Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

AIM:To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy(PVR)and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma.METHODS:Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus,followed by treatment with a slow-release dexamethasone implant(Ozurdex)or sham injection.Left eyes were used as normal controls.The intraocular pressure(IOP)was monitored using an iCare tonometer.PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk;specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction,Western blot,protein chip analysis,or immunofluorescence staining.RESULTS:During the observation period,PVR severity gradually increased.Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group.Ozurdex significantly alleviated PVR development and Müller cell gliosis.Post-traumatic inflammation fluctuated and was persistent.The interleukin-1β(IL-1β)mRNA level was significantly upregulated,peaking on day 3 and increasing again on day 21 after injury.The expression of nod-like receptor family pyrin domain containing 3(NLRP3)showed a similar trend that began earlier than that of IL-1βexpression.Ozurdex suppressed the expression of IL-1β,NLRP3,and phosphorylated nuclear factor-kappa B(NF-κB).The average IOP after treatment was within normal limits.CONCLUSION:The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk.Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis,and thus alleviates PVR severity.This study highlights the important role of IL-1β,and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1βinflammatory axis.In summary,Ozurdex provides a potential therapeutic option for traumatic PVR.

Proliferative vitreoretinopathy and its relationship with inflammatory serum biomarkers

AIM:To analyze if a relationship between levels ofinflammatory serum biomarkers and severity of primaryproliferative vitreoretinopathy(PVR)exists.METHODS:A retrospective case-control study.Thehealthy adult patients with rhegmatogenous retinaldetachment and primary PVR were included in the PVRgroup.For the control group,healthy adults who underwentcataract surgery were included.The grade of PVR wasclassified according to the Retinal Society TerminologyCommittee.Blood samples were obtained before surgery,and processed in MYTHIC 18.Measures of interest wereneutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyteratio(PLR),and lymphocyte-to-monocyte ratio(LMR),thetime between the decrease in visual acuity and surgery,PVRgrade,type of surgery,final best corrected visual acuity,andrate of re-detachment.RESULTS:Totally 240 patients were included,120 ineach group,79(65.8%)and 56(46.7%)were male in thePVR and control group,respectively.PVR A had greaterlevels of monocytes(0.28±0.18 vs 0.12±0.32,P=0.002),neutrophils(4.59±1.51 vs 3.92±1.27,P=0.006),and LMR(9.32±4.42 vs 7.43±3.90,P=0.01).PVR B had a greatermonocyte count(0.30±0.13 vs 0.12±0.32,P=0.001),andPVR C demonstrated higher levels in monocytes(0.27±0.12vs 0.12±0.32,P=0.004),neutrophils(4.39±1.13 vs3.92±1.27,P=0.004),and LMR(9.63±3.24 vs 7.43±3.90,P=0.002)compared to control,respectively.An LMR cut-offvalue of 9.38 predicted PVR with a sensibility of 54.2%andspecificity of 77.5%and NLR cut-off of 1.70 predicted PVRwith a sensibility of 62%and specificity of 54.2%.CONCLUSION:Patients with primary PVR demonstrategreater neutrophil,monocyte,and LMR levels than thecontrol group.Cut-off values obtained from ratios could beuseful in a clinical setting when no posterior view of thefundus is possible due to media opacity.

Anterior proliferative vitreoretinopathy in a patient with Coats disease

Dear Editor,I am Satoru Kase,from the Department of Ophthalmology,Faculty of Medicine and Graduate School of Medicine,Hokkaido University,Sapporo,Japan.I write to present a case of Coats disease showing anterior proliferative vitreoretinopathy（PVR）and neovascular glaucoma.

Effect of etanercept on post-traumatic proliferative vitreoretinopathy

AIM: To evaluate the safety and efficacy of intravitreal etanercept in the inhibiting of proliferative vitreoretinopathy(PVR) in a model of penetrating ocular injury. METHODS: Penetrating ocular injury on the retina of rabbit was induced, which was subsequently treated using 0.1 mL of sterile water or 0.1 m L of 12.5 mg/mL etanercept. The development of PVR was evaluated by fundus images, the B-scan, and the histopathology. The mRNA and protein expressions of tumor necrosis factor-α(TNF-α), transforming growth factor β(TGF-β) as well as connective tissue growth factor(CTGF) were examined at various time points after the etanercept injection with the reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blotting, respectively. The safety of etanercept was evaluated by injection of 12.5 mg/mL etanercept into a normal rabbit eye without penetrating trauma. RESULTS: Clinical assessment and grading clearly demonstrated that the PVR formation was prevented in etanercept-treated animals, which was confirmed via fundus images, B-scan and histopathology. The RT-PCR and Western blotting showed increased mRNA and protein expression of TNF-α, TGF-β as well as CTGF in the retina of rabbits following penetrating ocular injury, and these factors were dramatically mitigated by ocular etanercept treatment. In addition, there was no adverse effect of etanercept intravitreal injection in normal eyes without penetrating trauma, it showed normal structure and histology. CONCLUSION: The etanercept is a potential therapy for inhibiting PVR development. To assess the clinic application of the etanercept in preventing PVR, further clinical studies are required.

Expression of IGFBP-6 in a proliferative vitreoretinopathy rat model and its effects on retinal pigment epithelial cell proliferation and migration

AIM: To investigate the expression of insulin-like growth factor binding protein-6(IGFBP-6) in a proliferative vitreoretinopathy(PVR) model and its effects on proliferation and migration in retinal pigment epithelial(RPE) cells. ·METHODS: A PVR Wistar rat model was established by the intravitreal injection of RPE-J cells combined with platelet-rich plasma(PRP). The expression levels of IGFBP-6 were tested by ELISA. ARPE-19 cell proliferation was evaluated by the MTS method,and cell migration was evaluated by wound healing assays. ·RESULTS: The success rate of the PVR model was 89.3%(25/28). IGFBP-6 was expressed at higher levels in the vitreous,serum and retina of rats experiencing advanced PVR(grade 3) than in the control group(vitreous: 152.80 ±15.08ng/mL vs 105.44 ±24.81ng/mL,P 】 0.05; serum: 93.48 ±9.27ng/mL vs 80.59 ±5.20ng/mL,P 【 0.05; retina: 3.02±0.38ng/mg vs 2.05±0.53ng/mg,P 【0.05). In vitro,IGFBP-6(500ng/mL) inhibited the IGF-II(50ng/mL) induced ARPE-19 cell proliferation(OD value at 24h: from 1.38±0.05 to 1.30±0.02; 48h: from 1.44±0.06 to 1.35± 0.05). However,it did not affect basal or VEGF-,TGF-β-and PDGF-induced cell proliferation. IGFBP-6(500ng/ml) reduced the IGF-II(50ng/mL)-induced would healing rate [24h: from(43.91 ±3.85)% to(29.76 ±2.49)%; 48h: from(66.09±1.67)% to(59.88±3.43)%]. ·CONCLUSION: Concentrations of IGFBP-6 increased in the vitreous,serum,and retinas only in advanced PVR in vivo. IGFBP-6 also inhibited IGF-II-induced cell proliferation in a not dose or time dependent manner and migration. IGFBP-6 participates in the development of PVR and might play a protective role in PVR.

Outcomes and predictors of vitrectomy and silicone oil tamponade in retinal detachments complicated by proliferative vitreoretinopathy

AIM:To evaluate outcomes and determine factors influencing the outcomes of vitrectomy with silicone oil(SO)endotamponade for the management of rhegmatogenous retinal detachment(RRD)complicated by advanced proliferative vitreoretinopathy(PVR).METHODS:This is a retrospective,interventional case series of eyes with PVR grade C associated RRD with or without prior surgery that underwent vitreoretinal surgery and SO tamponade.Eyes with a minimum follow-up of 6mo after SO extraction were included.Eyes were classified into three PVR subgroups according to severity and extension of proliferation.The influence of several preoperative,intraoperative and postoperative factors upon the functional and anatomical outcomes was assessed using multivariate logistic regression analysis.RESULTS:A hundred and one eyes of 101 patients that met the inclusion criteria were studied.Seventy-five of 101 eyes(74.3%)had successful retinal reattachment after one operation.Increased aqueous cell and flare at the first week exam had a statistically significant association with redetachment,recurrent membrane proliferation and keratopathy.Visual acuity improvement was significantly associated with faint postoperative aqueous inflammation values,primary vitrectomy and PVR outside of the posterior pole.CONCLUSION:Although encouraging anatomical and functional outcomes are achieved after vitrectomy and SO tamponade in eyes with RRD complicated by PVR,an increase in aqueous flare or cells at the first week follow-up is most likely to result in postoperative late complications.Primary vitrectomy,PVR associated with minimal posterior pole extension and absent to mild postoperative aqueous inflammation are associated with improved post-operative final visual acuity.

Evaluating for Vitreous Surgery Used in Proliferative Vitreoretinopathy Grede D_3

Proliferative vitreoretinopathy (PVR) is one of the main failure causes of retinal detachment repair. In this paper, 25 cases of vitreous surgery used in the PVR D3 are analyzed. The diagnosis of PVR depended on the classification of the America Retina Society Terminology Committee. Vitrectomy and peeling were carried out in all of the patients. Intraocular tamponade included silicone oil and gas tamponade. Follow-up is more than 3 months. The anatomic successful rate was 68% and 11 cases arrived 20/400...

Upregulation of ASPP2 expression alleviates the development of proliferative vitreoretinopathy in a rat model

AIM:To investigate whether upregulation of apoptosisstimulating p53 protein 2(ASPP2)expression could alleviate the development of proliferative vitreoretinopathy(PVR)in a rat model.METHODS:ASPP2-lentivirus or scrambled-lentivirus were transfected into ARPE-19 cells,followed with measurements of cell cytotoxicity by cell counting kit-8 assay.ASPP2 upregulation was confirmed by Western blotting and immunocytochemistry.Then ARPE-19 cells pretreated with ASPP2-lentivirus were intravitreally injected to Brown Norway rats to induce PVR models.PVR development and retinal function were evaluated by retinal photography and electroretinography,respectively.Finally,epithelial-mesenchymal transition as well as autophagy were investigated in rats’retinas via Western blotting.RESULTS:Protein expression of ASPP2 was significantly upregulated by ASPP2-lentivirus transfection in ARPE-19 cells.The development and progression of PVR were impeded significantly in rats with intravitreal injection of ARPE-19 cells pretreated with ASPP2-lentivirus.Accordingly,retinal functions were less affected and PVR grades were much lower in rats with ASPP2-lentivirus compared to scrambledlentivirus treatment.Moreover,epithelial-mesenchymal transition and autophagy markers were decreased in the retinas of rats treated with ASPP2-lentivirus.CONCLUSION:ASPP2-lentivirus transfected to ARPE-19 cells mitigates the progression of PVR in rat models,which might be partly through reduced autophagy and attenuated epithelial-mesenchymal transition.ASPP2 might stand as a new approach for PVR treatment in the future.

What can we learn from negative results in clinical trials for proliferative vitreoretinopathy?

INTRODUCTION Since the beginning of vitreoretinal surgery proliferative vitreoretinopathy(PVR)has been a constant complication.PVR is the major cause for surgical failure after primary rhegmatogenous retinal detachment(RRD)resulting in multiple reoperations and vision loss.So far,there is no proven therapy to treat or prevent PVR.

Nomogram for predicting non-proliferative vitreoretinopathy probability after vitrectomy in eyes with rhegmatogenous retinal detachment

AIM:To identify the risk factors for postoperative proliferative vitreoretinopathy(PVR)in patients with primary rhegmatogenous retinal detachment(RRD)and develop a nomogram for predicting postoperative PVR-free probability.METHODS:A total of 741 patients(741 eyes)diagnosed with primary RRD who underwent first surgery in the same hospital were retrospectively reviewed and randomly assigned with 521 to the training set and 220 to the validation set.Univariate and multivariate logistic regression analyses were performed in the training cohort to determine risk factors to construct a nomogram for predicting the 3-,4-,5-,and 6-month postoperative PVR-free probabilities.Nomogram performance was estimated by the concordance index(C-index),calibration plot,and the area receiver operating characteristic(ROC)curve.RESULTS:A nomogram was constructed based on the preoperative PVR,silicone oil tamponade time(SOTT),photocoagulation energy(PE),retinal tear size(RTS),and hypertension.In the training set,the C-index of the nomogram was 0.896,0.936,0.961,and 0.972 at 3,4,5,and 6mo,respectively.The C-index values in the validation set were 0.860,0.936,0.951,and 0.965 at 3,4,5,and 6mo,respectively.Decision-curve analysis indicated that only the 4-,5-,and 6-month nomograms had significant net benefits over a large threshold probabilities interval.CONCLUSION:Preoperative PVR,SOTT,PE,RTS,and hypertension are significant risk factors for postoperative PVR formation in patients with primary RRD.The proposed nomogram can effectively predict the 4-,5-,and 6-month PVR-free probabilities after surgery and assist in making clinical decisions during follow-up.

Quantitative Study of Basic Fibroblast Growth Factor in Vitreous with Proliferative Vitreoretinopathy

Objective:To quantitatively study basic fibroblast growth factor(bFGF)in the vitreous ofproliferative vitreoretionopathy(PVR)inorder to understand the role of bFGFin the develop-ment of PVR.Method:High sensitive sandwich enzyme immunoassay technique(ELISA)was used to measure bFGF level in vitreous of normal eyes,the eyes of PVR-Cor pVR-Dgrade,eyes of vitreous hemorrhage and the serum levels of bFGF in PVR-Dpatients.Results:The levels of bFGF in the vitreous were:median5.20ng/L,quartile15.47ng/Lin20normal eyes;median3.12ng/L,quartile10.48ng/Lin35PVR-Ceyes;median46.56ng/L,quartile113.96ng/Lin26pPVR-Deyes;median1.40ng/L,quar-tile6.25ng/Lin25vitreous hemorrhage eyes.The vitreous bFGF level in PVR-D group was significantly higher than that in the normal group,PVR-Cgroup and vitreous hemorrhage group(P<0.01).The mean of serum-bFGFlevel was18.33±3.39ng/L.The vitreous bFGFlevel ofPVR-Dgroup was significantly higher than serum-bFGFlev-el(P<0.01).And the vitreous-bFGFlevel in PVR-Dgroup was significantly higher in larger retinal tear subgroup.Conclusion:The results suggested that bFGF is involved in the development of PVR.Eye Science2000;16:7-10.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

AIM:To analyze the distribution of fibrovascular proliferative membranes(FVPMs)in proliferative diabetic retinopathy(PDR)patients that treated with pars plana vitrectomy(PPV),and to evaluate the outcomes separately.METHODS:This was a retrospective and cross-sectional study.Consecutive 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April 2020.According to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type group.All patients were followed up for over one year.General characteristics,operation-related variables,postoperative parameters and complications were recorded.RESULTS:Among 103 eyes recruited,the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different(both P<0.01),with 95(92.23%)FVPMs located in the nasal quadrants,and 74(71.84%)in the inferior.The eyes with a central FVPM required the longest operation time,with silicon oil used in most patients,generally combined with tractional retinal detachment(RD)and rhegmatogenous RD,the worst postoperative bestcorrected visual acuity(BCVA)and the highest rates of recurrent RD(all P<0.05).FVPM type,age of onset diabetes mellitus,preoperative BCVA,and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement(all P<0.05).Compared with the central type group,the arcade type group had higher rates of BCVA improvement.CONCLUSION:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels.Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness(SFCT)in proliferative diabetic retinopathy(PDR).AIM To investigate the relationship between the SFCT and age in Chinese patients with PDR.METHODS This was a cross-sectional retrospective study.The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR.Contralateral eyes that met the criteria were included in the study.All necessary laboratory tests were performed at the time of admission.Central macular thickness(CMT)and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography.CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software.RESULTS The final analysis included a total of 234 individuals with PDR.The average age was 55.60 years old±10.03 years old,and 57.69%of the population was male.Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR[β=-2.44,95%confidence interval(95%CI):-3.46 to-1.42;P<0.0001].In the fully adjusted model,the correlation between SFCT and age remained steady(β=-1.68,95%CI:-2.97 to-0.39;P=0.0117).Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear,with an inflection point at 54 years of age.CONCLUSION Our findings suggest that age is a key determinant of choroidal thickness.The non-linear link between SFCT and age in PDR patients should be taken into account.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract:a randomized clinical trial

●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.

Cerebral proliferative angiopathy in pediatric age presenting as neurological disorders:A case report

BACKGROUND Cerebral proliferative angiopathy(CPA)is a rare subtype of arteriovenous malformation.It is extremely rare in pediatric patients and has serious implications for developing children.However,reports of these disorders worldwide are limited,and no uniform reference for diagnosis and treatment options exists.We report the case of a 6-year-old with CPA having predominantly neurological dysfunction and review the literature on pediatric CPA.CASE SUMMARY We report the case of a pediatric patient with CPA analyzed using digital subtraction angiography(DSA)who presented initially with a neurological disorder as the main manifestation.This case is the basis for further discussion of the clinical presentation,pathogenesis,diagnosis,and treatment of CPA in children.After the cerebral DSA,the patient was treated conservatively with sedation,fluid replacement,and blood anticoagulation.She could not cooperate with the followup magnetic resonance imaging examination because of her young age,and her family declined further treatment because of the surgery’s high risk.She was followed up for 3 months;her symptoms did not worsen.CONCLUSION This report of rare pediatric CPA can inform and advance clinical research on congenital cerebrovascular diseases.

Surgical treatment for proliferative diabetic retinopathy with ocular albinism

Dear Editor,We are writing to present an uncommon case of a45-year-old woman with bilateral proliferative diabetic retinopathy (PDR) and ocular albinism (OA).Albinism is a group of inherited disorders of tyrosinase activities and melanin biosynthesis resulting in little or no production of the pigment melanin。