Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these me...To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.展开更多
Recently published in Joule,Feng Liu and colleagues from Shanghai Jiaotong University reported a record-breaking 20.8%power conversion efficiency in organic solar cells(OSCs)with an interpenetrating fibril network act...Recently published in Joule,Feng Liu and colleagues from Shanghai Jiaotong University reported a record-breaking 20.8%power conversion efficiency in organic solar cells(OSCs)with an interpenetrating fibril network active layer morphology,featuring a bulk p-in structure and proper vertical segregation achieved through additive-assisted layer-by-layer deposition.This optimized hierarchical gradient fibrillar morphology and optical management synergistically facilitates exciton diffusion,reduces recombination losses,and enhances light capture capability.This approach not only offers a solution to achieving high-efficiency devices but also demonstrates the potential for commercial applications of OSCs.展开更多
BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic im...BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.展开更多
BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of va...BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.展开更多
AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-fou...AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-four rats were categorized into four groups of six rats:healthy(HG),5-FU(FUG),ATP+5-FU(AFU),and melatonin+5-FU(MFU).ATP(4 mg/kg)and melatonin(10 mg/kg)were administered intraperitoneally and orally,respectively.One hour after ATP and melatonin administration,rats in the AFU,MFU,and FUG were intraperitoneally injected with 5-FU(100 mg/kg).ATP and melatonin were administered once daily for 10d.5-FU was administered at a single dose on days 1,3,and 5 of the experiment.After 10d,the rats were euthanized and optic nerve tissues were extracted.Optic nerve tissues were biochemically and histopathologically examined.RESULTS:ATP and melatonin treatments inhibited the increase in malondialdehyde(MDA)and interleukin-6(IL-6)levels,which were elevated in the FUG.The treatments also prevented the decrease in total glutathione(tGSH)levels and the superoxide dismutase(SOD)and catalase(CAT)activities(P<0.001).This inhibition was higher in the ATP group than in the melatonin group(P<0.001).ATP prevented histopathological damage better than melatonin(P<0.05).CONCLUSION:ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage.In addition,ATP treatment shows better protective effects than melatonin.展开更多
Kinesin is an archetypal microtubule-based molecular motor that can generate force to transport cargo in cells. The load dependence of the detachment rate is an important factor of the kinesin motor, the determination...Kinesin is an archetypal microtubule-based molecular motor that can generate force to transport cargo in cells. The load dependence of the detachment rate is an important factor of the kinesin motor, the determination of which is critically related to the chemomechanical coupling mechanism of the motor. Here, we use three models for the load dependence of the detachment rate of the kinesin motor to study theoretically and numerically the maximal force generated and microtubuleattachment duration of the motor. By comparing the theoretical and numerical results with the available experimental data,we show that only one model can explain well the available experimental data, indicating that only this model can be applicable to the kinesin motor.展开更多
AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2....AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2.1y(range:4-10y),underwent comprehensive ophthalmic and refractive evaluations.Spectral domain-optical coherence tomography(SD-OCT)and multifocal electroretinography(mfERG)were conducted to analyze the macular retinal thickness and the first-order response P1 ring of the mfERG in the amblyopic eye(AE)compared to the fellow good eye(GE).RESULTS:Initially,visual acuity in the AE ranged from 20/800 to 20/40,while the GE exhibited a range of 20/25 to 20/20(P<0.01).After 6mo of treatment,17 patients demonstrated improved visual acuity in the AE to 20/50 or better,while 4 children showed no improvement.SD-OCT revealed comparable macular and optic disc structures between the AE and GE.Prior to treatment,the mfERG P1 ring amplitude was significantly reduced in the AE compared to GE(P<0.05).The AE/GE ratio of P1 ring amplitude showed significant improvement post-treatment.However,a smaller AE/GE ratio before treatment was associated with poorer improvement post-treatment.CONCLUSION:In the management of functional amblyopia,a thorough assessment of amblyopic eye examinations is crucial.Approximately 20%of amblyopic eyes may not achieve significant improvement in visual acuity,despite the absence of detectable organic retinal abnormalities.mfERG may reveal underlying abnormalities.Integrating mfERG into initial assessments or treatment follow-ups can aid in identifying potential hidden retinal defects and predicting the prognosis of the amblyopic eye.展开更多
With the advancement of artificial intelligence,optic in-sensing reservoir computing based on emerging semiconductor devices is high desirable for real-time analog signal processing.Here,we disclose a flexible optomem...With the advancement of artificial intelligence,optic in-sensing reservoir computing based on emerging semiconductor devices is high desirable for real-time analog signal processing.Here,we disclose a flexible optomemristor based on C_(27)H_(30)O_(15)/FeOx heterostructure that presents a highly sensitive to the light stimuli and artificial optic synaptic features such as short-and long-term plasticity(STP and LTP),enabling the developed optomemristor to implement complex analogy signal processing through building a real-physical dynamic-based in-sensing reservoir computing algorithm and yielding an accuracy of 94.88%for speech recognition.The charge trapping and detrapping mediated by the optic active layer of C_(27)H_(30)O_(15) that is extracted from the lotus flower is response for the positive photoconductance memory in the prepared optomemristor.This work provides a feasible organic−inorganic heterostructure as well as an optic in-sensing vision computing for an advanced optic computing system in future complex signal processing.展开更多
AIM:To examine the subclinical alterations in the retina and choroid between patients with 2019 coronavirus disease(COVID-19)-related lung involvement and the healthy control group.METHODS:In this prospective case-con...AIM:To examine the subclinical alterations in the retina and choroid between patients with 2019 coronavirus disease(COVID-19)-related lung involvement and the healthy control group.METHODS:In this prospective case-control study,85 cases with lung involvement due to COVID-19 and 50 healthy cases were included.Best-corrected visual acuity,intraocular pressure measurement,and anterior and posterior segment examination were performed on both eyes for each individual.Choroidal and retinal changes were examined and recorded by optical coherence tomography angiography.RESULTS:All choroidal thickness measurements of the COVID-19 group showed no statistically significant difference when compared to healthy individuals.When vascular density and perfusion density values were compared,there was a decrease in the average of these values in the COVID-19 group,although it was not statistically significant(P=0.088,P=0.065 respectively).When the fovea avascular zone(FAZ)area values were compared,the average was 0.57±0.38 in the COVID-19 group,while it was 0.54±0.24 in the control group.CONCLUSION:Although our data are not statistically significant,the decrease in vascularity and perfusion and the accompanying FAZ expansion are detected in the acute period(1st month).These changes may anatomically alter the retina in the long term and affect functional vision.Future ischemia-related alterations in the retina caused by a prior COVID-19 infection may arise in situations without comorbidities and may require concern in the patient’s systemic assessment.展开更多
Weibel instability is a promising candidate mechanism for collisionless shock formation in astrophysical systems.Capturing the underlying physics of Weibel instability will help us to understand the astrophysical shoc...Weibel instability is a promising candidate mechanism for collisionless shock formation in astrophysical systems.Capturing the underlying physics of Weibel instability will help us to understand the astrophysical shock formation,magnetic field generation and amplification,particle acceleration,and so on.Laboratory astrophysics,provides a new way to study these microphysics in controlled conditions.At Shenguang-Ⅱlaser facility,the interpenetrating plasma flows are generated by eight laser beams irradiating a pair of opposing foils to mimic the supernova explosion and the ejecta sweeping up the surrounding medium.Evolution of collisionless interpenetrating plasma flows is observed using optical diagnostics.Filamentary structures appear in the interaction region and the associated magnetic strength is measured about 40 T.Theoretical analysis and simulations indicate that these characteristics are induced by nonlinear Weibel instability.展开更多
In the past few decades,ion engines have been widely used in deep-space propulsion and satellite station-keeping.The aim of extending the thruster lifetime is still one of the most important parts during the design st...In the past few decades,ion engines have been widely used in deep-space propulsion and satellite station-keeping.The aim of extending the thruster lifetime is still one of the most important parts during the design stage of ion engine.As one of the core components of ion engine,the grid assembly of ion optic systems may experience long-term ion sputtering in extreme electro-thermal environments,which will eventually lead to its structural and electron-backstreaming failures.In this paper,the current studies of the grid assembly erosion process are systematically analyzed from the aspects of sputtering damage process of grid materials,numerical simulations,and measurements of erosion characteristics of grid assembly.The advantages and disadvantages of various erosion prediction models are highlighted,and the key factors and processes affecting the prediction accuracy of grid assembly erosion patterns are analyzed.Three different types of experimental methods of grid assembly erosion patterns are compared.The analysis in this paper is of great importance for selecting the sputter-resistant grid materials,as well as establishing the erosion models and measurement methods to accurately determine the erosion rate and failure modes of grid assembly.Consequently,the working conditions and structure parameters of ion optic systems could be optimized based on erosion models to promote the ion engine lifetime.展开更多
AIM:To compare the macular and optic nerve perfusion and vascular architecture using optical coherence tomography angiography(OCTA)in normal eyes of Egyptian(Caucasians)and South Asian(Asians)volunteers.METHODS:Cross-...AIM:To compare the macular and optic nerve perfusion and vascular architecture using optical coherence tomography angiography(OCTA)in normal eyes of Egyptian(Caucasians)and South Asian(Asians)volunteers.METHODS:Cross-sectional analytical OCTA study performed on 90 eyes of South Asian(n=45)and Egyptians(n=45)were analyzed.All participants underwent bestcorrected visual acuity test,slit lamp,and fundus examination.OCTA images;macular 6×6 mm^(2) grid and optic nerve 4.5×4.5 mm^(2) grid were used to examine the parafoveal and peripapillary regions,respectively.RESULTS:The mean capillary vessel density(CVD)in macular sectors among South Asians and Egyptians participants were(50.31%±2.53%,51.2%±5.93%)and(49.71%±3.6%,51.94%±4.79%)in superficial(SCP)and deep capillary plexuses(DCP),respectively(P>0.05).Mean CVD in both groups was higher in DCP compared to SCP in all sectors but was not significant(P>0.05).Mean foveal CVD increases with an increase in central retinal thickness in both SCP and DCP(P<0.001),among both groups.Mean area of the foveal avascular zone(FAZ)was 0.28±0.09 and 0.27±0.08 mm2 in South Asian and Egyptians,respectively.FAZ area decreases with an increase in the thickness and foveal CVD(P<0.001).Mean CVD in the peripapillary area was 48.23%±5.78% in South Asian and 49.52%±2.38% in Egyptian volunteers.The mean retinal nerve fiber layer thickness was found to be higher in the nasal quadrant among South Asian females than the Egyptian females(P<0.05).CONCLUSION:No significant racial disparity is found in this study.The findings are helpful for assessing and improving the normative data on the differences in South Asian and Egyptian populations.展开更多
AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases a...AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases at Rajavithi Hospital between 2007 and 2016 was conducted to determine time to occurrence of NAION and evaluate associated risk factors.RESULTS:Hypertension and dyslipidemia were the most common pre-existing vascular diseases and there was a significant male predominance in the NAION group.The mean age of the NAION group was significantly higher than that of the group without NAION.A higher proportion of subjects in the NAION group had hypertension,dyslipidemia,high diastolic blood pressure,smokers,and had a small cup-to-disc ratio(CDR).Higher levels of triglycerides and lowdensity lipoprotein-cholesterol in the group with NAION.Fiftyfive patients among 266 participants(20.68%)developed NAION during a mean follow-up time of 81.26±25.04mo.In a multivariable logistic regression analysis,dyslipidemia(OR=8.36,95%CI,3.447–20.273,P<0.001),high low density lipoprotein levels(OR=1.017,95%CI,1.004–1.029,P=0.009),and small CDR(OR=11.92,95%CI,4.477–31.741,P<0.001)were significant risk factors for NAION development.Smoking was the strongest predictive risk(OR=12.843,95%CI,3.959–41.659,P<0.001).Vascular complications of T2DM and aspirin were not associated with NAION.CONCLUSION:T2DM patients with dyslipidemia or a small CDR should be carefully followed up as they are at increased risk of developing NAION.展开更多
AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This...AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.展开更多
Semiconductor moirésuperlattices provide great platforms for exploring exotic collective excitations.Optical Stark effect,a shift of the electronic transition in the presence of a light field,provides an ultrafas...Semiconductor moirésuperlattices provide great platforms for exploring exotic collective excitations.Optical Stark effect,a shift of the electronic transition in the presence of a light field,provides an ultrafast and coherent method of manipulating matter states,which,however,has not been demonstrated in moirématerials.Here,we report the valleyselective optical Stark effect of moiréexcitons in the WSe_(2)/WS_(2)superlattice by using transient reflection spectroscopy.Prominent valley-selective energy shifts up to 7.8 meV have been observed for moiréexcitons,corresponding to pseudomagnetic fields as large as 34 T.Our results provide a route to coherently manipulate exotic states in moirésuperlattices.展开更多
Underground mine pillars provide natural stability to the mine area,allowing safe operations for workers and machinery.Extensive prior research has been conducted to understand pillar failure mechanics and design safe...Underground mine pillars provide natural stability to the mine area,allowing safe operations for workers and machinery.Extensive prior research has been conducted to understand pillar failure mechanics and design safe pillar layouts.However,limited studies(mostly based on empirical field observation and small-scale laboratory tests)have considered pillar-support interactions under monotonic loading conditions for the design of pillar-support systems.This study used a series of large-scale laboratory compression tests on porous limestone blocks to analyze rock and support behavior at a sufficiently large scale(specimens with edge length of 0.5 m)for incorporation of actual support elements,with consideration of different w/h ratios.Both unsupported and supported(grouted rebar rockbolt and wire mesh)tests were conducted,and the surface deformations of the specimens were monitored using three-dimensional(3D)digital image correlation(DIC).Rockbolts instrumented with distributed fiber optic strain sensors were used to study rockbolt strain distribution,load mobilization,and localized deformation at different w/h ratios.Both axial and bending strains were observed in the rockbolts,which became more prominent in the post-peak region of the stress-strain curve.展开更多
AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective...AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).展开更多
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.
基金Technology Development Program of Jilin Province(YDZJ202201ZYTS640)the National Key Research and Development Program of China(2022YFB4200400)funded by MOST+4 种基金the National Natural Science Foundation of China(52172048 and 52103221)Shandong Provincial Natural Science Foundation(ZR2021QB024 and ZR2021ZD06)Guangdong Basic and Applied Basic Research Foundation(2023A1515012323,2023A1515010943,and 2024A1515010023)the Qingdao New Energy Shandong Laboratory open Project(QNESL OP 202309)the Fundamental Research Funds of Shandong University.
文摘Recently published in Joule,Feng Liu and colleagues from Shanghai Jiaotong University reported a record-breaking 20.8%power conversion efficiency in organic solar cells(OSCs)with an interpenetrating fibril network active layer morphology,featuring a bulk p-in structure and proper vertical segregation achieved through additive-assisted layer-by-layer deposition.This optimized hierarchical gradient fibrillar morphology and optical management synergistically facilitates exciton diffusion,reduces recombination losses,and enhances light capture capability.This approach not only offers a solution to achieving high-efficiency devices but also demonstrates the potential for commercial applications of OSCs.
文摘BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.
文摘BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.
文摘AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-four rats were categorized into four groups of six rats:healthy(HG),5-FU(FUG),ATP+5-FU(AFU),and melatonin+5-FU(MFU).ATP(4 mg/kg)and melatonin(10 mg/kg)were administered intraperitoneally and orally,respectively.One hour after ATP and melatonin administration,rats in the AFU,MFU,and FUG were intraperitoneally injected with 5-FU(100 mg/kg).ATP and melatonin were administered once daily for 10d.5-FU was administered at a single dose on days 1,3,and 5 of the experiment.After 10d,the rats were euthanized and optic nerve tissues were extracted.Optic nerve tissues were biochemically and histopathologically examined.RESULTS:ATP and melatonin treatments inhibited the increase in malondialdehyde(MDA)and interleukin-6(IL-6)levels,which were elevated in the FUG.The treatments also prevented the decrease in total glutathione(tGSH)levels and the superoxide dismutase(SOD)and catalase(CAT)activities(P<0.001).This inhibition was higher in the ATP group than in the melatonin group(P<0.001).ATP prevented histopathological damage better than melatonin(P<0.05).CONCLUSION:ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage.In addition,ATP treatment shows better protective effects than melatonin.
基金Project supported by Youth Project of Science and Technology Research Program of Chongqing Education Commission of China (Grant No. KJQN202404522)。
文摘Kinesin is an archetypal microtubule-based molecular motor that can generate force to transport cargo in cells. The load dependence of the detachment rate is an important factor of the kinesin motor, the determination of which is critically related to the chemomechanical coupling mechanism of the motor. Here, we use three models for the load dependence of the detachment rate of the kinesin motor to study theoretically and numerically the maximal force generated and microtubuleattachment duration of the motor. By comparing the theoretical and numerical results with the available experimental data,we show that only one model can explain well the available experimental data, indicating that only this model can be applicable to the kinesin motor.
基金Supported by the National Natural Science Foundation of China(No.82271100)the Jiangsu Science and Technology Support Program(No.BE2022805)the Clinical Skills Enhancement Program of Jiangsu Province Hospital(No.JSPH-MC-2022-24).
文摘AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2.1y(range:4-10y),underwent comprehensive ophthalmic and refractive evaluations.Spectral domain-optical coherence tomography(SD-OCT)and multifocal electroretinography(mfERG)were conducted to analyze the macular retinal thickness and the first-order response P1 ring of the mfERG in the amblyopic eye(AE)compared to the fellow good eye(GE).RESULTS:Initially,visual acuity in the AE ranged from 20/800 to 20/40,while the GE exhibited a range of 20/25 to 20/20(P<0.01).After 6mo of treatment,17 patients demonstrated improved visual acuity in the AE to 20/50 or better,while 4 children showed no improvement.SD-OCT revealed comparable macular and optic disc structures between the AE and GE.Prior to treatment,the mfERG P1 ring amplitude was significantly reduced in the AE compared to GE(P<0.05).The AE/GE ratio of P1 ring amplitude showed significant improvement post-treatment.However,a smaller AE/GE ratio before treatment was associated with poorer improvement post-treatment.CONCLUSION:In the management of functional amblyopia,a thorough assessment of amblyopic eye examinations is crucial.Approximately 20%of amblyopic eyes may not achieve significant improvement in visual acuity,despite the absence of detectable organic retinal abnormalities.mfERG may reveal underlying abnormalities.Integrating mfERG into initial assessments or treatment follow-ups can aid in identifying potential hidden retinal defects and predicting the prognosis of the amblyopic eye.
基金supported by the Key Project of Chongqing Natural Science Foundation Joint Fund[CSTB2023NSCQ-LZX0103,(G.Z.)]Chongqing Natural Science Foundation[CSTB2024NSCQ-MSX0012,(C.L.)]+1 种基金Fundamental Research Funds for the Central Universities[SWUZLPY03,(G.Z.)]Fundamental Research Funds for the Central Universities[Swu020019,(G.Z.):SWU-XDJH202319,(G.Z.)1].
文摘With the advancement of artificial intelligence,optic in-sensing reservoir computing based on emerging semiconductor devices is high desirable for real-time analog signal processing.Here,we disclose a flexible optomemristor based on C_(27)H_(30)O_(15)/FeOx heterostructure that presents a highly sensitive to the light stimuli and artificial optic synaptic features such as short-and long-term plasticity(STP and LTP),enabling the developed optomemristor to implement complex analogy signal processing through building a real-physical dynamic-based in-sensing reservoir computing algorithm and yielding an accuracy of 94.88%for speech recognition.The charge trapping and detrapping mediated by the optic active layer of C_(27)H_(30)O_(15) that is extracted from the lotus flower is response for the positive photoconductance memory in the prepared optomemristor.This work provides a feasible organic−inorganic heterostructure as well as an optic in-sensing vision computing for an advanced optic computing system in future complex signal processing.
文摘AIM:To examine the subclinical alterations in the retina and choroid between patients with 2019 coronavirus disease(COVID-19)-related lung involvement and the healthy control group.METHODS:In this prospective case-control study,85 cases with lung involvement due to COVID-19 and 50 healthy cases were included.Best-corrected visual acuity,intraocular pressure measurement,and anterior and posterior segment examination were performed on both eyes for each individual.Choroidal and retinal changes were examined and recorded by optical coherence tomography angiography.RESULTS:All choroidal thickness measurements of the COVID-19 group showed no statistically significant difference when compared to healthy individuals.When vascular density and perfusion density values were compared,there was a decrease in the average of these values in the COVID-19 group,although it was not statistically significant(P=0.088,P=0.065 respectively).When the fovea avascular zone(FAZ)area values were compared,the average was 0.57±0.38 in the COVID-19 group,while it was 0.54±0.24 in the control group.CONCLUSION:Although our data are not statistically significant,the decrease in vascularity and perfusion and the accompanying FAZ expansion are detected in the acute period(1st month).These changes may anatomically alter the retina in the long term and affect functional vision.Future ischemia-related alterations in the retina caused by a prior COVID-19 infection may arise in situations without comorbidities and may require concern in the patient’s systemic assessment.
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2022YFA1603200 and 2022YFA1603204)the Fund from the Chinese Academy of Sciences Youth Interdisciplinary Team(Grant No.JCTD2022-05)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences,the National Natural Science Foundation of China(Grant Nos.11873061 and 12473099)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDA25030500,XDA25010100,and XDA25030200)。
文摘Weibel instability is a promising candidate mechanism for collisionless shock formation in astrophysical systems.Capturing the underlying physics of Weibel instability will help us to understand the astrophysical shock formation,magnetic field generation and amplification,particle acceleration,and so on.Laboratory astrophysics,provides a new way to study these microphysics in controlled conditions.At Shenguang-Ⅱlaser facility,the interpenetrating plasma flows are generated by eight laser beams irradiating a pair of opposing foils to mimic the supernova explosion and the ejecta sweeping up the surrounding medium.Evolution of collisionless interpenetrating plasma flows is observed using optical diagnostics.Filamentary structures appear in the interaction region and the associated magnetic strength is measured about 40 T.Theoretical analysis and simulations indicate that these characteristics are induced by nonlinear Weibel instability.
基金co-supported by the National Key R&D Program of China(No.2022YFB3403500)the National Natural Science Foundation of China(No.NSFC52202460)the China Postdoctoral Science Foundation(Nos.2021M690392,2021TQ0036,and 2023TQ0031)。
文摘In the past few decades,ion engines have been widely used in deep-space propulsion and satellite station-keeping.The aim of extending the thruster lifetime is still one of the most important parts during the design stage of ion engine.As one of the core components of ion engine,the grid assembly of ion optic systems may experience long-term ion sputtering in extreme electro-thermal environments,which will eventually lead to its structural and electron-backstreaming failures.In this paper,the current studies of the grid assembly erosion process are systematically analyzed from the aspects of sputtering damage process of grid materials,numerical simulations,and measurements of erosion characteristics of grid assembly.The advantages and disadvantages of various erosion prediction models are highlighted,and the key factors and processes affecting the prediction accuracy of grid assembly erosion patterns are analyzed.Three different types of experimental methods of grid assembly erosion patterns are compared.The analysis in this paper is of great importance for selecting the sputter-resistant grid materials,as well as establishing the erosion models and measurement methods to accurately determine the erosion rate and failure modes of grid assembly.Consequently,the working conditions and structure parameters of ion optic systems could be optimized based on erosion models to promote the ion engine lifetime.
文摘AIM:To compare the macular and optic nerve perfusion and vascular architecture using optical coherence tomography angiography(OCTA)in normal eyes of Egyptian(Caucasians)and South Asian(Asians)volunteers.METHODS:Cross-sectional analytical OCTA study performed on 90 eyes of South Asian(n=45)and Egyptians(n=45)were analyzed.All participants underwent bestcorrected visual acuity test,slit lamp,and fundus examination.OCTA images;macular 6×6 mm^(2) grid and optic nerve 4.5×4.5 mm^(2) grid were used to examine the parafoveal and peripapillary regions,respectively.RESULTS:The mean capillary vessel density(CVD)in macular sectors among South Asians and Egyptians participants were(50.31%±2.53%,51.2%±5.93%)and(49.71%±3.6%,51.94%±4.79%)in superficial(SCP)and deep capillary plexuses(DCP),respectively(P>0.05).Mean CVD in both groups was higher in DCP compared to SCP in all sectors but was not significant(P>0.05).Mean foveal CVD increases with an increase in central retinal thickness in both SCP and DCP(P<0.001),among both groups.Mean area of the foveal avascular zone(FAZ)was 0.28±0.09 and 0.27±0.08 mm2 in South Asian and Egyptians,respectively.FAZ area decreases with an increase in the thickness and foveal CVD(P<0.001).Mean CVD in the peripapillary area was 48.23%±5.78% in South Asian and 49.52%±2.38% in Egyptian volunteers.The mean retinal nerve fiber layer thickness was found to be higher in the nasal quadrant among South Asian females than the Egyptian females(P<0.05).CONCLUSION:No significant racial disparity is found in this study.The findings are helpful for assessing and improving the normative data on the differences in South Asian and Egyptian populations.
文摘AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases at Rajavithi Hospital between 2007 and 2016 was conducted to determine time to occurrence of NAION and evaluate associated risk factors.RESULTS:Hypertension and dyslipidemia were the most common pre-existing vascular diseases and there was a significant male predominance in the NAION group.The mean age of the NAION group was significantly higher than that of the group without NAION.A higher proportion of subjects in the NAION group had hypertension,dyslipidemia,high diastolic blood pressure,smokers,and had a small cup-to-disc ratio(CDR).Higher levels of triglycerides and lowdensity lipoprotein-cholesterol in the group with NAION.Fiftyfive patients among 266 participants(20.68%)developed NAION during a mean follow-up time of 81.26±25.04mo.In a multivariable logistic regression analysis,dyslipidemia(OR=8.36,95%CI,3.447–20.273,P<0.001),high low density lipoprotein levels(OR=1.017,95%CI,1.004–1.029,P=0.009),and small CDR(OR=11.92,95%CI,4.477–31.741,P<0.001)were significant risk factors for NAION development.Smoking was the strongest predictive risk(OR=12.843,95%CI,3.959–41.659,P<0.001).Vascular complications of T2DM and aspirin were not associated with NAION.CONCLUSION:T2DM patients with dyslipidemia or a small CDR should be carefully followed up as they are at increased risk of developing NAION.
基金Supported by the Suzhou Medical Innovation Application Research Project(SZM2023027).
文摘AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.
基金Project supported by the National Key R&D Program of China(Grant Nos.2022YFA1402400 and 2022YFA1405400)the National Natural Science Foundation of China(Grant Nos.11934011 and 12274365)+3 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LR24A040001)Open project of Key Laboratory of Artificial Structures and Quantum Control(Ministry of Education)of Shanghai Jiao Tong Universitysupport from the JSPS KAKENHI(Grant Nos.20H00354 and 23H02052)World Premier International Research Center Initiative(WPI),MEXT,Japan。
文摘Semiconductor moirésuperlattices provide great platforms for exploring exotic collective excitations.Optical Stark effect,a shift of the electronic transition in the presence of a light field,provides an ultrafast and coherent method of manipulating matter states,which,however,has not been demonstrated in moirématerials.Here,we report the valleyselective optical Stark effect of moiréexcitons in the WSe_(2)/WS_(2)superlattice by using transient reflection spectroscopy.Prominent valley-selective energy shifts up to 7.8 meV have been observed for moiréexcitons,corresponding to pseudomagnetic fields as large as 34 T.Our results provide a route to coherently manipulate exotic states in moirésuperlattices.
基金the funding support from Alpha Foundation for the Improvement of Mine Safety and Health Inc.(ALPHAFOUNDATION,Grant No.AFC820-52)。
文摘Underground mine pillars provide natural stability to the mine area,allowing safe operations for workers and machinery.Extensive prior research has been conducted to understand pillar failure mechanics and design safe pillar layouts.However,limited studies(mostly based on empirical field observation and small-scale laboratory tests)have considered pillar-support interactions under monotonic loading conditions for the design of pillar-support systems.This study used a series of large-scale laboratory compression tests on porous limestone blocks to analyze rock and support behavior at a sufficiently large scale(specimens with edge length of 0.5 m)for incorporation of actual support elements,with consideration of different w/h ratios.Both unsupported and supported(grouted rebar rockbolt and wire mesh)tests were conducted,and the surface deformations of the specimens were monitored using three-dimensional(3D)digital image correlation(DIC).Rockbolts instrumented with distributed fiber optic strain sensors were used to study rockbolt strain distribution,load mobilization,and localized deformation at different w/h ratios.Both axial and bending strains were observed in the rockbolts,which became more prominent in the post-peak region of the stress-strain curve.
基金Supported by FCT/MCTES UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020)UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020)+1 种基金IDI&CA grant IPL/2022/MetAllAMD_ESTeSL by H&TRC-Health&Technology Research Center,ESTeSL-Escola Superior de Tecnologia da Saúde,Instituto Politécnico de Lisboaby Retina Institute of Lisbon(IRL).
文摘AIM:To quantify and compare longitudinal thickness changes of the ganglion cell complex(GCC)and the choroid in patients with different patterns of age-related macular degeneration(AMD)progression.METHODS:Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye(with no evidence of advanced AMD).A total of 64 participants were included from the Instituto de Retina de Lisboa(IRL)study(IPL/2022/MetAllAMD_ESTeSL)and divided into 4 groups according to the Rotterdam classification for AMD.Spectral domain optical coherence tomography(SD-OCT)was used to assess and quantify GCC and choroid thickness at two time points(first visit vs last visit)with a minimum interval of 3y.RESULTS:In the GCC inner ring,a thinner thickness(P=0.001)was observed in the atrophic AMD group(51.3±21.4μm)compared to the early AMD(84.3±11.5μm),intermediate AMD(77.6±16.1μm)and neovascular AMD(88.9±16.3μm)groups.Choroidal thickness quantification showed a generalized reduction in the central circle(P=0.002)and inner ring(P=0.001).Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD(-13%;P<0.01).CONCLUSION:The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative(GCC)or vascular(choroid)pattern in the intermediate and atrophic AMD.The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages(atrophic or neovascular).