Intravitreal Injection Of anti-VEGF Drugs Research Articles

A review on vasohibin and ocular neovascularization.

Ischemic and neovascular disease is one of the most difficult ocular diseases to deal with nowadays. Redundancy, poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades. After vascular endothelial growth factor (VEGF) was found to be a primary factor in promoting retinal angiogenesis, intravitreal injection of anti-VEGF drugs has been the first-line treatment. Whereas, some patients are refractory to this therapy and problems of economic burden, local complications and adverse effects promote researches into other possible targets. The vasohibin (VASH) family is a newly-investigated factor in modulating ocular angiogenesis. The family includes VASH1 and VASH2, which show opposite effects of inhibiting and accelerating angiogenesis respectively. Positive results have been reported in cellular and animal experiments. With further researches, it can be a promising future target of treating ocular neovascular diseases.

Effectiveness of multistage surgical treatment of advanced proliferative diabetic retinopathy complicated with primary cataract

To evaluate the effectiveness of multistage surgical treatment of patients with advanced PDR complicated with primary cataract. The study involved 94 cases of surgical treatment of patients with PDR and complicated primary cataract. These patients were divided into two groups depending on the treatment tactics. In the first group, patients were subjected to a two-step surgical procedure: VRS with silicone oil tamponade performed as the first step in their treatment followed by phacoemulsification, silicone oil removal, and IOL implantation, respectively, as the second step. In subgroup 1a - VRS was performed with standard pharmacological support. In subgroup 1b - intravitreal injection of angiogenesis inhibitors preceded VRS. In the second group, the first step was phacoemulsification performed simultaneously with vitreoretinal surgery with silicone oil tamponade; the second step consisted of removing silicone oil from the vitreous cavity. Subgroup 2a - surgical treatment was performed with standard pharmacological support (similar to subgroup 1a). Subgroup 2b - intravitreal injection of anti-VEGF drugs preceded VRS. Visual functions improved in 88.8% and 83.4% of cases in subgroups 1a and 1b, and in 51.3% and 66.7% in subgroups 2a and 2b, respectively. The study confirms the effectiveness of staged (multi-step) surgical treatment of patients with advanced proliferative diabetic retinopathy and complicated primary cataract. Conducting phacoemulsification sometime later along with silicone oil removal in PDR patients with preoperative intravitreal injection of angiogenesis inhibitors is a gentler approach for the anatomic structures of the eye during the first stage (VRS) and contributes to the reduction in the number of intraoperative and postoperative complications.

Current status and progress of recurrence of retinopathy in prematurity after intravitreal injection with anti-vascular endothelial growth factor drugs

Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity(ROP) is a hot topic of research, and it can be used to treat the ROP (Ⅰzone). The current anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept and conbercept, etc. However, in recent years, several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy. The follow-up period should be extended and repeated injections may be required. Due to the lack of large-scale prospective clinical studies, the recurrence rate, time window of recurrence, risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear. Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence. Key words: Retinopathy of prematurity/drug therapy; Angiogenesis inhibitors/therapeutic use; Recurrence; Review

Anti-Angiogenic and Anti-Scarring Dual Action of an Anti-Fibroblast Growth Factor 2 Aptamer in Animal Models of Retinal Disease

Currently approved therapies for age-related macular degeneration (AMD) are inhibitors against vascular endothelial growth factor (VEGF), which is a major contributor to the pathogenesis of neovascular AMD (nAMD). Intravitreal injections of anti-VEGF drugs have shown dramatic visual benefits for AMD patients. However, a significant portion of AMD patients exhibit an incomplete response to therapy and, over the extended management course, can lose vision, with the formation of submacular fibrosis as one risk factor. We investigated a novel target for AMD treatments, fibroblast growth factor 2 (FGF2), which has been implicated in the pathophysiology of both angiogenesis and fibrosis in a variety of tissue and organ systems. The anti-FGF2 aptamer, RBM-007, was examined for treatment of nAMD in animal models. In in vivo studies conducted in mice and rats, RBM-007 was able to inhibit FGF2-induced angiogenesis, laser-induced choroidal neovascularization (CNV), and CNV with fibrosis. Pharmacokinetic studies of RBM-007 in the rabbit vitreous revealed high and relatively long-lasting profiles that are superior to other approved anti-VEGF drugs. The anti-angiogenic and anti-scarring dual action of RBM-007 holds promise as an additive or alternative therapy to anti-VEGF treatments for nAMD.

Results of switchback from ranibizumab to aflibercept in patients with exudative age-related macular degeneration.

PurposeIntravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection.MethodsEleven eyes of eleven patients were included in this study. Two patients were nonresponders, and nine exhibited tachyphylaxis to aflibercept. All patients received three monthly injections of ranibizumab as an initial phase of switching and received aflibercept as a switchback drug. We investigated changes in injection interval, visual acuity, and central retinal thickness.ResultsIn four patients (36.4%), injection interval was extended. The interval was 6.73 weeks before switch and 9.27 weeks after switchback (P=0.96). LogMAR visual acuity was 0.22 before switch and 0.24 after switchback (P=0.62). Central retinal thickness was 306.8 µm before switch and 256.1 after switchback (P=0.13). In all patients who were nonresponders to aflibercept, injection interval could not be extended.ConclusionA switchback from ranibizumab to aflibercept may be beneficial in some patients with AMD who exhibit tachyphylaxis to aflibercept.

Anti-Fumarase Antibody as a Predictor of Functional Efficacy of Anti-VEGF Therapy for Diabetic Macular Edema.

To evaluate whether baseline titers of anti-fumarase antibody are associated with visual prognosis after anti-VEGF treatment for diabetic macular edema (DME). In this retrospective study, we investigated 52 eyes of 52 DME patients who received intravitreal injections of anti-VEGF drugs (ranibizumab or aflibercept) after blood sampling at baseline. Optical coherence tomography (OCT) images were obtained at every monthly visit. The serum titer of anti-fumarase antibody at baseline was measured using ELISA. We evaluated the relationship between the titer of anti-fumarase antibody at baseline and visual acuity (VA) improvement at 12 months. The serum titer of anti-fumarase IgG was related to the logMAR visual acuity (VA; R = 0.329, P = 0.017) and the disrupted ellipsoid zone (EZ; R = 0.364, P = 0.008) at baseline. The titer of this autoantibody was not associated with logMAR VA (R = -0.007, P = 0.980) but was associated with VA improvement (R = 0.465, P < 0.001) at 12 months upon anti-VEGF treatment. The transverse length of the disrupted EZ line was shortened at 12 months (P < 0.001), and restoration of the EZ line was correlated to the autoantibody titer (R = 0.396, P = 0.004) compared with the decrease in central subfield (CSF) thickness. Multivariate analysis showed that pretreatment logMAR VA (β = 0.296, P = 0.045) and the autoantibody titer (β = 0.328, P = 0.017) were associated with VA improvement after anti-VEGF treatment. In contrast, the titer was not associated with logMAR VA at 12 months. Anti-fumarase antibody is a novel serum biomarker predicting better functional efficacy of anti-VEGF treatment for DME.

Electrophysiological study of the visual pathway in anti-VEGF therapy of neovascular age-related macular degeneration combined with glaucoma

To assess the effect of intravitreal administration of anti-VEGF drugs ranibizumab and aflibercept on the functional state of the visual pathway in patients with neovascular age-related macular degeneration (nAMD) and primary open-angle glaucoma (POAG) using the method of recording visual evoked potentials (VEP). A total of 54 patients (54 eyes) with nAMD and POAG were examined. The control group consisted of 39 healthy patients (39 eyes). The study included 24 patients (24 eyes) with stage IA POAG, 23 patients (23 eyes) with stage IIA POAG, 7 patients (7 eyes) with stage IIIA POAG. All patients with nAMD and POAG were given intravitreal injection of anti-VEGF drug: 35 patients received ranibizumab, 19 patients received aflibercept. Injections were performed monthly for 3 months. Ophthalmologic examination included visometry, biomicroscopy, retinal OCT using SPECTRALIS tomograph ('Heidelberg Engineering GmbH', Germany). VEP were recorded on EP-1000 Multifocal ('Tomey', Germany). All ophthalmologic studies were performed prior to administration of the anti-VEGF preparation and after the 3rd injection. After the third intravitreal injection of anti-VEGF drugs, best corrected visual acuity (BCVA) increased to 0.46±0.1 (p=0.001). According to OCT, central retinal thickness decreased by an average of 110.6 µm, the total volume of the retina decreased by 1.3 mm3, total thickness RNFL - by 3.8 µm (p<0.05). A decrease in the peak latency and an increase in the amplitude of the component P100 of VEP were noted. Statistically significant differences in indicators of VEP between antiangiogenic drugs ranibizumab and aflibercept were not detected (p>0.05). Intravitreal administration of anti-VEGF drugs ranibizumab and aflibercept has no negative influence on the functional state of the visual pathway in patients with nAMD and POAG. Intravitreal injections of ranibizumab and aflibercept can be considered a safe treatment option for patients with nAMD and POAG.

The efficacy and safety of aflibercept and conbercept in diabetic macular edema.

Diabetic macular edema (DME) has shown an increasing prevalence during the past years and is the leading cause of diabetic retinopathy blindness. Traditional treatment modalities include laser and corticosteroid therapy, which, however, either act through unclear mechanisms or cause cataracts and elevated intraocular pressure. In recent years, as the pathogenic role of VEGF in DME has been well-recognized, the intravitreal injection of anti-VEGF drugs has become the first-line treatment of DME due to their great efficacy in improving visual acuity and mitigating macular edema. Advantages have been shown for aflibercept and conbercept, the two recombinant decoy receptors that can bind VEGF with high specificity and affinity, in DME treatment in clinical trials conducted both worldwide and in People's Republic of China. This review introduces the structural characteristics and molecular mechanisms of action of these two anti-VEGF drugs, and summarizes the clinical trials evaluating their efficacy and safety, with the hope to provide clues for designing optimal and personalized therapeutic regimens for DME patients.

Влияние интравитреального введения anti-VEGF препаратов на показатели офтальмотонуса у пациентов с классическими и скрытыми хориоидальными неоваскулярными мембранами

Влияние интравитреального введения anti-VEGF препаратов на показатели офтальмотонуса у пациентов с классическими и скрытыми хориоидальными неоваскулярными мембранами

Clinical effect of vitreoretinal surgery combined with intravitreal injection of conbercept or ranibizumab on severe proliferative diabetic retinopathy

Background Vitreoretinal surgery (VRS) is the main treatment of severe proliferative diabetic retinopathy (PDR), intravitreal injection of anti-VEGF drugs before VRS on severe PDR has been widely used in clinic, but the auxiliary effect of different anti-VEGF drugs on VRS is unclear. Objective This study was to observe the efficacy of preoperative intravitreal injection of anti-VEGF drugs for the treatment of severe PDR, and to compare the efficacy of intravitreal conbercept (IVC) versus intravitreal ranibizumab (IVR) before VRS. Methods A retrospective, comparative study was performed.Niety-six severe PDR patients (98 eyes) who experienced VRS were collected in Tianjin Eye Institute from October 2014 to January 2016.There were 32 eyes in the preoperative IVC group, 31 eyes in the preoperative IVR group and 35 eyes in the simple VRS group.The intravitreal injection was performed 3 days prior to VRS in the preoperative IVC group and preoperative IVR group.All operations were conducted by the same physician.The duration of VRS, number of endodiathermy, incidence of severe hemorrhage and iatrogenic retinal breaks were recorded.The follow-up visit ranged from 3 to 6 months with an average of (3.51±0.59) months, the changes of best corrected visual acuity (BCVA) and incidence of postoperative complications were compared among the three groups. Results The average operation duration was (84.84±11.03) minutes and (83.45±14.24) minutes in the preoperative IVC group and preoperative IVR group respectively, which were significantly shorter than (104.57±13.42) minutes in the simple VRS group, with significant differences between them (t=6.622, 6.604, both at P 0.05). The mean BCVAs were significantly different among the 3 groups of different timepoints (Fgroup=4.077, P=0.020; Ftime=100.937, P=0.000). The postoperative mean BCVA at 3 months after surgery was (0.80±0.37), (0.82±0.32) and (1.03±0.52) in the preoperative IVC group, preoperative IVR group and simple VRS group respectively, which was significantly improved compared with preoperative results (all at P<0.01). The postoperative BCVAs were improved in preoperative IVC group and preoperative IVR group compared with the simple VRS group, with significant differences between them(both at P<0.05). Conclusions The preoperative intravitreal injection of anti-VEGF drugs combined with VRS is conductive to shorten the average operation time, reduce the rate of intraoperative hemorrhage, endodiathermy as well as improve the BCVA.Conbercept and ranibizumab had the similar auxiliary effect for VRS for the treatment of severe PDR. Key words: Proliferative diabetic retinopathy; Vascular endothelial growth factor; Conbercept; Ranibizumab; Vitreoretinal surgery

The Urokinase Receptor-Derived Peptide UPARANT Mitigates Angiogenesis in a Mouse Model of Laser-Induced Choroidal Neovascularization.

A mouse model of age-related macular degeneration (AMD) was used to investigate the anti-angiogenic and anti-inflammatory role of UPARANT in laser-induced choroidal neovascularization (CNV). Choroidal neovascularization was induced by laser photocoagulation, and UPARANT was intravitreally injected. Some experiments were also performed after either intravitreal injection of anti-VEGF drugs or systemic administration of UPARANT. Immunohistochemistry using CD31 antibodies was used to evaluate the area of CNV. Evans blue dye extravasation was quantitatively assessed. Transcripts of markers of outer blood retinal barrier were measured by quantitative RT-PCR, also used to evaluate angiogenesis and inflammation markers. Western blot was used to determine levels of transcription factors encoding genes involved in angiogenesis and inflammation. Levels of urokinase-type plasminogen activator (uPA), its receptor (uPAR), and formyl peptide receptors (FPRs) were determined at the transcript and the protein level. Intravitreal UPARANT reduced the CNV area and the leakage from the choroid. The uPA/uPAR/FPR system was upregulated in CNV, but was not influenced by UPARANT. UPARANT recovered laser-induced upregulation of transcription factors encoding angiogenic and inflammatory markers. Accordingly, angiogenic and inflammatory factors were also reduced. UPARANT as compared to anti-VEGF drugs displayed similar effects on CNV area. UPARANT mitigates laser-induced CNV by inhibiting angiogenesis and inflammation through an action on transcription factors encoding angiogenesis and inflammatory genes. The finding that UPARANT is effective against CNV may help to establish uPAR and its membrane partners as putative targets in the treatment of AMD.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease

IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

Effect and nursing on treatment of idiopathic choroidal neovascularization by intravitreal injection of anti-VEGF drugs

Objective To research the clinical efficacy and nursing on treatment of idiopathic choroidal neovascularization by intravitreal injection of anti-VEGF drugs. Methods From January 2011 to May 2013, a total of 36 cases of idiopathic choroidal neovascularization were given intravitreal injection of anti-VEGF drugs. Psychological care was used to eliminate patients′ tension and fear, and to establish the confidence of overcoming the disease. Preoperative and postoperative care and disease health guidance were given to patients. Results 36 patients had stable psychological state and could coordinate well with treatment and care. During the 8 to 96 weeks follow up, all patients′ vision had begun to improve after 1 week, and stabilized after 4 weeks. Conclusions Intravitreal injection of anti-VEGF treatment can subside choroidal neovascularization quickly, and improve vision rapidly, and significantly shorten the recovery course. Good psychological care of patients before surgery, enhancing patients′ postoperative care and health guidance could shorten the course of disease, and improved the quality of nursing service. Key words: Idiopathic choroidal neovascularization; Intravitreal injection; Vascular endothelial growth factor; Perioperative nursing

System review and meta-analysis on photodynamic therapy in central serous chorioretinopathy.

To evaluate the effect of photodynamic therapy (PDT) on central serous chorioretinopathy (CSC) compared with laser therapy and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, and to find the maximum treatment effect with minimal dose and fluence of PDT. A systematic electronic search was conducted in Feb 2013 in PubMed, Embase, ISI Web of Knowledge and the Cochrane library. The main outcome factors were compared in best-corrected visual acuity (BCVA), central macular thickness (CMT) and resolution of subretinal fluid (SRF). Meta-analysis was performed when it is appropriate. The comparisons were designed into four groups: group 1, PDT versus laser photocoagulation; group 2, PDT versus intravitreal injection of anti-VEGF drugs; group 3, half-dose verteporfin PDT versus placebo; group 4, half-fluence PDT versus full-fluence PDT. We retrieved nine reports of studies including a total of 319 patients. In group 1, the summary result indicated that PDT was superior in resolution of SRF (p = 0.005) than laser photocoagulation. In group 2, PDT could resolute SRF (p = 0.007) and decrease CMT (p = 0.002) more rapidly than intravitreal injection of anti-VEGF drugs. In group 3, half-dose PDT was effective in improving BCVA (p < 0.00001), decreasing CMT (p = 0.001) and resolving SRF (p < 0.001). In group 4, half-fluence PDT was effective and could significantly decrease the hypoxic damage which was caused by PDT (p < 0.001). PDT is a promising therapy for CSC patients and the parameters of PDT can be adjusted to obtain the maximum treatment effect with minimal adverse effects.

Effect of Prophylactic Medication and Influence of Vitreous Reflux in Pressure Rise after Intravitreal Injections of Anti-VEGF Drugs

To assess the efficacy of a hypotensive prophylactic medication in preventing intraocular pressure (IOP) changes after intravitreal injections, and the effect of occurrence of vitreous reflux on the variation of IOP. A total of 141 intravitreal injections of anti-vascular endothelial growth factor drugs (0.05 mL) were randomly distributed into 2 groups: in group 1 (n = 77), no prophylactic IOP-lowering medication was used; in group 2 (n = 64), a fixed combination of brimonidine and timolol was instilled 5 minutes before the injection. The IOP was measured before and 1, 15, and 30 minutes after the injection. The presence of vitreous reflux was recorded. Despite significantly reducing the IOP by ~3 mm Hg, prophylactic medication did not prevent a transient IOP rise. A total of 22.7% of injections showed vitreous reflux, and those patients experienced much lower initial spikes. Indeed, only 6.5% out of 77 injections above 30 mm Hg within 1 minute after injection showed vitreous reflux. Only one case showed an IOP >30 mm Hg at 15 minutes, and none at 30 minutes postinjection. The IOP normalization rates over time were similar in all groups within 15 minutes. Prophylactic medication instilled 5 minutes before the injection was not effective in preventing a pressure rise after intravitreal injections. Vitreous reflux decreased significantly the spike figures compared to injections with no reflux.

Correlation Between the Findings of Optical Coherent Retinal Tomography (OCT), Stereo Biomicroscopic Images from Fundus of an Eye and Values from Visual Acuity of Diabetic Macular Edema

Introduction:Diabetic maculopathy is the major cause of reduced visual acuity in patients with non-proliferative diabetic retinopathy and occurs on average in 29% of patients who have diabetes for 20 or more years.Aim:The aim of this study is to re examine the correlation between the findings of optical coherence retinal tomography, stereo bio-microscopic images from fundus of an eye and values from visual acuity of diabetic macular edema. In addition, the aim is to show the importance of various ophthalmic tests for establishing diagnosis in time.Material and methods:The research sample consisted of 90 subjects-patients from Cabinet for photographic documentation, fluorescein angiography and laser photocoagulation in Department of Ophthalmology at the University Clinical Centre in Sarajevo. The study was a one-year long, prospective, clinical study.Results:Research has shown a positive correlation between the various tests that are applied for the diagnosis of diabetic macular edema. Accurate and early diagnosis is of great importance for the treatment in time of this disease by applying laser photocoagulation, intravitreal injections of Anti-VEGF drugs or surgical treatment by Pars Plana Vitrectomy.

Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic diseases

Macular degeneration is the leading cause of blindness in developed countries. In the treatment of neovascular age-related macular degeneration, vascular endothelial growth factor (VEGF) has emerged as a key target for therapy. The intravitreal injection of anti-VEGF drugs has been widely employed to reduce the disease progression and improve the visual outcomes of the affected patients. However, each intravitreal inoculation poses a risk of several complications as infection, inflammation, endophthalmitis, intraocular inflammation, increase of intraocular pressure and vitreous hemorrhage. This short review evaluates the efficacy and the incidence of adverse drug reactions related to intravitreal administration of the main anti-VEGF drugs actually available: Bevacizumab, ranibizumab and aflibercept.

Influence of intravitreal avastin on the expression of cell factors in retinal proliferative membrane in proliferative diabetic retinopathy eye

Background A main cause of visual impairment in proliferative diabetic retinopathy (PDR) is vitreous hemorrhage and retinal detachment due to contraction of fibrovascular membrane.To explore the pathogenic mechanism of fibrovascular membrane is a new target for the prevention and management of PDR.Objective This study was to determine the change in expression of vascular endothelial growth factor (VEGF),connective tissue growth factor(CTGF) and pigment epithelium derived factor(PEDF) in the proliferative membranes of patients with PDR after intravitreal injection of avastin,an anti-VEGF agent.Methods This study was approved by the Medical Ethic Committee of Tianjin Medical College,and written informed consent was obtained from each patient before enrollment.A prospective randomized-controlled study was designed.Twenty-six eyes of 24 patients with PDR scheduled for surgery were enrolled from January to June,2008 in Tianjin Medical College Eye Hospital.The patients were randomized into the simple vitrectomy group and avastin injection combined with vitrectomy group,with matched gender,age and disease duration.1.25 mg (0.05 ml) of avastin was intravitreally injected prior to surgery,and vitrectomy was performed 10 days after injection in the avastin injection combined with vitrectomy group,and only vitrectomy was given in the simple vitrectomy group.Preretinal membrane was collected during the surgery.Expression of VEGF,CTGF and PEDF in the preretinal membranes was assayed by immunochemistry.Results VEGF,CTGF and PEDF were expressed in the cytoplasm.The rate of VEGF expression in the preretinal membranes was 30.77％ in the avastin injection combined with vitrectomy group,showing a significant reduction in comparison with the simple vitrectomy group(100.00％)(U =4.000,P＜0.01).The rate of expression CTGF was remarkable elevated in the avastin injection combined with vitrectomy group compared with the simple vitrectomy group (92.31％ vs.62.54％)(U=7.500,P=0.048).However,no significant difference was found in the expression rate of PEDF between the two groups(100.00％ vs.92.31％) (U =65.500,P =0.299).Conclusions The results suggest that intravitreal injection of anti-VEGF drugs resulted in the decrease of VEGF expression and increased CTGF expression in proliferative membranes from patients with PDR. Key words: Anti-vascular endothelial growth factor/avastin; Diabetic retinopathy; Retinal proliferative membrane; Vascular endothelial growth factor; Connective tissue growth factor; Pigment epithelium derived factor

Anti-Vascular Endothelial Growth Factor Agents for Ocular Angiogenesis and Vascular Permeability

Recent clinical trials regarding the intravitreal injection of antivascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, pegaptanib, and aflibercept) have shown excellent results in the treatment of angiogenic pathologies including choroidal neovascularization, macular edema, proliferative diabetic retinopathy, and neovascular glaucoma. Ranibizumab (Lucentis, Genectech, San Francisco), a fragment of a humanized monoclonal antibody against all VEGF isoforms, is beneficial in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD). Bevacizumab (Avastin, Genentech, San Francisco), a humanized, recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been approved as an adjuvant agent for the treatment of colorectal carcinoma and has also been increasingly used as an offlabel therapy in the field of ophthalmology. Pegaptanib (Mucugen, Pfizer, New York) is a 28-base ribonucleic acid aptamer, covalently linked to two branched 20-kD polyethylene glycol moieties, that was developed to bind and block the activity of extracellular VEGF, specifically the 165-aminoacid isoform (VEGF165). Aflibercept (VEGF Trap-Eye, Regeneron, New York; Bayer, Berlin, Germany) is a 115-kDa recombinant fusion protein consisting of the VEGF-binding domains of human VEGF receptors 1 and 2 fused to the Fc domain of human immunoglobulin-G1. Intraocular injections of anti-VEGF drug are considered to be an effective treatment for macular edema after retinal vein occlusion. The recent reports may lead to a shift in treatment paradigm for diabetic macular edema, from laser photocoagulation to newer approaches using anti-VEGF drugs. There have been several well-publicized prospective, randomized studies that demonstrated the efficacy of intravitreal injection of anti-VEGF drugs for patients with AMD. Adjuvant bevacizumab for neovascular glaucoma may prevent further peripheral anterior synechiae formation, and it is likely to open up a therapeutic window for a panretinal photocoagulation and trabeculectomy. Intravitreal injection of bevacizumab (IVB) results in a substantial decrease in bleeding from the retinal vessels or new vessels during a standard vitrectomy. IVB has also been reported to be effective for inducing the regression of new vessels in proliferative diabetic retinopathy. The use of bevacizumab in stage 4 or 5 retinopath of prematurity (ROP) is to reduce the plus sign to help reduce hemorrhage during the subsequent vitrectomy. Some authors reported cases of resolution of stage 4A ROP after bevacizumab injection. This special issue of anti-VEGF agents comprises five review articles and two research articles. The review article of K. Kimoto and T. Kubota is a concise overview on the application of anti-VEGF agents in angiogenic pathologies and vascular permeability. The review article of A. Willard and I. Herman describes the mechanisms behind diabetic retinal complications, current research supporting anti-VEGF medications, and future therapeutic directions. The review of P. Keane and S. Sadda summarizes the history of anti-VEGF drugs and presents a guide for clinicians on the development of anti-VEGF therapies for intraocular use. The review article of Y. Park et al. describes the treatment possibilities including combination therapy for age-related macular degeneration. The review article of I. Zampros et al. summarizes the current literature regarding the effectiveness of current anti-VEGF treatment for neovascular AMD. The two research articles describe (i) bevacizumab injection in patients with age-related macular degeneration associated with poor initial visual acuity, (ii) photodynamic therapy combined with intravitreal ranibizumab for exudative age-related macular degeneration. We sincerely hope that the present volume of a special issue series may provide useful information to understand the mechanisms of the clinical effects of anti-VEGF drug therapy, as well as the evaluation of their outcomes for the readers in Journal of Ophthalmology. Toshiaki Kubota Yoshiaki Kiuchi Carl Sheridan