Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellula...Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellular mechanisms,including inflammation,cell migration,and the activation of proliferative signaling pathways.One of the most challenging complications of RRD is proliferative vitreoretinopathy(PVR),which refers to the proliferation and contraction of fibrocellular membranes on the retinal surface and in the vitreous cavity.PVR is a major cause of surgical failure in RRD,as it can lead to recurrent retinal detachment and severe vision loss.However,the pathogenesis of PVR is not yet fully understood,and the treatment options are quite limited.Recent advances in analytical techniques have offered valuable insights into the molecular alterations present in the subretinal fluid(SRF)of patients with RRD.This review seeks to consolidate the current knowledge regarding the SRF profile in RRD and PVR,emphasizing potential biomarkers and therapeutic targets.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
Dear Editor,We present a modified surgical technique to verify the chorion layer of the human amniotic membrane(hAM)in treating retinal detachment(RD)with vitrectomy.RD patients with pathological myopia where the tear...Dear Editor,We present a modified surgical technique to verify the chorion layer of the human amniotic membrane(hAM)in treating retinal detachment(RD)with vitrectomy.RD patients with pathological myopia where the tear is located within the posterior pole choroidal atrophy area are difficult to treat.Surgical procedures such as laser treatments,diathermy,cryopexy applications or long-term silicone oil endotamponade may not only be ineffective but also harmful in these cases^([1]).Amniotic membrane transplantation(AMT)is an effective technique in case of RD recurrences to seal retinal holes over high myopic chorioretinal atrophy^([2]).展开更多
Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using mic...Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using microscope-integrated Optical Coherence Tomography with deep learning.Five convolutional neural networks with different architectures were evaluated.The main differences between the architectures are the amount of information they receive at the input layer.When evaluated on ex-vivo pig eyes,the top performing network successfully detected all needles in the dataset and localised them with an Intersection over Union value of 0.55.The algorithm was evaluated by comparing the depth of the top and bottom edge of the predicted bounding box to the ground truth.This analysis showed that the top edge can be used to predict the depth of the needle with a maximum error of 8.5μm.展开更多
AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich pe...AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.展开更多
AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injecti...AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells(PECs) and the local expression of TGF-β isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) at various time points.In addition,we investigated the effect of TFG-β-neutralizing antibodies(TGF-β NAb) on subretinal fibrosis development.· RESULTS:TGF-β1 and TGF-β2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5,reaching the peak.TGF-β3 mRNA was not detected in the present study.The result of ELSIA showed that active TGF-β1 and TGF-β2 levels were upregulated to 10-fold approximately,while total TGF-β1 and TGF-β2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with na?觙ve mice at day 5.TGF-β NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.· CONCLUSION:Our results indicate that TGF-β signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-β inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.·展开更多
AIM:To provide a detailed description of the natural history of persistent subretinal fluid(SRF)after successful repair of rhegmatogenous retinal detachment(RRD)and its association with visual outcome.METHODS:This was...AIM:To provide a detailed description of the natural history of persistent subretinal fluid(SRF)after successful repair of rhegmatogenous retinal detachment(RRD)and its association with visual outcome.METHODS:This was a prospective long-term follow-up for eyes undergoing scleral buckling(SB)surgery for maculaoff RRD.Examinations were carried out preoperatively and postoperatively at 1,3,6,9 and 12 mo,until persistent SRF had completely resolved.One month postoperatively,optical coherence tomography(OCT)was used to classify SRF into three patterns:bleb-like loculated(BL),shallow-diffused(SD),and multiple blebs(MB).Serial OCT imaging was used to evaluate morphological changes in SRF until its complete disappearance.Patients were divided into two groups depending on the presence or absence of persistent SRF.RESULTS:A total of 59 patients(59 eyes)were included.There were no statistical differences between two groups at baseline,except for the proportion of patients with high myopia and a younger age.One month after surgery,OCT detected persistent SRF in 49 eyes(83.1%).The 3 morphological patterns of SRF were observed in 27 eyes(55.1%)with BL,13 eyes(26.5%)with SD,and 9 eyes(18.4%)with MB.The mean time for complete absorption differed significantly across the three SRF patterns(F=8.097,P=0.001),which was 8.8±6.1,20.1±12.1,and 16.7±10.2 mo in BL,SD,and MB,respectively.In 9 of the 13 eyes with SD,the pattern transformed into MB type.In cases involving MB,the size and number of blebs decreased gradually until they had been completely absorbed.Eyes with persistent SRF were more likely to demonstrate disruption of the ellipsoid zone(49.0%vs 10%,P=0.034).The final best-corrected visual acuity of two groups was 0.37±0.11(with SRF)vs 0.34±0.12(without SRF)logMAR(P=0.499),respectively.CONCLUSION:High preoperative myopia and younger age are associated with persistent SRF.BL is the most commonly observed pattern with the shortest duration and gradually disappeared.Most cases involving SD SRF transform into MB type during resolution.The size and number of the MBs decrease gradually until they were completely absorbed.The absence of persistent SRF may contribute to slow visual recovery in the short-term but does not influence the final visual outcome.展开更多
AIM: To assess surgical outcomes of a novel method of transscleral drainage of subretinal fluid using a 25-gauge trocar-cannula with a self-closing valve(DTV) in patients with severe exudative retinal detachment(ERD) ...AIM: To assess surgical outcomes of a novel method of transscleral drainage of subretinal fluid using a 25-gauge trocar-cannula with a self-closing valve(DTV) in patients with severe exudative retinal detachment(ERD) in Coats disease.METHODS: Retrospective consecutive cases of 20 patients(20 eyes) of severe ERD due to Coats disease(stage 3 B) in total 156 Coats patients between June 2015 and April 2019 were included in this study. The participants were aged 1 to 10 y with a mean age of 3.50±1.79 y. The mean follow-up time were 11.9 mo. Subretinal fluid was drained transsclerally using a novel method of DTV. The height of the retinal detachment and the regression of abnormal vessels including telangiectasias and aneurysms were observed. Complications including vitreoretinal fibrosis, tractional retinal detachments(TRD), endophthalmitis, retinal holes, and hemorrhages were evaluated.RESULTS: Following surgeries, the patients showed the replacement of ERD and regression of telangiectatic retinal vessels observed with binocular indirect ophthalmoscopy. Six patients received retinal cryotherapies and 12 patients received laser photocoagulations following first external subretinal fluid drainage using DTV. All patients underwent intravitreal anti-vascular endothelial growth factor therapies to induce residual subretinal fluid absorption. During followups, 8 patients underwent a second drainage operation, 17 patients received retinal laser photocoagulations and 7 patients received cryotherapies. Vitreoretinal fibrosis was found in 7 patients and 6 patients underwent microinvasive vitrectomies during the follow-up period. Severe TRD, iatrogenic retinal holes, and hemorrhages were not found.CONCLUSION: The authors present a new therapeutic approach that successfully drains subretinal fluid in advanced stage 3 B Coats disease with severe ERD. This is a simple, safe and less invasive approach when compared with traditional managements. However, it should be strictly selected for patients with high bullous ERD close to the central axis of the eye in order to avoid the complication of retinal holes.展开更多
AIM:To investigate whether anti-placental growth factor(PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition(EMT) of retinal pig...AIM:To investigate whether anti-placental growth factor(PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition(EMT) of retinal pigment epithelial(RPE) cells.METHODS:Subretinal fibrosis model was established in laser induced choroidal neovascularization(CNV) mice on day 21 after laser photocoagulation.Immunofluorescence staining(IFS) of cryosections and enzyme-linked immunosorbent assay(ELISA) were used to detect the expression of PGF.IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis.IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.RESULTS:The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated(P<0.05),and mainly co-stained with pan-cytokeratin labeled RPE cells.Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25,0.5,1.0,and 2.0 μg/μL(all P<0.05).The expression of E-cadherin in the local RPE cells decreased,while α-SMA increased significantly in subretinal fibrosis lesions,and the application of anti-PGF neutralizing antibody could reverse these changes(P<0.05).CONCLUSION:The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells.Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice,and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.展开更多
The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transpl...The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells （RPCs） were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.展开更多
Diabetic maculopathy with marked exudation may lead to subretinal fibrosis. Two patients observed over multiple years evolved from macular exudation into subretinal fibrosis with severe visual loss. Spectral domain op...Diabetic maculopathy with marked exudation may lead to subretinal fibrosis. Two patients observed over multiple years evolved from macular exudation into subretinal fibrosis with severe visual loss. Spectral domain optical coherence tomography and color photographs document the clinical changes.展开更多
Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from th...Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from the central macula, ideally within 7 to 10 days after onset, is critical to allowing potential recovery of vision. Surgical techniques with the use of a bubble to displace the subretinal hemorrhage can now be performed with tissue plasminogen activator to lyze the blood and with or without vitrectomy.展开更多
Subretinal inflammation plays a critical role in retinal degenerative diseases.Although activated macrophages have been shown to play a key role in the progression of retinopathies and specifically in age-related macu...Subretinal inflammation plays a critical role in retinal degenerative diseases.Although activated macrophages have been shown to play a key role in the progression of retinopathies and specifically in age-related macular degeneration,little is known about the mechanisms involved in the loss of photoreceptors leading to vision impairment.In our study on retinal damages induced by photo-oxidative stress,we have observed that CD36-deficient mice featured less subretinal macrophage accumulation with attenuated photoreceptor degeneration compared to wild-type(WT)mice.Treatment with CD36-selective azapeptide ligand(labelled MPE-001)as modulator of the inflammatory environment of the retina reduced subretinal macrophage/activated microglia accumulation with preservation of photoreceptor layers and function assessed by ERG in WT,in a CD36-dependent manner.The azapeptide modulated the transcriptome of subretinal macrophage/activated microglia by reducing pro-inflammatory markers.In isolated macrophages,the CD36-selective azapeptide induced dissociation of the CD36-TLR2/6 heterodimer complex(using FRET)altering the TLR2 signaling pathway,thus decreasing NF-κB activation and inflammasome activity.The azapeptide also incurred cytoprotection against photoreceptor apoptosis elicited by activated macrophages.These findings suggest that the azapeptide as ligand of co-receptor CD36 decreases the inflammatory response by modulating CD36-TLR2/6 complex signaling pathway in macrophages,and suggests its potential application in the treatment of retinal degenerative diseases.展开更多
Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically dev...Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically devoid of MPs and a zone of immune privilege mediated,among others,by immunosuppressive RPE signals.Age-related macular degeneration(AMD)is a highly heritable major cause of blindness,characterized by a breakdown of the subretinal immunosuppressive environment and an accumulation of pathogenic inflammatory MPs.Studies in mice and humans suggest that the AMD-associated APOE2 isoform promotes the breakdown of subretinal immunosuppression and increased MP survival.Of all genetic factors,variants of complement factor H(CFH)are associated with greatest linkage to AMD.Using loss of function genetics and orthologous models of AMD,we provide mechanistic evidence that CFH inhibits the elimination of subretinal MPs.Importantly,the AMD-associated CFH402H isoform markedly increased this inhibitory effect on microglial cells,indicating a causal link to disease etiology.Pharmacological acceleration of resolution of subretinal inflammation might be a powerful tool for controlling inflammation and neurodegeneration in late AMD.展开更多
Background After successful scleral buckle and cryotherapy for macular-off retinal detachment （RD）, some patients have poor visual acuity without any clinically detected macular change, and the unsatisfactory postop...Background After successful scleral buckle and cryotherapy for macular-off retinal detachment （RD）, some patients have poor visual acuity without any clinically detected macular change, and the unsatisfactory postoperative visual acuity is difficult to explain. The purpose of this study was to determine the characteristics of subretinal fluid （SRF） after successful scleral buckle surgery for macula-off RD. Methods Twenty-eight eyes from 28 patients were included in this study. The patients underwent scleral buckle surgery combined with cryopexy for macular-off RD. After surgery, all eyes underwent thorough ophthalmologic examinations including slit-lamp biomicroscopy, best-corrected visual acuity （BCVA） test, and binocular indirect ophthalmoscopy. The BCVA prior to the operation, duration of RD, the duration of postoperative retinal reattachment, BCVA when SRF was observed, period required for the SRF to become undetectable, and the BCVA at the final follow-up were included in the clinical data for this study. Optical coherence tomography （OCT） and B-ultrasonography were used to confirm SRF, and fluorescein angiography （FFA） was carried out in several patients. BCVA when SRF was observed and BCVA at the final follow-up were evaluated using a paired t test. Correlations between BCVA before the operation and duration of RD and BCVA at the final follow-up were analyzed using the Pearson correlation test. The type of SRF under OCT and BCVA at the final follow-up were compared using one-way analysis of variance （ANOVA）. Results Postoperative retinal reattachment was achieved in 1.0-7.0 days （average, （2.7±.2.1） days）. After retinal reattachment, SRF was detected in all eyes by OCT 2 weeks postoperative, while B ultrasonography found no changes. The mean IogMAR BCVA was 0.35±0.27 at the time of the detection of SRF. The period for SRF to become undetectable ranged from 2.0 to 11.0 months （average, （6.3±2.3） months）. The time of follow-up ranged from 24.0 to 36.0 months （average, （28.9±3.4） months）. The mean IogMAR BCVA improved to 0.30±0.23 at the final follow-up, which was significantly different from the mean IogMAR BCVA at the time of SRF detection （paired t-test, t=3.82, P 〈0.05）. Postoperative OCT images were classified into three categories. FFA was carried out in 10 eyes and revealed no leakage or strain in the lesions. BCVA before the operation was significantly correlated with BCVA at the final follow-up （r=0.56, P 〈0.05）. No significant correlation was observed between BCVA at the final follow-up and duration of RD （r=0.23, P=0.22）. One-way analysis of variance （ANOVA） showed no significant difference between the type of SRF under OCT and BCVA at the final follow-up （F=0.21, P=0.81）. Conclusions The presence of persistent SRF after successful scleral buckle surgery for macular-off rhegmatogenous RD may influence the BCVA or anatomic attachment. SRF was detected in all eyes by OCT at 2 weeks after the operation Residual detachment persisted for almost a year after surgery in certain patients. Fluorescein angiography revealed no leakage or strain in the lesions.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
AIM:To evaluate the effectiveness of 532,577,and 810 nm lasers as an initial treatment for non-resolving central serous chorioretinopathy(CSC).METHODS:Following the Cochrane Collaboration Handbook and Preferred Report...AIM:To evaluate the effectiveness of 532,577,and 810 nm lasers as an initial treatment for non-resolving central serous chorioretinopathy(CSC).METHODS:Following the Cochrane Collaboration Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)guidelines,randomized clinical trials(RCTs),non-randomized cohorts,observational studies,and case series(>10 cases)assessing these lasers for non-resolving CSC with≥3mo of follow-up were included.Non-resolving CSC was defined as persistent subretinal fluid(SRF)for>3-6mo.Searches were conducted in PubMed,the Cochrane Library,and Embase(January 17,2025).Two authors independently performed data extraction and assessed the risk of bias.The primary outcome was SRF resolution on optic cherence tomography(OCT)at 3-6mo.Central retinal thickness(CRT)and best-corrected visual acuity(BCVA)were secondary outcomes.A random-effects model was employed to calculate pooled proportions with 95%confidence intervals(CIs),and heterogeneity was assessed using I²and Q statistics.RESULTS:Twenty-four studies(3 RCTs,21 non-RCTs)involving 829 non-resolving CSC eyes(77.6%male,mean age 45.36y)were included.SRF resolution was 59%(95%CI:0.51-0.67;I2=72.6%),showing no significant difference between lasers.Trim-and-fill adjustment raised SRF resolution to 65%(95%CI:0.44-0.81).CRT significantly decreased by 126.32µm(95%CI:95.99-156.65;P<0.0001;I2=95.7%),with the largest reduction noted for the 810 nm laser.BCVA change was 0.10 logMAR(95%CI:-0.03 to 0.22;P=0.13;I2=96.6%),indicating no significant visual improvement.CONCLUSION:This Meta-analysis supports the use of 532,577,and 810 nm subthreshold micropulse lasers as equally effective in resolving SRF in non-resolving CSC.展开更多
AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trau...AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.展开更多
AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conduc...AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit,spectral domain optical coherence tomography(SD-OCT)imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy.RESULTS: A total of 17 eyes of 13 patients treated with25 and 50 mg of oral eplerenone per day were identified.Subretinal fluid(SRF) decreased over time following eplerenone therapy(P = 0.007 and P =0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day181+. SRF diameter decreased from an average of 2174.4μm at baseline to 46.9 μm at day 181 +. Log MAR visual acuity improved from 0.42(Snellen equivalent: 20/53) at baseline to 0.29(Snellen equivalent: 20/39) at day 181 +(P = 0.024). Central subfield thickness(CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+(P = 0.029).CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.展开更多
Objective To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. Methods Detailed SD OCT an...Objective To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. Methods Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. Results Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. Conclusions Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.展开更多
文摘Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellular mechanisms,including inflammation,cell migration,and the activation of proliferative signaling pathways.One of the most challenging complications of RRD is proliferative vitreoretinopathy(PVR),which refers to the proliferation and contraction of fibrocellular membranes on the retinal surface and in the vitreous cavity.PVR is a major cause of surgical failure in RRD,as it can lead to recurrent retinal detachment and severe vision loss.However,the pathogenesis of PVR is not yet fully understood,and the treatment options are quite limited.Recent advances in analytical techniques have offered valuable insights into the molecular alterations present in the subretinal fluid(SRF)of patients with RRD.This review seeks to consolidate the current knowledge regarding the SRF profile in RRD and PVR,emphasizing potential biomarkers and therapeutic targets.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
文摘Dear Editor,We present a modified surgical technique to verify the chorion layer of the human amniotic membrane(hAM)in treating retinal detachment(RD)with vitrectomy.RD patients with pathological myopia where the tear is located within the posterior pole choroidal atrophy area are difficult to treat.Surgical procedures such as laser treatments,diathermy,cryopexy applications or long-term silicone oil endotamponade may not only be ineffective but also harmful in these cases^([1]).Amniotic membrane transplantation(AMT)is an effective technique in case of RD recurrences to seal retinal holes over high myopic chorioretinal atrophy^([2]).
基金ZJU 100 Young Talent ProgramKey Program for Robot-assisted Subretinal Injection Research Center in Zhejiang Province,Grant/Award Number:2023ZY1061。
文摘Subretinal injection is a complicated task for retinal surgeons to operate manually.In this paper we demonstrate a robust framework for needle detection and localisation in robotassisted subretinal injection using microscope-integrated Optical Coherence Tomography with deep learning.Five convolutional neural networks with different architectures were evaluated.The main differences between the architectures are the amount of information they receive at the input layer.When evaluated on ex-vivo pig eyes,the top performing network successfully detected all needles in the dataset and localised them with an Intersection over Union value of 0.55.The algorithm was evaluated by comparing the depth of the top and bottom edge of the predicted bounding box to the ground truth.This analysis showed that the top edge can be used to predict the depth of the needle with a maximum error of 8.5μm.
基金Supported by Liaoning Science and Technology Project(No.2013225303)
文摘AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.
文摘AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells(PECs) and the local expression of TGF-β isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) at various time points.In addition,we investigated the effect of TFG-β-neutralizing antibodies(TGF-β NAb) on subretinal fibrosis development.· RESULTS:TGF-β1 and TGF-β2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5,reaching the peak.TGF-β3 mRNA was not detected in the present study.The result of ELSIA showed that active TGF-β1 and TGF-β2 levels were upregulated to 10-fold approximately,while total TGF-β1 and TGF-β2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with na?觙ve mice at day 5.TGF-β NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.· CONCLUSION:Our results indicate that TGF-β signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-β inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.·
文摘AIM:To provide a detailed description of the natural history of persistent subretinal fluid(SRF)after successful repair of rhegmatogenous retinal detachment(RRD)and its association with visual outcome.METHODS:This was a prospective long-term follow-up for eyes undergoing scleral buckling(SB)surgery for maculaoff RRD.Examinations were carried out preoperatively and postoperatively at 1,3,6,9 and 12 mo,until persistent SRF had completely resolved.One month postoperatively,optical coherence tomography(OCT)was used to classify SRF into three patterns:bleb-like loculated(BL),shallow-diffused(SD),and multiple blebs(MB).Serial OCT imaging was used to evaluate morphological changes in SRF until its complete disappearance.Patients were divided into two groups depending on the presence or absence of persistent SRF.RESULTS:A total of 59 patients(59 eyes)were included.There were no statistical differences between two groups at baseline,except for the proportion of patients with high myopia and a younger age.One month after surgery,OCT detected persistent SRF in 49 eyes(83.1%).The 3 morphological patterns of SRF were observed in 27 eyes(55.1%)with BL,13 eyes(26.5%)with SD,and 9 eyes(18.4%)with MB.The mean time for complete absorption differed significantly across the three SRF patterns(F=8.097,P=0.001),which was 8.8±6.1,20.1±12.1,and 16.7±10.2 mo in BL,SD,and MB,respectively.In 9 of the 13 eyes with SD,the pattern transformed into MB type.In cases involving MB,the size and number of blebs decreased gradually until they had been completely absorbed.Eyes with persistent SRF were more likely to demonstrate disruption of the ellipsoid zone(49.0%vs 10%,P=0.034).The final best-corrected visual acuity of two groups was 0.37±0.11(with SRF)vs 0.34±0.12(without SRF)logMAR(P=0.499),respectively.CONCLUSION:High preoperative myopia and younger age are associated with persistent SRF.BL is the most commonly observed pattern with the shortest duration and gradually disappeared.Most cases involving SD SRF transform into MB type during resolution.The size and number of the MBs decrease gradually until they were completely absorbed.The absence of persistent SRF may contribute to slow visual recovery in the short-term but does not influence the final visual outcome.
基金Supported by Beijing Tongren Hospital,Capital Medical University(No.TRZDYXZY201703)
文摘AIM: To assess surgical outcomes of a novel method of transscleral drainage of subretinal fluid using a 25-gauge trocar-cannula with a self-closing valve(DTV) in patients with severe exudative retinal detachment(ERD) in Coats disease.METHODS: Retrospective consecutive cases of 20 patients(20 eyes) of severe ERD due to Coats disease(stage 3 B) in total 156 Coats patients between June 2015 and April 2019 were included in this study. The participants were aged 1 to 10 y with a mean age of 3.50±1.79 y. The mean follow-up time were 11.9 mo. Subretinal fluid was drained transsclerally using a novel method of DTV. The height of the retinal detachment and the regression of abnormal vessels including telangiectasias and aneurysms were observed. Complications including vitreoretinal fibrosis, tractional retinal detachments(TRD), endophthalmitis, retinal holes, and hemorrhages were evaluated.RESULTS: Following surgeries, the patients showed the replacement of ERD and regression of telangiectatic retinal vessels observed with binocular indirect ophthalmoscopy. Six patients received retinal cryotherapies and 12 patients received laser photocoagulations following first external subretinal fluid drainage using DTV. All patients underwent intravitreal anti-vascular endothelial growth factor therapies to induce residual subretinal fluid absorption. During followups, 8 patients underwent a second drainage operation, 17 patients received retinal laser photocoagulations and 7 patients received cryotherapies. Vitreoretinal fibrosis was found in 7 patients and 6 patients underwent microinvasive vitrectomies during the follow-up period. Severe TRD, iatrogenic retinal holes, and hemorrhages were not found.CONCLUSION: The authors present a new therapeutic approach that successfully drains subretinal fluid in advanced stage 3 B Coats disease with severe ERD. This is a simple, safe and less invasive approach when compared with traditional managements. However, it should be strictly selected for patients with high bullous ERD close to the central axis of the eye in order to avoid the complication of retinal holes.
基金Supported by the Shaanxi Key Research and Development Program-General Project in the Field of Social Development (No.2017SF-140)。
文摘AIM:To investigate whether anti-placental growth factor(PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition(EMT) of retinal pigment epithelial(RPE) cells.METHODS:Subretinal fibrosis model was established in laser induced choroidal neovascularization(CNV) mice on day 21 after laser photocoagulation.Immunofluorescence staining(IFS) of cryosections and enzyme-linked immunosorbent assay(ELISA) were used to detect the expression of PGF.IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis.IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.RESULTS:The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated(P<0.05),and mainly co-stained with pan-cytokeratin labeled RPE cells.Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25,0.5,1.0,and 2.0 μg/μL(all P<0.05).The expression of E-cadherin in the local RPE cells decreased,while α-SMA increased significantly in subretinal fibrosis lesions,and the application of anti-PGF neutralizing antibody could reverse these changes(P<0.05).CONCLUSION:The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells.Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice,and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.
文摘The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells （RPCs） were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.
文摘Diabetic maculopathy with marked exudation may lead to subretinal fibrosis. Two patients observed over multiple years evolved from macular exudation into subretinal fibrosis with severe visual loss. Spectral domain optical coherence tomography and color photographs document the clinical changes.
文摘Subretinal hemorrhage is a vision threatening complication of exudative age related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV). Timely removal or displacement of subretinal hemorrhage from the central macula, ideally within 7 to 10 days after onset, is critical to allowing potential recovery of vision. Surgical techniques with the use of a bubble to displace the subretinal hemorrhage can now be performed with tissue plasminogen activator to lyze the blood and with or without vitrectomy.
文摘Subretinal inflammation plays a critical role in retinal degenerative diseases.Although activated macrophages have been shown to play a key role in the progression of retinopathies and specifically in age-related macular degeneration,little is known about the mechanisms involved in the loss of photoreceptors leading to vision impairment.In our study on retinal damages induced by photo-oxidative stress,we have observed that CD36-deficient mice featured less subretinal macrophage accumulation with attenuated photoreceptor degeneration compared to wild-type(WT)mice.Treatment with CD36-selective azapeptide ligand(labelled MPE-001)as modulator of the inflammatory environment of the retina reduced subretinal macrophage/activated microglia accumulation with preservation of photoreceptor layers and function assessed by ERG in WT,in a CD36-dependent manner.The azapeptide modulated the transcriptome of subretinal macrophage/activated microglia by reducing pro-inflammatory markers.In isolated macrophages,the CD36-selective azapeptide induced dissociation of the CD36-TLR2/6 heterodimer complex(using FRET)altering the TLR2 signaling pathway,thus decreasing NF-κB activation and inflammasome activity.The azapeptide also incurred cytoprotection against photoreceptor apoptosis elicited by activated macrophages.These findings suggest that the azapeptide as ligand of co-receptor CD36 decreases the inflammatory response by modulating CD36-TLR2/6 complex signaling pathway in macrophages,and suggests its potential application in the treatment of retinal degenerative diseases.
文摘Mononuclear phagocytes(MP)comprise a family of cells that include microglial cells(MC),monocytes,and macrophages.The subretinal space,located between the RPE and the photoreceptor outer segments,is physiologically devoid of MPs and a zone of immune privilege mediated,among others,by immunosuppressive RPE signals.Age-related macular degeneration(AMD)is a highly heritable major cause of blindness,characterized by a breakdown of the subretinal immunosuppressive environment and an accumulation of pathogenic inflammatory MPs.Studies in mice and humans suggest that the AMD-associated APOE2 isoform promotes the breakdown of subretinal immunosuppression and increased MP survival.Of all genetic factors,variants of complement factor H(CFH)are associated with greatest linkage to AMD.Using loss of function genetics and orthologous models of AMD,we provide mechanistic evidence that CFH inhibits the elimination of subretinal MPs.Importantly,the AMD-associated CFH402H isoform markedly increased this inhibitory effect on microglial cells,indicating a causal link to disease etiology.Pharmacological acceleration of resolution of subretinal inflammation might be a powerful tool for controlling inflammation and neurodegeneration in late AMD.
文摘Background After successful scleral buckle and cryotherapy for macular-off retinal detachment （RD）, some patients have poor visual acuity without any clinically detected macular change, and the unsatisfactory postoperative visual acuity is difficult to explain. The purpose of this study was to determine the characteristics of subretinal fluid （SRF） after successful scleral buckle surgery for macula-off RD. Methods Twenty-eight eyes from 28 patients were included in this study. The patients underwent scleral buckle surgery combined with cryopexy for macular-off RD. After surgery, all eyes underwent thorough ophthalmologic examinations including slit-lamp biomicroscopy, best-corrected visual acuity （BCVA） test, and binocular indirect ophthalmoscopy. The BCVA prior to the operation, duration of RD, the duration of postoperative retinal reattachment, BCVA when SRF was observed, period required for the SRF to become undetectable, and the BCVA at the final follow-up were included in the clinical data for this study. Optical coherence tomography （OCT） and B-ultrasonography were used to confirm SRF, and fluorescein angiography （FFA） was carried out in several patients. BCVA when SRF was observed and BCVA at the final follow-up were evaluated using a paired t test. Correlations between BCVA before the operation and duration of RD and BCVA at the final follow-up were analyzed using the Pearson correlation test. The type of SRF under OCT and BCVA at the final follow-up were compared using one-way analysis of variance （ANOVA）. Results Postoperative retinal reattachment was achieved in 1.0-7.0 days （average, （2.7±.2.1） days）. After retinal reattachment, SRF was detected in all eyes by OCT 2 weeks postoperative, while B ultrasonography found no changes. The mean IogMAR BCVA was 0.35±0.27 at the time of the detection of SRF. The period for SRF to become undetectable ranged from 2.0 to 11.0 months （average, （6.3±2.3） months）. The time of follow-up ranged from 24.0 to 36.0 months （average, （28.9±3.4） months）. The mean IogMAR BCVA improved to 0.30±0.23 at the final follow-up, which was significantly different from the mean IogMAR BCVA at the time of SRF detection （paired t-test, t=3.82, P 〈0.05）. Postoperative OCT images were classified into three categories. FFA was carried out in 10 eyes and revealed no leakage or strain in the lesions. BCVA before the operation was significantly correlated with BCVA at the final follow-up （r=0.56, P 〈0.05）. No significant correlation was observed between BCVA at the final follow-up and duration of RD （r=0.23, P=0.22）. One-way analysis of variance （ANOVA） showed no significant difference between the type of SRF under OCT and BCVA at the final follow-up （F=0.21, P=0.81）. Conclusions The presence of persistent SRF after successful scleral buckle surgery for macular-off rhegmatogenous RD may influence the BCVA or anatomic attachment. SRF was detected in all eyes by OCT at 2 weeks after the operation Residual detachment persisted for almost a year after surgery in certain patients. Fluorescein angiography revealed no leakage or strain in the lesions.
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.
文摘AIM:To evaluate the effectiveness of 532,577,and 810 nm lasers as an initial treatment for non-resolving central serous chorioretinopathy(CSC).METHODS:Following the Cochrane Collaboration Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)guidelines,randomized clinical trials(RCTs),non-randomized cohorts,observational studies,and case series(>10 cases)assessing these lasers for non-resolving CSC with≥3mo of follow-up were included.Non-resolving CSC was defined as persistent subretinal fluid(SRF)for>3-6mo.Searches were conducted in PubMed,the Cochrane Library,and Embase(January 17,2025).Two authors independently performed data extraction and assessed the risk of bias.The primary outcome was SRF resolution on optic cherence tomography(OCT)at 3-6mo.Central retinal thickness(CRT)and best-corrected visual acuity(BCVA)were secondary outcomes.A random-effects model was employed to calculate pooled proportions with 95%confidence intervals(CIs),and heterogeneity was assessed using I²and Q statistics.RESULTS:Twenty-four studies(3 RCTs,21 non-RCTs)involving 829 non-resolving CSC eyes(77.6%male,mean age 45.36y)were included.SRF resolution was 59%(95%CI:0.51-0.67;I2=72.6%),showing no significant difference between lasers.Trim-and-fill adjustment raised SRF resolution to 65%(95%CI:0.44-0.81).CRT significantly decreased by 126.32µm(95%CI:95.99-156.65;P<0.0001;I2=95.7%),with the largest reduction noted for the 810 nm laser.BCVA change was 0.10 logMAR(95%CI:-0.03 to 0.22;P=0.13;I2=96.6%),indicating no significant visual improvement.CONCLUSION:This Meta-analysis supports the use of 532,577,and 810 nm subthreshold micropulse lasers as equally effective in resolving SRF in non-resolving CSC.
基金Supportea by DeNardo Education and Research Foundation GrantJeffrey T.Fort Innovation Fund+3 种基金Siteman Retina Research FundResearch to Prevent Blindness IncGetahun H is supported by Washington University in St.Louis School of Medicine Dean’s Medical Student Research Fellowship for the MD5 Yearlong Research ProgramGetahun H is also a recipient of a Research to Prevent Blindness Medical Student Eye Research Fellowship.
文摘AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.
文摘AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit,spectral domain optical coherence tomography(SD-OCT)imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy.RESULTS: A total of 17 eyes of 13 patients treated with25 and 50 mg of oral eplerenone per day were identified.Subretinal fluid(SRF) decreased over time following eplerenone therapy(P = 0.007 and P =0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day181+. SRF diameter decreased from an average of 2174.4μm at baseline to 46.9 μm at day 181 +. Log MAR visual acuity improved from 0.42(Snellen equivalent: 20/53) at baseline to 0.29(Snellen equivalent: 20/39) at day 181 +(P = 0.024). Central subfield thickness(CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+(P = 0.029).CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.
文摘Objective To provide novel spectral domain optical coherence tomography (SD OCT) findings of Vogt-Koyanagi-Harada (VKH) disease as well as new insights into the pathogenesis of this disease. Methods Detailed SD OCT and fluorescein angiography (FA) findings of 18 consecutive VKH patients (11 women and 7 men) from December 2007 to April 2009 who were in acute uveitic stage at presentation were reviewed. All the patients had been followed up for at least 6 months with reevaluation(s) of SD OCT performed in 10 patients. Results Intraretinal cysts were found to be located in various layers of the outer retina. In addition to the photoreceptor layer, they could also be found between the outer plexiform layer and the outer nuclear layer, or spanning the external limiting membrane. On FA, intraretinal cysts could be hypofluorescent, normofluorescent, or hyperfluorescent. Some intraretinal cysts had a characteristic FA pattern, in which a small round hypofluorescent area was surrounded by a ring of hyperfluorescence (donut-shaped dye pooling). Subretinal fibrinoid deposit appeared in acute uveitic stage in two severe VKH patients and seemed to develop from subretinal exudates and evolved into typical subretinal fibrosis. Gradual transfiguration/migration and progressive proliferation/pigmentation of the subretinal fibrinoid deposit/subretinal fibrosis was observed in one patient. Conclusions Intraretinal cysts could form in various layers of the outer retina and may result from extension of choroidal inflammation. Subretinal fibrosis may develop from subretinal exudates in VKH patients and may cause substantial visual impairment.
