Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

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.

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.

Application of immersion B-scan ultrasonography in diagnosis of complex retinal detachment,persistent hyperplastic primary vitreous and intraocular tumors

AIM:To evaluate the diagnostic value of panoramic immersion B-scan ultrasonography(Pano-immersion B-scan,PIB)in complex retinal detachment(RD),persistent hyperplastic primary vitreous(PHPV)and intraocular tumors.METHODS:The clinical data of 44 patients collected from May 2012 to December 2019 in Chinese PLA General Hospital was retrospectively studied.All of these patients underwent PIB of the eye,because it was difficult to diagnose by routine ocular fundus examination,conventional ultrasound or/and ultrasonic biomicroscope(UBM)due to opacity of refractive media,pupillary occlusion,large involvement or special location of the lesion.The imaging features of difficult cases in PIB were analyzed.The diagnosis accuracy rating of PIB were evaluated and contrasted with conventional ultrasound or UBM by the standard of intraoperative diagnosis or/and pathological results.RESULTS:According to intraoperative diagnosis or pathological results as gold standard,among the 44 cases,there were 19 cases missed diagnosis,misdiagnosed or difficult-to-diagnose by conventional ultrasound or UBM,including 4 cases of long-standing RD difficult to diagnose,4 cases misdiagnosed,and 11 cases incompletely observed or miss diagnosed.The diagnostic accuracy rate of PIB and conventional ultrasound or UBM were 100%(44/44)and 56.82%(25/44),and the sensitivity of them were 100%and 56.82%.All the patients underwent PIB and were diagnosed as RD(15 cases),retinal and choroidal detachment(4 cases),subchoroidal hematocele(1 case),vitreous opacity and/or organic membrane formation(4 cases),PHPV(12 cases),iris and/or ciliary body tumors(3 cases),and choroidal tumors(6 cases).According to the intraoperative diagnosis or pathological results,the diagnostic coincidence rate of PIB was 100%,which was significantly higher than conventional ultrasound and UBM.CONCLUSION:PIB can help to accurately diagnose complex RD,PHPV,and intraocular masses with special location or/and excessive size.It has important diagnostic value for patients with equivocal findings at conventional ultrasound examination.

Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome

Objective To investigate the clinical efficacy of dexamethasone vitreous cavity implants(Ozurdex)for the treatment of macular edema(Irvine-Gass Syndrome)after cataract surgery.Method Eight patients(eight eyes)with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex.The patients included six men(six eyes)and two women(two eyes)with a mean age of 67.12±11.92 years.Changes in the patients best-corrected visual acuity(BCVA),central macular thickness(CMT),and intraocular pressure were compared before and after treatment.Result The mean visual acuity BCVA of the patients was 0.81±0.26 before implantation,which improved to 0.20±0.12,0.13±0.09,and 0.15±0.13 at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).The patient’s mean CMT before implantation was 703.00±148.88μm,and it reduced to 258.87±37.40μm,236.25±28.74μm,and 278.00±76.82μm at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).Conclusion The dexamethasone vitreous cavity implant(Ozurdex)is a safe and effective treatment,which can effectively improve patient’s visual acuity and reduce macular edema associated with cataract surgery.

4D label-free proteomic analysis of vitreous from patients with rhegmatogenous retinal detachment

AIM:To identify metabolites,proteins,and related pathways involved in the etiology of rhegmatogenous retinal detachment(RRD)for use as biomarkers in diagnosing and treating RRD.METHODS:Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was per formed using the four-dimensional label-free technique.Statistically significant differentially expressed proteins,gene ontology(GO)terms,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representations,and protein interactions were analyzed.RESULTS:Nine specimens were subjected to proteomic analysis.In total,161 proteins were identified as differentially expressed proteins(DEPs),including 53 upregulated proteins and 108 downregulated proteins.GO functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein terms.Moreover,KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of DEPs.Finally,the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion,apoptosis,inflammation and immune responses,correct protein folding,and glycolysis.CONCLUSION:Proteomic profiling is useful for the exploration of molecular mechanisms that underlie RRD.This study reveals increased expression levels of proteins related to heat shock protein content,glycolysis,and inflammatory responses in RRD.Knowledge regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.

A novel approach for 25-gauge transconjunctival sutureless vitrectomy to evaluate vitreous substitutes in rabbits

AIM:To improve the standard three-port vitrectomy for establishing and evaluating an endotamponade model in rabbits.METHODS:Three ports were prepared near the third eyelid of rabbits,and the infusion port was placed at the inferior nasal quadrant with the inserted cannula linking with a self-designed handheld rigid infusion catheter.All right eyes of rabbits underwent a modified 25-gauge vitrectomy and were subsequently filled with balanced salt solution,silicone oil,and eight-arm polyethylene glycols(8-arm PEGs)hydrogel separately for comparison.Ophthalmic examinations were performed regularly to record the changes after the surgery.RESULTS:Successful vitrectomy was achieved among 44 chinchilla rabbits.The mean operation time was 4.51±1.25min.Four eyes(9.1%)presented limited lens touch and two eyes(4.5%)showed retinal touch during surgery.Incision leakage was found in three eyes(6.8%)after surgery.There was no endophthalmitis,hemorrhage,or retinal detachment during the observation period and ophthalmic examinations after the implantation of vitreous substitutes.CONCLUSION:The modified technique of the standard vitrectomy applied in the endotamponade model in rabbits shows excellent safety and practicality.

Expression levels of ROS and Atg proteins in the vitreous in rhegmatogenous retinal detachment

AIM:To detect the concentrations of reactive oxygen species(ROS),transient receptor potential mucin-1(TRPML1),and autophagy-related(Atg)proteins(LC3-Ⅰ,LC3-Ⅱ,and Beclin1)in vitreous humor of patients with simple rhegmatogenous retinal detachment(RRD).METHODS:RRD patients enrolled as the RRD group,and patients with idiopathic macular hole(IMH)and idiopathic macular epiretinal membrane(IMEM)were enrolled as control group.The levels of ROS,TRPML1,LC3-Ⅰ,LC3-Ⅱ,and Beclin1 in vitreous humor of patients in the RRD and control groups were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:The RRD group included 28 eyes 28 patients and had a higher concentration of ROS in vitreous humor(631.86±18.05 vs 436.34±108.22 IU/m L,P<0.05).The ROS level in patients with a wide retinal detachment(RD)extent(RD range≥1/2)was higher than that with a narrow RD extent(RD range<1/2,P<0.05).ROS concentration was negatively correlated with RD time(r=-0.46,P=0.01).The expression levels of LC3-Ⅰand Beclin1 significantly decreased in RRD(P<0.05),but there were no correlations with the RD time,RD extent,or macular involvement.CONCLUSION:In eyes with RRD,the concentration of ROS in vitreous humor increases and the expression levels of Atg proteins decrease,reflecting possibly that autophagy is inhibited.

Clinical Efficacy and Safety of Foldable Capsular Vitreous Body Implant Surgery in 22 Cases of Silicone Oil-dependent Eyes

Objective This study aimed to evaluate the clinical efficacy and safety of foldable capsular vitreous body(FCVB)implant surgery in silicone oil-dependent eyes.Methods A total of 22 participants with silicone oil-dependent eyes who received treatment with FCVB implant surgery between January 2019 and June 2020 were included in this retrospective study.The intraocular pressure(IOP),best-corrected visual acuity(BCVA),demographic data,and any recorded complications were evaluated.Results The postoperative IOP(12.73±4.20 mmHg)was significantly improved(P=0.03)compared to the preoperative IOP(10.23±3.69 mmHg)(the main endpoint).There was no significant difference(P=0.33)in the final BCVA preoperation and 3rd month postoperation(the secondary endpoint).The most common postoperative complication was hyphema.Other common postoperative complications included corneal opacity,a shallow anterior chamber,and a low IOP.Conclusion FCVB implant surgery is a safe and effective method for treating silicone oil-dependent eyes;however,attention should be paid to the prevention and timely treatment of complications.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin

AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment,without evidence of cardiac,renal,gastrointestinal,central nervous system or peripheral nervous system dysfunction.During the surgery,the patient presented with a gray-white dense and thick cotton woollike change in the vitreous body,accompanied by complete retinal detachment.Additionally,hard,free and movable yellow-white deposits were observed in the posterior pole and surrounding retina,the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination,and whole exome sequencing was performed on blood samples from the patient and her cousin.RESULTS:During the operation,it was discovered that there was a complete detachment of the retina and a significant amount of hard,free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina.This is an exceedingly rare ocular manifestation.Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining,as well as elevated vascular endothelial growth factor(VEGF)expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination.The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin(TTR)gene,resulting in a substitution of glycine(Gly)at position 103 with arginine(Arg).CONCLUSION:FVA may present with various ocular manifestations,but panretinal detachment is a rare occurrence.In cases where retinal detachment persists for an extended period of time,amyloid deposits may form under the retina through retinal tears,leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis.Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state,necessitating careful postoperative follow-up.The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

Investigation on the Shock Response of Vitreous Carbon

The dynamic response of vitreous carbon to uniaxial strain loading has been investigated by means of the plate impact experiments. The two x cut shorted quartz gauges assembled with impactor and target were used to obtain the wave speeds in material and the stress histories at the sample gauge interface. The wave speed and stress histories were analyzed to determine the peak state in the sample. For compressive stress up to 4 0 GPa, the wave profiles were observed to be simple and steady, the uniaxial strain response is essentially nonlinear elastic, and no inelastic deformation has been found. All the experiment results indicate that the Hugoniot curve of vitreous carbon is concave downward just like that of fused silicon. There is no shock wave but the compressed wave propagating in the impacted samples.

Vitreous substitutes: challenges and directions

The natural vitreous body has a fine structure and complex functions. The imitation of the natural vitreous body by vitreous substitutes is a challenging work for both researchers and ophthalmologists. Gases, silicone oil, heavy silicone oil and hydrogels, particularly the former two vitreous substitutes are clinically widely used with certain complications. Those, however, are not real artificial vitreous due to lack of structure and function like the natural vitreous body. This article reviews the situations, challenges, and future directions in the development of vitreous substitutes, particularly the experimental and clinical use of a new artificial foldable capsular vitreous body.

Prevalence of vitreous floaters in a community sample of smartphone users

AIM: To estimate the prevalence and risk factors for vitreous floaters in the general population. ·METHODS: An electronic survey was administered through a smartphone app asking various demographic and health questions, including whether users experience floaters in their field of vision. Multivariate logistic regression analysis was used to determine risk factors. ·RESULTS: A total of 603 individuals completed the survey, with 76% reporting that they see floaters, and 33% reporting that floaters caused noticeable impairment in vision. Myopes were 3.5 times more likely (P =0.0004), and hyperopes 4.4 times more likely (P =0.0069) to report moderate to severe floaters compared to those with normal vision. Floater prevalence was not significantly affected by respondent age, race, gender, and eye color. ·CONCLUSION: Vitreous floaters were found to be a very common phenomenon in this non -clinical general population sample, and more likely to be impairing in myopes and hyperopes.

Osteopontin expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy

AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained between 2009 and 2010, which contained 45 with PVR (group A) and 9 without PVR (group B). Enzyme-linked immunosorbent assay was applied to quantify the OPN concentrations in vitreous fluid. Four samples of proliferative retinal membrane were also obtained at the time of vitrectomy, and their contents of OPN were measured by Real-time RT-PCR. RESULTS: The OPN levels in the vitreous fluid were 778.48+/- 62.06ng/mL in group A and 452.99 32.52ng/mL in group B. The vitreous OPN levels in group A were significantly higher than those in group B and to rise by time in the early stages of PVR. The average OPN levels in the proliferative retinal membranes (F =0.14) were also higher than those in the retinal pigment cells (F =0) using Real-time RT-PCR. CONCLUSION: The high vitreous and proliferative retinal membrane OPN levels in PVR suggest that OPN might promote the development of PVR. The vitreous OPN concentrations are rising by the time in the early phases of PVR.

Long-term observation of vitrectomy without subretinal hemorrhage management for massive vitreous hemorrhage secondary to polypoidal choroidal vasculopathy

AIM: To describe the long-term observation of vitrectomy without subretinal hemorrhage(SRH) management for massive vitreous hemorrhage(VH) secondary to polypoidal choroidal vasculopathy(PCV). METHODS: This is a retrospective, consecutive case series. A total of 86 eyes of 86 patients with >14d of massive VH associated with PCV were included. All patients underwent vitrectomy without SRH management, followed by intravitreal ranibizumab injections and/or photodynamic therapy(PDT) as needed. The main outcome measures were best-corrected visual acuity(BCVA), postoperative adverse events and the recurrence of VH. RESULTS: The average follow-up period was 25.5±9.2 mo(range 12-35 mo). Mean BCVA at baseline(2.16±0.39 logM AR)had improved significantly, both 3 mo after surgery(1.42±0.66 log MAR, P<0.001) and by the last visit(1.23±0.74 logM AR, P<0.001). The common postoperative complications included macular subretinal fibrosis in 14 eyes(16.3%) and ciliary body detachment in 4 eyes(4.7%).Nineteen eyes(22.1%) received following treatment with ranibizumab injections without/with PDT, and 15(17.4%)were resolved. Four eyes(4.7%) had recurrent hemorrhage during the follow-up period. In multiple regression analysis,thicker SRH(beta=0.33, P=0.025) in the preoperative B-scan and the presence of foveal subretinal fibrosis(beta=0.28, P=0.018) in the follow up were associated with poor postoperative BCVA. CONCLUSION: Vitrectomy without SRH management for massive VH secondary to PCV improved/stabilized visual function in the long-term observation. Eyes presenting with thicker SRH preoperatively and forming foveal subretinal fibrosis in the follow-up period tended to have worse BCVA.

Vitrectomy for vitreous amyloidosis

AIM: To study the clinical features of vitreous amyloidosis and the effect of vitrectomy for it. METHODS: We treated 6 eyes (4 Patients) with vitreous amyloidosis from 2008 to 2009, and followed up for 18-30 months after vitrectomy. RESULTS: The visual acuity ranged from counting fingers to 3/50 before surgery and 15/50-40/50 after vitrectomy. No severe complication was observed. CONCLUSION: Vitrectomy is an effective and safe treatment for eyes with vitreous amyloidosis. A long period of follow-up after surgery should be performed.

Ultrasound reliability in detection of retinal tear in acute symptomatic posterior vitreous detachment with vitreous hemorrhage

Cross-sectional study of 75 consecutive patients presenting with acute symptomatic posterior vitreous detachment（ASPVD） and vitreous hemorrhage was conducted at University Eye Clinic,University Hospital ＂Sveti Duh＂,Zagreb,Croatia.To check ultrasound reliability in detecting retinal tears in patients with ASPVD,transpalpebral ultrasound of the eye and the orbit was performed followed by fundus examination initially and in 6 wk period.In 13（17%） patients membranous lesion with ultrasound characteristics of retinal tear was detected.Ophthalmoscopy confirmed the diagnosis in 8/13 patients.In 62/75 patients neither ultrasound nor clinical examination revealed retinal tear.Sensitivity of ultrasound examination was 100%,specificity 92%,positive predictive value 62% and negative predictive value 100%.Ultrasound proved to be a reliable and accurate method for detection of retinal tears in ASPVD.Given the high sensitivity and negative predictive value,negative result on B-scan ultrasound excludes the probability of the retinal tear with a high degree of certainty.

Effects of lens extirpation with anterior vitrectomy on vitreous three-dimensional mesh structure

AIM： To investigate the changes in vitreous gel structure after lens extirpation combined with anterior vitrectomy in rabbit eyes. METHODS： Twenty-eight chinchilla rabbits were divided into three groups. The control group （Group I） included 16 eyes from eight rabbits who did not receive any treatment. Group II included 20 eyes from 10 rabbits that underwent lens aspiration only. Group III included 20 eyes from 10 rabbits that underwent lens aspiration combined with posterior capsulotomy and anterior vitrectomy. Eyes were harvested on the 30th and 60th day postoperatively, respectively. Changes in vitreous gel stretch length due to gravity and the rate of vitreous liquefaction were observed. The collagen content in the vitreous body was examined using the L-hydroxyproiine test. Electronic microscopic images were obtained from each eyeball. RESULTS： On both the 30th and 60th day postoperatively, the vitreous gel length of group III was significantly shorter than group I and group II （P〈0.05）, while the rate of liquefaction of the vitreous body in group III was significantly higher than group I and group II （P〈0.05）. The collagen content in group Ul was also higher than that in group I and group II （P〈0.05）. CONCLUSION： Loss of vitreous gel mass is more likely to occur in the eyes of rabbits receiving anterior vitrectomy. Lensectomy combined with anterior vitrectomy may damage the stable three-dimensional mesh structure of collagen, which could aggravate vitreous gel liquefaction.

Endoscopy-assisted vitrectomy in the anterior vitreous

Endoscopy-assisted ocular surgery is a relatively old technique that is increasingly being recognized for its application in cases of vitreoretinal disease. This technique is especially useful when both the vitreous and retina are difficult to access because of media opacity, a small pupil, or a microcornea. In this context, the anterior vitreous is often difficult to dissect because of its complex pathological changes. This article reviews the common anatomical features and pathologies that are observed in the anterior vitreous, as well as the applications and indications of endoscopy-assisted vitrectomy in the anterior vitreous.

Molecules related to diabetic retinopathy in the vitreous and involved pathways

Diabetic retinopathy(DR)is one of the most common complications of diabetes and major cause of blindness among people over 50 years old.Current studies showed that the vascular endothelial growth factor(VEGF)played a central role in the pathogenesis of DR,and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization.However,anti-VEGF therapy has several limitations such as drug resistance.It is essential to develop new drugs for future clinical practice.The vitreous takes up 80%of the whole globe volume and is in direct contact with the retina,making it possible to explore the pathogenesis of DR by studying related factors in the vitreous.This article reviewed recent studies on DR-related factors in the vitreous,elaborating the VEGF upstream hypoxia-inducible factor(HIF)pathway and downstream pathways phosphatidylinositol diphosphate(PIP2),phosphoinositide-3-kinase(PI3 K),and mitogenactivated protein kinase(MAPK)pathways.Moreover,factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized,which included factors in four major systems,kallikrein-kinin system such as bradykinin,plasma kallikrein,and coagulation factor XII,oxidative stress system such as lipid peroxide,and superoxide dismutase,inflammation-related factors such as interleukin-1β/6/13/37,and interferon-γ,matrix metalloproteinase(MMP)system such as MMP-9/14.Additionally,we also introduced other DR-related factorssuch as adiponectin,certain specific amino acids,noncoding RNA and renin(pro)receptor in separate studies.