatment.The number of HRF was decreased significantly(76.5±4.8 vs 47.8±4.3,P<0.05) after antiVEGF treatment.CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME.The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.
基金Supported by the National Natural Science Foundation of China (No.82101132,No.81800878)。
文摘AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and strategies.METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS.RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not(P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls(P>0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.
基金Supported by the National Natural Science Foundation of China(No.81970845)European Union’s Horizon 2020 research and innovation programme under grant agreement(No.778089)。
文摘AIM: To explore the performance in diabetic retinopathy(DR) screening of artificial intelligence(AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera(Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR.RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range(1.47, 1.48, and 1.40) than conventional tabletop cameras(1.30, 1.28, and 1.18;P<0.001). Detection of retinal hemorrhage, hard exudation,and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1%(95%CI: 72.1%-92.2%) and 97.4%(95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory;however, Phoebus showed a high sensitivity(88.2%, 95%CI: 79.4%-97.1%) and low specificity(40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR.CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.
基金Supported by the National Natural Science Foundation of China(No.81730026No.81970816)+2 种基金the National Key R&D Program(No.2017YFA0105301)Science and Technology Commission of Shanghai Municipality(No.20Z11900400No.19495800700)。
文摘AIM:To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial(hES-RPE)cells in vitro,and compare the behaviors and functions of h ESRPE cells on two culture substrates,laminin521(LN-521)and truncated recombinant human vitronectin(VTN-N).METHODS:hES-RPE cells were used in the experiment.The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system.Quantitative real-time polymerase chain reaction was used to evaluate RPE-specific gene expression levels midway(day 10)and at the end(day 20)of the time course.Cell polarity was observed by immunofluorescent staining for apical and basal markers of the RPE.The phagocytic ability of hES-RPE cells was identified by flow cytometry and immunofluorescence.RESULTS:The cell adhesion assay showed that the ability of LN-521 to adhere to hES-RPE cells was dosedependent.With increasing coating concentration,an increasing number of cells attached to the surface of LN-521-coated wells.In contrast,VTN-N presented a strong adhesive ability even at a low concentration.The optimal concentration of LN-521 and VTN-N required to coat and adhesion to hES-RPE cells were 2 and 0.25μg/cm^(2),respectively.Furthermore,both LN-521 and VTN-N could facilitate adoption of the desired cobblestone cellular morphology with tight junction and showed polarity by the hES-RPE cells.However,hES-RPE cells cultivated in VTN-N had a greater phagocytic ability,and it took less time for these hES-RPE cells to mature.CONCLUSION:VTN-N is a more suitable coating substrate for cultivating hES-RPE cells.
基金Supported by the National Natural Science Foundation of China (No.81170874No.81900868)。
文摘AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroidassociated ophthalmopathy(TAO) could be an early sign to detect dysthyroid optic neuropathy(DON). METHODS: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography(OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries(RPC), retinal nerve fiber layer(RNFL), and macular ganglion cell complex(GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. RESULTS: Whole choroidal RPC was significantly reduced in DON(48.24%±0.4978%) compared to normal(50.33%±0.3173%) and TAO without DON(49.16%±0.5463%;P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field(VF) defect in DON(r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed.CONCLUSION: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.
基金Supported by the National Natural Science Foundation of China (No.81900911)the National Key R&D Program of China (No.2016YFC0904800,No.2019YFC0840607)+1 种基金the National Science and Technology Major Project of China (No.2017ZX09304010)the Interdisciplinary Program of Shanghai Jiao Tong University (No.YG2019QN66)。
文摘AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus(ICP and DCP) in patients with retinal deep vascular complex ischemia(RDVCI), using 3D projection artifacts removal(3D PAR) optical coherence tomography angiography(OCTA).METHODS: RDVCI patients and gender-and agematched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density(PFVD) of retinal deep vascular complex(DVC), ICP, and DCP were analyzed, and the percentage of reduction(PR) of PFVD was calculated.RESULTS: Twenty-four eyes in 22 RDVCI patients(20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls(DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%;chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%;chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%;chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%;all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase(P=0.812), but significant difference in chronic phase(P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC(P=0.735) or ICP(P=0.681) was found, but significant difference in the DCP(P=0.041).CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.
基金This work was supported by grants from the Chinese National Natural Science Foundation(No.82071012)The Project of Shanghai Shen Kang Hospital Development Centre(Nos.SHDC2020CR30538 and SHDC2018110)+3 种基金Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases,Shanghai,China(No.19DZ2250100)The Science and Technology Commission of Shanghai Municipality(No.20DZ1100200)Shanghai Public Health System Three-Year Plan-Key Subjects(No.GWV10.1-XK7)Shanghai General Hospital,Clinical Research(CTCCR-2018Z01)。
文摘Diabetic retinopathy(DR)is an important cause of blindness globally,and its prevalence is increasing.Early detection and intervention can help change the outcomes of the disease.The rapid development of artificial intelligence(AI)in recent years has led to new possibilities for the screening and diagnosis of DR.An AI-based diagnostic system for the detection of DR has significant advantages,such as high efficiency,high accuracy,and lower demand for human resources.At the same time,there are shortcomings,such as the lack of standards for development and evaluation and the limited scope of application.This article demonstrates the current applications of AI in the field of DR,existing problems,and possible future development directions.
基金supported by grants from the National Natural Science Foundation of China(81730026)National Key Technologies R&D Program(2017YFA0105301)Shanghai Hospital Development Center(SHDC2020CR2040B and SHDC2020CR5014).
文摘Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithelial-mesenchymal transition(EMT)contribute to the fibrosis formation.N^(6)-Methyladenosine(m^(6)A)modification has been implicated in the EMT process and multiple fibrotic diseases.The role of m^(6)A modification in EMT-related subretinal fibrosis has not yet been elucidated.In this study,we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization,METTL3 was upregulated in RPE cells.Through m^(6)A epitranscriptomic microarray and further verification,high-mobility group AT-hook 2(HMGA2)was identified as thekey downstream target of METTL3,subsequently activating potent EMT-inducing transcription factor SNAIL.Finally,by subretinal injections of adeno-associated virus vectors,we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo.In conclusion,our present research identified an epigenetic mechanism of METTL3-m^(6)A-HMGA2 in subretinal fibrosis and EMT of RPE cells,providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.
基金supported by grants from the National Natural Science Foundation of China(81570852,81970810,81970811)National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirtieth Five-year Plan Period(2019ZX09301113).
文摘Background:Although vascular endothelial growth factor A(VEGF-A)is known to play a key role in causing retinal edema,whether and how VEGF-A induces intracellular edema in the retina still remains unclear.Methods:Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin.Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset.rMC-1 cells(rat Müller cell line)were treated with glyoxal for 24 h with or without ranibizumab.The expression levels of inwardly rectifying K^(+)channel 4.1(Kir4.1),aquaporin 4(AQP4),Dystrophin 71(Dp71),VEGF-A,glutamine synthetase(GS)and sodium-potassium-ATPase(Na^(+)-K^(+)-ATPase)were examined using Western blot.VEGF-A in the supernatant of the cell culture was detected with ELISA.The intracellular potassium and sodium levels were detected with specific indicators.Results:Compared with normal control,protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas,which were prevented by ranibizumab.The above changes were recapitulated in vitro.Similarly,the intracellular potassium level in glyoxal-treated rMC-1 cells was increased,while the intracellular sodium level and Na^(+)-K^(+)-ATPase protein level remained unchanged,compared with control.However,ranibizumab treatment decreased intracellular sodium,but not potassium.Conclusion:Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A.It also caused a reduction in intracellular osmotic pressure.
基金This study was funded by the National Natural Science Foundation of China(Grant Nos.81670898 and 81703287)the Shanghai Three-Year Public Health Action Program(Project.Nos.GWIV-3.3 and GWIV-13.1)+6 种基金the Shanghai High-level Overseas Training Team Programon Eye Public Health(Project No.GWTD2015S08)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(Project No.20172022)the Shanghai General Hospital,Clinical Research(Project No.CTCCR-2018Z01)the Shanghai Science and Technology Commission Research Project(Project No.17ZR1426900)the Shanghai Municipal Planning Commission of Science and Research Fund(Project No.201640090)the National Key R&D Program of China(Project Nos.2016YFC0904800,2019YFC0840607)the National Science and Technology Major Project of China(Project No.2017ZX09304010).
文摘Background:To investigate the associations of lens power with age,axial length(AL),and type 2 diabetes mellitus(DM)inChineseadultsaged5oandabove.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett's formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with type 2 DM presented higher lens power(0.43 diopter(D),P<0.001)and thicker lens thickness(0.06 mm,P<0.001).In multivariate regression models,there was a positive correlation between lens power and type 2 DM when age<75 years(P<0.001)or AL<25 mm(P<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(P=0.122)or with AL≥25 mm(P=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm.
基金This study was funded by the National Natural Science Foundation of China(Grant No.:81670898 and 81703287,Beijing,China)the Shanghai Three-Year Public Health Action Program(Project Nos.GWIV-3.3 and GWIV-13.1,Shanghai,China)+7 种基金the Shanghai High-level Overseas Training Team Program on Eye Public Health(Project No.GWTD2015S08,Shanghai,China)Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(Project No.20172022,Shanghai,China)Shanghai General Hospital,Clinical Research(Project No.CTCCR-2018Z01,Shanghai,China)the Shanghai Science and Technology Commission Research Project(Project No.17ZR1426900,Shanghai,China)the Shanghai Municipal Planning Commission of Science and Research Fund(Project No.201640090,Shanghai,China)National Key R&D Program of China(Project No.2016YFC0904800,2019YFC0840607)National Science and Technology Major Project of China(Project No.2017ZX09304010)The sponsors or funding organizations had no role in the design or conduct of this research.
文摘Background:To investigate the associations of lens power with age,axial length(AL),and Type 2 diabetes mellitus(DM)in Chinese adults aged 50 and above.Methods:Random clustering sampling was used to identify adults aged 50 years and above in urban regions of Shanghai.The participants underwent a comprehensive ophthalmic examination including subjective refraction,autorefraction,and IOL-Master.The crystalline lens power was calculated using Bennett’s formula.Results:A total of 4177 adults were included.A linear decrease in lens power was observed both with age and with AL,followed by a stop of lens power loss after the age of 70 or when AL≥25 mm,respectively.Participants with Type 2 DM presented higher lens power(0.43 diopter(D),p<0.001)and thicker lens thickness(0.06 mm,p<0.001).In multivariate regression models,there was a positive correlation between lens power and Type 2 DM when age<75 years(p<0.001)or AL<25 mm(p<0.001)after adjusting for other factors,while no significant association was found in participants aged≥75 years(p=0.122)or with AL≥25 mm(p=0.172).Conclusions:The lens power in adults aged 50 and above exhibited two stages with age and with AL.Type 2 DM caused an increase in lens power,which was not seen in participants aged≥75 years or with AL≥25 mm.
